Attention Deficit Hyperactivity Disorder (ADHD)

J ECT. 2005 Jun;21(2):88-95.

Transcranial magnetic stimulation in persons younger than the age of 18.

Quintana H.

Department of Psychiatry, Division of Child and Adolescent Psychiatry, Louisiana State University Health Science Center, School of Medicine, New Orleans, Louisiana 70112-2822, USA. Hquint@lsuhsc.edu

OBJECTIVES: To review the use of transcranial magnetic stimulation (single-pulse TMS, paired TMS, and repetitive TMS [rTMS]) in persons younger than the age of 18 years. I discuss the technical differences, as well as the diagnostic, therapeutic, and psychiatric uses of TMS/rTMS in this age group.

METHODS: I evaluated English-language studies from 1993 to August 2004 on nonconvulsive single-pulse, paired, and rTMS that supported a possible role for the use of TMS in persons younger than 18. Articles reviewed were retrieved from the MEDLINE database and Clinical Scientific index.

RESULTS: The 48 studies reviewed involved a total of 1034 children ages 2 weeks to 18 years; 35 of the studies used single-pulse TMS (980 children), 3 studies used paired TMS (20 children), and 7 studies used rTMS (34 children). Three studies used both single and rTMS. However, the number of subjects involved was not reported.

CONCLUSIONS: Single-pulse TMS, paired TMS, and rTMS in persons younger than 18 has been used to examine the maturation/activity of the neurons of various central nervous system tracts, plasticity of neurons in epilepsy, other aspects of epilepsy, multiple sclerosis, myoclonus, transcallosal inhibition, and motor cortex functioning with no reported seizure risk. rTMS has been applied to psychiatric disorders such as ADHD, ADHD with Tourette’s, and depression. Adult studies support an antidepressant effect from repetitive TMS, but there is only one study that has been reported on 7 patients that used rTMS to the left dorsal prefrontal cortex on children/adolescents with depression (5 of the 7 subjects treated responded). Although there are limited studies using rTMS (in 34 children), these studies did not report significant adverse effects or seizures. Repetitive TMS safety, ethical, and neurotoxicity concerns also are discussed.

Biol Psychiatry. 2005 Jun 15;57(12):1597-600.

Transcranial magnetic stimulation-evoked cortical inhibition: a consistent marker of attention-deficit/hyperactivity disorder scores in tourette syndrome.

Gilbert DL, Sallee FR, Zhang J, Lipps TD, Wassermann EM.

Division of Neurology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, OH 45229-3039, USA. d.gilbert@cchmc.org

BACKGROUND: Prior case-control studies using Transcranial Magnetic Stimulation (TMS) to probe the neural inhibitory circuitry of Attention Deficit Hyperactivity Disorder (ADHD), Tourette Syndrome (TS), and Obsessive Compulsive Disorder (OCD), have yielded conflicting results. Using regression analysis in TS patients with tics, ADHD, and/or OCD symptoms, all ranging from none to severe, we previously found that TMS-evoked short interval intracortical inhibition (SICI) correlated inversely with ADHD scores. We sought to validate this observation.

METHODS: We used regression to estimate the consistency of the association between ADHD symptom scores and TMS-evoked SICI at two separate visits in 28 children and adults with TS.

RESULTS: ADHD scores correlated significantly and consistently with SICI, particularly in patients not taking dopamine receptor blockers (r=.60 and r=.58). Hyperactivity, not inattention, scores accounted for ADHD-related variance in SICI.

CONCLUSIONS: SICI reliably reflects the severity of hyperactivity in children and adults with TS.

Child Adolesc Psychiatr Clin N Am. 2005 Jan;14(1):1-19, v.

Emerging brain-based interventions for children and adolescents: overview and clinical perspective.

Hirshberg LM, Chiu S, Frazier JA.

The NeuroDevelopment Center, 260 West Exchange Street, Suite 302, Providence, RI 02903, USA. lhirshberg@neruodevelopmentcenter.com

Electroencephalogram biofeedback (EBF), repetitive transcranial magnetic stimulation (rTMS), and vagal nerve stimulation (VNS) are emerging interventions that attempt to directly impact brain function through neurostimulation and neurofeedback mechanisms. This article provides a brief overview of each of these techniques, summarizes the relevant research findings, and examines the implications of this research for practice standards based on the guidelines for recommending evidence based treatments as developed by the American Academy of Child and Adolescent Psychiatry for attention deficit hyperactivity disorder (ADHD). EBF meets the “Clinical Guidelines” standard for ADHD, seizure disorders, anxiety, depression, and traumatic brain injury. VNS meets this same standard for treatment of refractory epilepsy and meets the lower “Options” standard for several other disorders. rTMS meets the standard for “Clinical Guidelines” for bipolar disorder, unipolar disorder, and schizophrenia. Several conditions are discussed regarding the use of evidence based thinking related to these emerging interventions and future directions.

Curr Med Res Opin. 2003;19(2):125-30.

Repetitive transcranial magnetic stimulation (rTMS): new tool, new therapy and new hope for ADHD.

Acosta MT, Leon-Sarmiento FE.

Department of Neurology, Children’s National Medical Center, Washington, DC, USA.

Attention-deficit hyperactivity disorder (ADHD) is the most common developmental disorder that is associated with environmental and genetic factors. Neurobiological evidence suggests that fronto-striatum-cerebellum circuit abnormalities, mainly in the right hemisphere, are responsible for most of the disturbed sensorimotor integration; dopamine seems to be the main neurochemical alteration underlying these morphological abnormalities. Different conventional treatments have been employed on ADHD; however, repetitive transcranial magnetic stimulation (rTMS), a new and useful option for the clinical/research investigation of several neuropsychiatric disorders involving dopamine circuits, has yet to be considered as a therapeutic tool and possible drug-free option for ADHD. Here the authors explore the available evidence that makes this tool a rational therapeutic possibility for patients with ADHD, calling attention to safety issues, while highlighting the potentials of such an approach and the new hope it may bring for patients, parents, researchers and clinicians. The authors advocate carefully conducted clinical trials to investigate efficacy, safety, cost-effectiveness and clinical utility of rTMS for ADHD patients – in comparison to both placebo and standard treatments.

Clin Neurophysiol. 2003 Nov;114(11):2036-42.

Disturbed transallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD).

Buchmann J, Wolters A, Haessler F, Bohne S, Nordbeck R, Kunesch E.

Department of Child and Adolescence Neuropsychiatry, Centre of Nerve Disease, University of Rostock, Gehlsdorfer Strasse 20, 18147 Rostock, Germany.

OBJECTIVE: The aim of this study was to investigate mechanisms of motor-cortical excitability and inhibition which may contribute to motor hyperactivity in children with attention deficit hyperactivity disorder (ADHD).

METHODS: Using transcranial magnetic stimulation (TMS), involvement of the motor cortex and the corpus callosum was analysed in 13 children with ADHD and 13 sex- and age-matched controls. Contralateral silent period (cSP) and transcallosally mediated ipsilateral silent period (iSP) were investigated.

RESULTS: Resting motor threshold (RMT), amplitudes of motor evoked potentials (MEP) and cSP were similar in both groups whereas iSP-latencies were significantly longer (p<0.05) and their duration shorter (p<0.01) in the ADHD group. For the ADHD group iSP duration tended to increase and iSP latency to decrease with age (n.s.). Conners-Scores did neither correlate with iSP-latencies and -duration nor with children’s age.

CONCLUSIONS: The shortened duration of iSP in ADHD children could be explained by an imbalance of inhibitory and excitatory drive on the neuronal network between cortex layer III-the projection site of transcallosal motor-cortical fibers-and layer V, the origin of the pyramidal tract. The longer iSP-latencies might be the result of defective myelination of fast conducting transcallosal fibers in ADHD. iSP may be a useful supplementary diagnostic tool to discriminate between ADHD and normal children.

J Child Neurol. 2001 Dec;16(12):891-4.

Subjective reactions of children to single-pulse transcranial magnetic stimulation.

Garvey MA, Kaczynski KJ, Becker DA, Bartko JJ.

Pediatric Movement Disorders Unit, Pediatrics and Developmental Neuropsychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1255, USA. garveym@intra.nimh.nih.gov

Single-pulse transcranial magnetic stimulation is a useful tool to investigate cortical function in childhood neuropsychiatric disorders. Magnetic stimulation is associated with a shock-like sensation that is considered painless in adults. Little is known about how children perceive the procedure. We used a self-report questionnaire to assess children’s subjective experience with transcranial magnetic stimulation. Normal children and children with attention-deficit hyperactivity disorder (ADHD) underwent transcranial magnetic stimulation in a study of cortical function in ADHD. Subjects were asked to rate transcranial magnetic stimulation on a 1 to 10 scale (most disagreeable = 1, most enjoyable = 10) and to rank it among common childhood events. Thirty-eight subjects completed transcranial magnetic stimulation; 34 said that they would repeat it. The overall rating for transcranial magnetic stimulation was 6.13, and transcranial magnetic stimulation was ranked fourth highest among the common childhood events. These results suggest that although a few children find transcranial magnetic stimulation uncomfortable, most consider transcranial magnetic stimulation painless. Further studies are necessary to confirm these findings.

Atrial Fibrillation

Heart Rhythm. 2015 Apr;12(4):809-17. doi: 10.1016/j.hrthm.2014.12.022. Epub 2014 Dec 19.

The use of low-level electromagnetic fields to suppress atrial fibrillation.

Yu L1, Dyer JW2, Scherlag BJ2, Stavrakis S2, Sha Y2, Sheng X2, Garabelli P2, Jacobson J3, Po SS4.

Author information

Abstract

BACKGROUND:

Extremely low-level electromagnetic fields have been proposed to cause significant changes in neural networks.

OBJECTIVE:

We sought to investigate whether low-level electromagnetic fields can suppress atrial fibrillation (AF).

METHODS:

In 17 pentobarbital anesthetized dogs, bilateral thoracotomies allowed the placement of multielectrode catheters in both atria and at all pulmonary veins. AF was induced by rapid atrial pacing (RAP) or programmed atrial extrastimulation. At baseline and end of each hour of RAP, during sinus rhythm, atrial programmed stimulation gave both the effective refractory period (ERP) and the width of the window of vulnerability. The latter was a measure of AF inducibility. Microelectrodes inserted into the anterior right ganglionated plexi recorded neural firing. Helmholtz coils were powered by a function generator inducing an electromagnetic field (EMF; 0.034 μG, 0.952 Hz). The study sample was divided into 2 groups: group 1 (n = 7)-application of EMF to both cervical vagal trunks; group 2 (n = 10)-application of EMF across the chest so that the heart was located in the center of the coil.

RESULTS:

In group 1, EMF induced a progressive increase in AF threshold at all pulmonary vein and atrial sites (all P < .05). In group 2, the atrial ERP progressively shortened and ERP dispersion and window of vulnerability progressively increased (P < .05 compared to baseline values) during 3 hours of RAP and then returned to baseline values during 3 hours of combined application of RAP and EMF (P < .05 compared to the end of the third hour of RAP). The frequency and amplitude of the neural activity recorded from the anterior right ganglionated plexi were markedly suppressed by EMF in both groups.

CONCLUSION:

Pulsed EMF applied to the vagal trunks or noninvasively across the chest can significantly reverse AF inducibility.

Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

Atrial fibrillation; Autonomic nervous system; Electromagnetic fieldPMID: 25533588 DOI: 10.1016/j.hrthm.2014.12.022

https://www.ncbi.nlm.nih.gov/pubmed/25533588

Atherosclerosis – Obliterating Vascular Disease

Adv Gerontol. 2015;28(1):68-71.

INFLUENCE OF MILLIMETER-WAVE ELECTROMAGNETIC EMISSION ON NITRIC OXIDE SYNTHESIS DURING VESSEL ENDOTHELIUM AGING IN VITRO.

[Article in Russian] Molodtsova ID, Medvedev DS, Poliakova VO, Lin’kova NS, Gurko GI. Abstract
The applying of millimeter-wave electromagnetic emission (EHF-therapy) is an effective method for various age-related pathologies treatment, among other cardio-vascular diseases. During the EHF-emission of aging human endothelial cell cultures it was obtained changing of NO-synthase (eNOS), endothelin-1, angiotensin-2 and vasopressin expression dependence of irradiation exposition. These data have shown that EHF-emission has activated endothelium functional activity, which can play the important role to search for approaches to treatment of arterial hypertension and atherosclerosis.

Biomed Pharmacother. 2005 Oct;59 Suppl 1:S174-6.

Effect of the alternative magnetic stimulation on peripheral circulation for regenerative medicine.

Yambe T, Inoue A, Sekine K, Shiraishi Y, Watanabe M, Yamaguchi T, Shibata M, Maruyama M, Konno S, Nitta S.

Department of Medical Engineering and Cardiology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-77, Japan. yambe@idac.tohoku.ac.jp

Abstract

Regenerative medicine for patients with peripheral atherosclerosis attracts considerable attention around the world. However, ethical problems persist in gene therapy. This study evaluates the effect of alterative magnetic stimulation on peripheral circulation. The effect of magnetic stimulation as a medical treatment was examined using a thermograph for 11 healthy volunteers. The thermograph was used to measure the rise in skin temperature. The experimental results suggested an improvement in the peripheral circulation. The results of our study suggest the effectiveness of alternative magnetic stimulation on atherosclerosis. We intend to extend our study in order to establish a methodology for regenerative medical treatment for patients with peripheral atherosclerosis. Further, we wish to advance the current research in the field of angiogenesis.

Vopr Kurortol Fizioter Lech Fiz Kult. 2000 Jul-Aug;(4):3-7.

Recovery processes in the cerebral cortex, myocardium and thymus of rats with experimental atherosclerosis exposed to low-frequency electromagnetic fields on the head.

[Article in Russian]

Zubkova SM, Varakina NI, Mikha?lik LV, Bobkova AS, Chabanenko SS, Luk’ianova TV.

Abstract

Studies of animals with experimental sclerosis has shown that a course of 10 procedures of alternative magnetic field (AMF) (50 Hz, 30 mT, 3 min daily) promotes partial recovery of the lipid spectrum and corrects vasomotor-metabolic disturbances in the cerebral cortex, myocardium and thymus caused by atherosclerosis. Combination of AMF with constant magnetic field in the same regime and location does not produce a hypolipidemic effect in atherosclerotic animals and this, in combination with increased vascular permeability may aggravate the condition. Activated microcirculation, antioxidant and antiproteinase effects in activation of biosynthetic processes in the cerebral cortex reflect inhibition in the CNS in this combined effect and create conditions for a hypotensive effect.

Vopr Kurortol Fizioter Lech Fiz Kult. 1998 Jul-Aug;(4):31-6.

The combined action of infrared radiation and permanent and alternating magnetic fields in experimental atherosclerosis.

[Article in Russian]

Zubkova SM, Varakina NI, Mikhailik LV, Bobkova AS, Maksimov EB.

Paravertebral exposure to infrared radiation (0.87 micron, 5 mW) and permanent magnetic field in combination with one- and two-semiperiodic alternative magnetic fields (50 Hz, 15-30 mT) was studied in respect to the action on adaptive reactions in animals with experimental atherosclerosis. Complex consisting of infrared radiation, permanent magnetic field and one-semiperiodic pulse alternative magnetic field was most effective in restoration of vasomotor-metabolic and immune disturbances accompanying development of atherosclerosis.

Vestn Khir Im I I Grek. 1996;155(5):37-9.

The potentials of laser and electromagnetic-laser therapy in the treatment of patients with arteriosclerosis obliterans of the vessels of the lower extremities.

[Article in Russian]

Galimzianov FV.

A comparative analysis of the laser and electromagnetic laser therapy was performed in the complex treatment of patients with obliterating atherosclerosis of the lower extremity vessels. Laser treatment exerts a therapeutic effect related with its influence upon microcirculation. The effectiveness of complex treatment becomes higher when using a combination of laser therapy with the impulse electromagnetic therapy of complex modulation at the expense of improvement of the regional blood circulation in all links of the vasculature.

Vopr Kurortol Fizioter Lech Fiz Kult. 1993 Sep-Oct;(5):22-5.

The use of magnetics and laser therapy in treating obliterating vascular diseases of the extremities.

[Article in Russian]

Kirillov IuB, Shval’b PG, Lastushkin AV, Sigaev AA, Kachinskii AE, Shashkova SN.

The paper presents the results of treatment received by 60 patients suffering from lower limb vascular obliteration stage IIA-III. The treatment involved combined use of magnetic field and laser irradiation. Peripheral circulation and central hemodynamics were evaluated rheographically and using ultrasound Doppler sphygmomanometry. Combined application of the above two modalities produced a greater effect on central hemodynamics compared to them introduced alone.

Vopr Kurortol Fizioter Lech Fiz Kult. 1992 May-Jun;(3):14-7.

Magnetotherapy in obliterating vascular diseases of the lower extremities.

[Article in Russian]

Kirillov IuB, Shval’b PG, Lastushkin AV, Baranov VM, Sigaev AA, Zueva GV, Karpov EI.

The investigators have developed a polymagnetic system “Avrora-MK-01” employing running impulse magnetic field to treat diseases of the leg vessels by the action on peripheral capillary bed. At a pregangrene stage a positive effect on peripheral capillaries was achieved in 75-82% of the patients treated.

Khirurgiia (Mosk). 1990 Nov;(11):41-3.

Outpatient electromagnetic therapy combined with hyperbaric oxygenation in arterial occlusive diseases.

[Article in Russian]

Reut NI, Kononova TI.

The authors first applied hyperbaric oxygenation (HBO) in the outpatient clinic in 1968. Barotherapy was conducted in 107 outpatients whose ages ranged from 27 to 80 years; they had various stages of the disease of 5- to 20-year history. In 70 patients treated for obliterating diseases of the vessels by HBO in a complex with magnetotherapy by means of magnetophors, the remission lasted 1-2 years; patients treated by HBO alone had a 3-8 month remission. A prolonged positive effect was produced in 64 patients. The suggested effective and safe method is an additional one to the existing means of treating this serious and progressive disease, which can be applied successfully in outpatient clinics.

Asthma

Vopr Kurortol Fizioter Lech Fiz Kult. 2007 Sep-Oct;(5):24-6.

Infitatherapy of children with bronchial asthma

[Article in Russian]

Konova OM, Markarov GS, Zaslavski? AIu.

Abstract

Use of nonmedicamental methods of treatment assists to improve the control of children’s bronchial asthma clinical course. Pulsed low-frequency electromagnetic field regulates the state of central and vegetative nervous system and improves psychological status of child. Inphytotherapy has bronchial spasmolytic and immune correction effects.

Acta Physiol Hung. 2003;90(4):327-34.

The effect of the pulsatile electromagnetic field in children suffering from bronchial asthma.

Sadlonova J, Korpas J, Salat D, Miko L, Kudlicka J.

Ist Internal Clinic, Teaching Hospital Martin, Martin, Slovakia. sadlonova@jfmed.uniba.sk

From the bibliography it is well known that pulsatile electromagnetic field has an anti-inflammatory and analgesic effect. It causes vasodilatation, myorelaxation, hyper-production of connective tissue and activation of the cell membrane. Therefore our aim was to study the possible therapeutic effect of pulsatile electromagnetic field in asthmatic children. Forty-two children participating in this study were divided in two groups. The 1st group consisting of 21 children (11 females, 10 males, aged 11.8 +/- 0.4 yr) was treated by pulsatile electromagnetic field and pharmacologically. The 2nd group served as control, consisting also of 21 children (11 females, 10 males, aged 11.7 +/- 0.3 yr) and was treated only pharmacologically. Therapeutic effect of the pulsatile electromagnetic field was assessed on the basis of pulmonary tests performed by means of a Spirometer 100 Handi (Germany). The indexes FVC, IVC, ERV, IRV, FEV1, FEV1/FVC%, MEF75,50,25, PEF, PIF and the changes of the flow-volume loop were also registered. The pulsatile electromagnetic field was applied by means of the device MTU 500H, Therapy System (Brno, Czech Republic) for 5 days, two times daily for 30 minutes (magnetic induction: 3 mT, frequency: 4 Hz as recommended by the manufacturer). The results in children of the 1st group showed an improvement of FVC of about 70 ml, IVC of about 110 ml, FEV1 of about 80 ml, MEF75 of about 30 ml, PEF of about 480 ml, PIF of about 550 ml. The increases of ERV, IRV and FEV1/FVC and decreases of MEF25,50 were statistically insignificant. The results in the 2nd group were less clear. The flow-volume loop showed a mild improvement in 14 children. This improvement in the 2nd group was less significant. The clinical status of children and their mood became better. We believe that the pulsatile electro-magnetotherapy in children suffering from asthma is effective. On the basis of our results we can recommend it as a complementary therapy.

Bratisl Lek Listy. 2002;103(7-8):260-5.

The effect of the pulsatile electromagnetic field in patients suffering from chronic obstructive pulmonary disease and bronchial asthma.

Sadlonova J, Korpas J, Vrabec M, Salat D, Buchancova J, Kudlicka J.

Department of Internal Medicine, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia. sadlonova@jfmed.uniba.sk

Abstract

Pulsatile electromagnetotherapy (PETh) stimulates biological tissues and processes; it modulates ion exchange across cell membranes and thus regulates the tone of smooth muscles. On the basis of these effects we hypothetized that PETh might treat COPD and bronchial asthma. We examined 117 (61 females, 56 males) adult patients who were decided in 4 groups. The 1st consisted of 16 patients with COPD who were treated by PETh and pharmacologically. The 2nd group (control) consisted of 24 patients with COPD who were treated only with medicaments. The 3rd group consisted of 37 asthmatics, treated by PETh and medicaments. The 4th group (control) consisted of 40 asthmatics treated only with medicaments. The effectiveness of PETh was assessed by lung function tests, which were performed using a Spirometer 100 Handi (Germany). We measured FVCex, FEV1, percentage of FEV1/FVCex, MEF25, 50, 75, PEF and registered the flow-volume loops. PETh was applied by apparatus MTU 500H (Therapy System, Czech Republic). It was administered 10 doses; once daily for 20 min, with a frequency of 4.5 Hz and a magnetic induction 3 T. The initial 3 doses were about 25% lower then the later doses. PETh was very effective in patients with COPD. The measured indexes improved about 200-660 ml or ml x s(-1), except FVC. PETh was less effective in asthmatics. Most indices improved without statistical significance, about 50-620 ml or ml x s(-1). The indices of FEV1/FVC and MEF25 deteriorated. The changes in controls without PETh were very small. (Tab. 2, Fig. 1, Ref. 19.)

Bratisl Lek Listy. 2000;101(2):71-7.

The sensitivity of tussinphonography for assessing the effectiveness of treatment.

Korpas J, Salat D, Sadlonova J, Vrabec M, Kudlicka J.

Department of Pathophysiology, Jessenius Medical School Martin, Slovakia.

Our previous studies have demonstrated that tussiphonogram is suitable not only for the detection of pathological condition in the respiratory tract but also for treatment effectiveness assessment. The purpose of this study was to evaluate the possibilities of tussiphonography in detection of already little pathological changes in the airways and lungs. Therefore the changes of voluntary cough sound indexes were compared with pulmonary function tests in selected group of asthmatics before and after a pulsatile electromagnetic therapy in which the effect of therapy on pulmonary function tests was minimal. After magnetotherapy in 18 patients with increased expiratory forced lung capacity by 7.3% and increased peak inspiratory flow by 31.7% in average the voluntary cough sound intensity decreased by 37.8%, the sound duration shortened by 11% and the sound pattern showed the tendency to normalization. The improvement of mentioned cough indexes was absent in 17 patients who were treated by magnetotherapy too, but at the same time suffered from respiratory viral infection and in 22 patients treated only with climatotherapy and antiasthmatics. Changes of flow-volume loops in patients were not in the close relation to other followed indices. The correlation analysis showed a functional connection in relative differences of cough sound indices and some pulmonary function tests. The results confirmed the suitability of tussiphonography to indicate even mild pathological changes in respiratory tract. (Fig. 4, Ref. 21.)

Vopr Kurortol Fizioter Lech Fiz Kult. 1996 Mar-Apr;(2):13-5.

The rehabilitative treatment of children with bronchial asthma

[Article in Russian]

Alymkulov DA, To?chieva FM, Saralinova GM, Le?kina LF.

Abstract

Staged regimen of decimetric wave electromagnetic therapy and microclimate of high altitude salt mines were used in sanatorium treatment of children with bronchial asthma. Pretreatment with the above magnetic field induced positive changes in the reflex-segmental zone which reflected in better adaptation to the high altitude climate. The latter promoted beneficial rearrangement of respiratory function and cardiovascular system.

Vopr Kurortol Fizioter Lech Fiz Kult. 1995 Nov-Dec;(6):16-8.

The efficacy of using an electromagnetic field of extremely high frequency (54-78 GHz) in treating patients with chronic nonspecific lung disease.

[Article in Russian]

Danilenko SR, Shatrov AA, Gerasimovich OI.

Abstract

After a trial of the therapeutic complex including extra high frequency electromagnetic field in 154 patients with chronic bronchitis and bronchial asthma high efficacy of EHF-therapy was stated in the above diseases.

Vopr Kurortol Fizioter Lech Fiz Kult. 1994 May-Jun;(3):6-10.

A validation for the combined transcerebral exposure to a UHF electrical field and to decimeter waves in the area of the splenic projection in bronchial asthma.

[Article in Russian]

Maliavin AG, Rychkova MA, Nikoda NV.

Abstract

Thirty patients with bronchial asthma of moderate severity in unstable remission were treated with transcerebral UHF electric field and decimeter waves on the spleen region. Clinical and laboratory postexposure findings provided evidence in favour of the regimens used. Tolerance of the procedures, comparative efficacy regarding the clinico-pathogenetic variant, probable mechanisms of therapeutic action are discussed.

Arthritis – Rheumatoid

Tissue Eng Part B Rev. 2018 Apr;24(2):144-154. doi: 10.1089/ten.TEB.2017.0294. Epub 2017 Nov 17.

Pulsed Electromagnetic Fields and Tissue Engineering of the Joints.

Iwasa K1, Reddi AH1.

Author information

1 Department of Orthopaedic Surgery, Lawrence Ellison Center for Tissue Regeneration and Repair, School of Medicine, University of California , Davis, Davis, California.

Abstract

BACKGROUND:

Bone and joint formation, maintenance, and regeneration are regulated by both chemical and physical signals. Among the physical signals there is an increasing realization of the role of pulsed electromagnetic fields (PEMF) in the treatment of nonunions of bone fractures. The discovery of the piezoelectric properties of bone by Fukada and Yasuda in 1953 in Japan established the foundation of this field. Pioneering research by Bassett and Brighton and their teams resulted in the approval by the Food and Drug Administration (FDA) of the use of PEMF in the treatment of fracture healing. Although PEMF has potential applications in joint regeneration in osteoarthritis (OA), this evolving field is still in its infancy and offers novel opportunities.

METHODS:

We have systematically reviewed the literature on the influence of PEMF in joints, including articular cartilage, tendons, and ligaments, of publications from 2000 to 2016.

CONCLUSIONS:

PEMF stimulated chondrocyte proliferation, differentiation, and extracellular matrix synthesis by release of anabolic morphogens such as bone morphogenetic proteins and anti-inflammatory cytokines by adenosine receptors A2A and A3 in both in vitro and in vivo investigations. It is noteworthy that in clinical translational investigations a beneficial effect was observed on improving function in OA knees. However, additional systematic studies on the mechanisms of action of PEMF on joints and tissues therein, articular cartilage, tendons, and ligaments are required.

KEYWORDS:

PEMF; articular cartilage; regeneration

Rheumatol Int. 2010 Mar;30(5):571-86. Epub 2009 Oct 30.

Complementary and alternative medicine use in rheumatoid arthritis: proposed mechanism of action and efficacy of commonly used modalities.

Efthimiou P, Kukar M.

Rheumatology Division, Lincoln Medical and Mental Health Center, Weill Cornell Medical College, 234 E. 149th Street, New York, NY 10451, USA. petrosefthimiou@gmail.com

Abstract

Complementary and alternative medicine (CAM) has become popular in patients with rheumatoid arthritis (RA) worldwide. The objective of this study is to systematically review the proposed mechanisms of action and currently available evidence supporting the efficacy of CAM modalities in relieving signs and symptoms of RA. The prevalence of CAM usage by RA patients is anywhere from 28% to 90%. Many published studies on CAM are based on animal models of RA and there is often insufficient evidence for the efficacy of CAM modalities in RA. The existing evidence suggests that some of the CAM modalities, such as acupuncture, herbal medicines, dietary omega-3 fatty acids, vitamins, and pulsed electromagnetic field show promising efficacy in reducing pain. While the use of CAM modalities for the treatment of RA continues to increase, rigorous clinical trials examining their efficacy are necessary to validate or refute the clinical claims made for CAM therapies.

Indian J Exp Biol.  2009 Dec;47(12):939-48.

Low frequency pulsed electromagnetic field–a viable alternative therapy for arthritis.

Ganesan K, Gengadharan AC, Balachandran C, Manohar BM, Puvanakrishnan R.

Source

Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai 600 020, India.

Abstract

Arthritis refers to more than 100 disorders of the musculoskeletal system. The existing pharmacological interventions for arthritis offer only symptomatic relief and they are not definitive and curative. Magnetic healing has been known from antiquity and it is evolved to the present times with the advent of electromagnetism. The original basis for the trial of this form of therapy is the interaction between the biological systems with the natural magnetic fields. Optimization of the physical window comprising the electromagnetic field generator and signal properties (frequency, intensity, duration, waveform) with the biological window, inclusive of the experimental model, age and stimulus has helped in achieving consistent beneficial results. Low frequency pulsed electromagnetic field (PEMF) can provide noninvasive, safe and easy to apply method to treat pain, inflammation and dysfunctions associated with rheumatoid arthritis (RA) and osteoarthritis (OA) and PEMF has a long term record of safety. This review focusses on the therapeutic application of PEMF in the treatment of these forms of arthritis. The analysis of various studies (animal models of arthritis, cell culture systems and clinical trials) reporting the use of PEMF for arthritis cure has conclusively shown that PEMF not only alleviates the pain in the arthritis condition but it also affords chondroprotection, exerts antiinflammatory action and helps in bone remodeling and this could be developed as a viable alternative for arthritis therapy.

Life Sci. 2007 Jun 6;80(26):2403-10. Epub 2007 May 1.

Low frequency and low intensity pulsed electromagnetic field exerts its antiinflammatory effect through restoration of plasma membrane calcium ATPase activity.

Selvam R, Ganesan K, Narayana Raju KV, Gangadharan AC, Manohar BM, Puvanakrishnan R.

Department of Pharmacology and Toxicology, Madras Veterinary College, Vepery, Chennai, India.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting 1% of the population worldwide. Pulsed electromagnetic field (PEMF) has a number of well-documented physiological effects on cells and tissues including antiinflammatory effect. This study aims to explore the antiinflammatory effect of PEMF and its possible mechanism of action in amelioration of adjuvant induced arthritis (AIA). Arthritis was induced by a single intradermal injection of heat killed Mycobacterium tuberculosis at a concentration of 500 microg in 0.1 ml of paraffin oil into the right hind paw of rats. The arthritic animals showed a biphasic response regarding changes in the paw edema volume. During the chronic phase of the disease, arthritic animals showed an elevated level of lipid peroxides and depletion of antioxidant enzymes with significant radiological and histological changes. Besides, plasma membrane Ca(2+) ATPase (PMCA) activity was inhibited while intracellular Ca(2+) level as well as prostaglandin E(2) levels was noticed to be elevated in blood lymphocytes of arthritic rats. Exposure of arthritic rats to PEMF at 5 Hzx4 microT x 90 min, produced significant antiexudative effect resulting in the restoration of the altered parameters. The antiinflammatory effect could be partially mediated through the stabilizing action of PEMF on membranes as reflected by the restoration of PMCA and intracellular Ca(2+) levels in blood lymphocytes subsequently inhibiting PGE(2) biosynthesis. The results of this study indicated that PEMF could be developed as a potential therapy for RA in human beings.

Pain Res Manag. 2006 Summer;11(2):85-90.

Exposure to a specific pulsed low-frequency magnetic field: a double-blind placebo-controlled study of effects on pain ratings in rheumatoid arthritis and fibromyalgia patients.

Shupak NM, McKay JC, Nielson WR, Rollman GB, Prato FS, Thomas AW.

Lawson Health Research Institute, St. Joseph’s Health Care, London, Ontario N6A 4V2.

Abstract

BACKGROUND: Specific pulsed electromagnetic fields (PEMFs) have been shown to induce analgesia (antinociception) in snails, rodents and healthy human volunteers.

OBJECTIVE: The effect of specific PEMF exposure on pain and anxiety ratings was investigated in two patient populations.

DESIGN: A double-blind, randomized, placebo-controlled parallel design was used.

METHOD: The present study investigated the effects of an acute 30 min magnetic field exposure (less than or equal to 400 microTpk; less than 3 kHz) on pain (McGill Pain Questionnaire [MPQ], visual analogue scale [VAS]) and anxiety (VAS) ratings in female rheumatoid arthritis (RA) (n=13; mean age 52 years) and fibromyalgia (FM) patients (n=18; mean age 51 years) who received either the PEMF or sham exposure treatment.

RESULTS: A repeated measures analysis revealed a significant pre-post-testing by condition interaction for the MPQ Pain Rating Index total for the RA patients, F(1,11)=5.09, P<0.05, estimate of effect size = 0.32, power = 0.54. A significant pre-post-effect for the same variable was present for the FM patients, F(1,15)=16.2, P<0.01, estimate of effect size = 0.52, power =0.96. Similar findings were found for MPQ subcomponents and the VAS (pain). There was no significant reduction in VAS anxiety ratings pre- to post-exposure for either the RA or FM patients.

CONCLUSION: These findings provide some initial support for the use of PEMF exposure in reducing pain in chronic pain populations and warrants continued investigation into the use of PEMF exposure for short-term pain relief.

Acupunct Electrother Res. 2003;28(1-2):11-8.

Treatment of rheumatoid arthritis with electromagnetic millimeter waves applied to acupuncture points–a randomized double blind clinical study.

Usichenko TI, Ivashkivsky OI, Gizhko VV.

Anesthesiology & Intensive Care Medicine Department, University of Greifswald, Germany. taras@uni-greifswald.de

Abstract

The aim of the study was to evaluate the efficacy and safety of electromagnetic millimeter waves (MW) applied to acupuncture points in patients with rheumatoid arthritis (RA). Twelve patients with RA were exposed to MW with power 2.5 mW and band frequency 54-64 GHz. MW were applied to the acupuncture points of the affected joints in a double blind manner. At least 2 and maximum 4 points were consecutively exposed to MW during one session. Total exposure time consisted of 40 minutes. According to the study design, group I received only real millimeter wave therapy (MWT) sessions, group II only sham sessions. Group III was exposed to MW in a random cross-over manner. Pain intensity, joint stiffness and laboratory parameters were recorded before, during and immediately after the treatment. The study was discontinued because of beneficial therapeutic effects of MWT. Patients from group I (n=4) reported significant pain relief and reduced joint stiffness during and after the course of therapy. Patients from group II (n=4) revealed no improvement during the study. Patients from group III reported the changes of pain and joint stiffness only after real MW sessions. After further large-scale clinical investigations MWT may become a non-invasive adjunct in therapy of patients with RA.

Neurosci Lett. 2001 Aug 17;309(1):17-20.

A comparison of rheumatoid arthritis and fibromyalgia patients and healthy controls exposed to a pulsed (200 microT) magnetic field: effects on normal standing balance.

Thomas AW, White KP, Drost DJ, Cook CM, Prato FS.

The Lawson Health Research Institute, Department of Nuclear Medicine & MR, St. Joseph’s Health Care, 268 Grosvenor Street, London, N6A 4V2, Ontario, Canada. athomas@lri.sjhc.london.on.ca

Specific weak time varying pulsed magnetic fields (MF) have been shown to alter animal and human behaviors, including pain perception and postural sway. Here we demonstrate an objective assessment of exposure to pulsed MF’s on Rheumatoid Arthritis (RA) and Fibromyalgia (FM) patients and healthy controls using standing balance. 15 RA and 15 FM patients were recruited from a university hospital outpatient Rheumatology Clinic and 15 healthy controls from university students and personnel. Each subject stood on the center of a 3-D forceplate to record postural sway within three square orthogonal coil pairs (2 m, 1.75 m, 1.5 m) which generated a spatially uniform MF centered at head level. Four 2-min exposure conditions (eyes open/eyes closed, sham/MF) were applied in a random order. With eyes open and during sham exposure, FM patients and controls appeared to have similar standing balance, with RA patients worse. With eyes closed, postural sway worsened for all three groups, but more for RA and FM patients than controls. The Romberg Quotient (eyes closed/eyes open) was highest among FM patients. Mixed design analysis of variance on the center of pressure (COP) movements showed a significant interaction of eyes open/closed and sham/MF conditions [F=8.78(1,42), P<0.006]. Romberg Quotients of COP movements improved significantly with MF exposure [F=9.5(1,42), P<0.005] and COP path length showed an interaction approaching significance with clinical diagnosis [F=3.2(1,28), P<0.09]. Therefore RA and FM patients, and healthy controls, have significantly different postural sway in response to a specific pulsed MF.

Arch Phys Med Rehabil. 2001 Oct;82(10):1453-60.

Two configurations of static magnetic fields for treating rheumatoid arthritis of the knee: a double-blind clinical trial.

Segal NA, Toda Y, Huston J, Saeki Y, Shimizu M, Fuchs H, Shimaoka Y, Holcomb R, McLean MJ.

Vanderbilt University Medical School, Nashville, TN 37232, USA.

Abstract

OBJECTIVE: To assess the efficacy of a nonpharmacologic, noninvasive static magnetic device as adjunctive therapy for knee pain in patients with rheumatoid arthritis (RA).

DESIGN: Randomized, double-blind, controlled, multisite clinical trial.

SETTING: An American and a Japanese academic medical center as well as 4 community rheumatology and orthopedics practices.

PATIENTS: Cohort of 64 patients over age 18 years with rheumatoid arthritis and persistent knee pain, rated greater than 40/100mm, despite appropriate use of medications.

INTERVENTION: Four blinded MagnaBloc (with 4 steep field gradients) or control devices (with 1 steep field gradient) were taped to a knee of each subject for 1 week.

MAIN OUTCOME MEASURES: The American College of Rheumatology recommended core set of disease activity measures for RA clinical trials and subjects’ assessment of treatment outcome.

RESULTS: Subjects randomly assigned to the MagnaBloc (n = 38) and control treatment groups (n = 26) reported baseline pain levels of 63/100mm and 61/100mm, respectively. A greater reduction in reported pain in the MagnaBloc group was sustained through the 1-week follow-up (40.4% vs 25.9%) and corroborated by twice daily pain diary results (p < .0001 for each vs baseline). However, comparison between the 2 groups demonstrated a statistically insignificant difference (p < .23). Subjects in the MagnaBloc group reported an average decrease in their global assessment of disease activity of 33% over 1 week, as compared with a 2% decline in the control group (p < .01). After 1 week, 68% of the MagnaBloc treatment group reported feeling better or much better, compared with 27% of the control group, and 29% and 65%, respectively, reported feeling the same as before treatment (p < .01).

CONCLUSIONS: Both devices demonstrated statistically significant pain reduction in comparison to baseline, with concordance across multiple indices. However, a significant difference was not observed between the 2 treatment groups (p < .23). In future studies, the MagnaBloc treatment should be compared with a nonmagnetic placebo treatment to characterize further its therapeutic potential for treating RA. This study did elucidate methods for conducting clinical trials with magnetic devices.

J Indian Med Assoc. 1998 Sep;96(9):272-5.

A study of the effects of pulsed electromagnetic field therapy with respect to serological grouping in rheumatoid arthritis.

Ganguly KS, Sarkar AK, Datta AK, Rakshit A.

National Institute for the Orthopaedically Handicapped (NIOH), Calcutta.

The positive role of pulsed electromagnetic field (PEMF) therapy in rheumatoid arthritis (RA) is known. The differential role of serological status of patients in RA is also well known. This paper presents a study of the differential effects of PEMF therapy on the two serological groups of patients. The responses of the seropositive patients are found to be more subdued. Varying effects of the therapy in alleviating the different symptomatologies indicate that the rheumatoid factor (RF) is more resistant to PEMF.

Eur J Clin Chem Clin Biochem. 1994 Apr;32(4):319-26.

Influence of electromagnetic fields on the enzyme activity of rheumatoid synovial fluid cells in vitro.

Mohamed-Ali H, Kolkenbrock H, Ulbrich N, Sorensen H, Kramer KD, Merker HJ.

Institut fur Anatomie, Freie Universitat Berlin, Germany.

Since positive clinical effects have been observed in the treatment of rheumatoid arthritis with electromagnetic fields of weak strength and low frequency range (magnetic field strength: 70 microT; frequency: 1.36-14.44 Hz), an attempt was made to analyse the effects of these electromagnetic fields on enzyme activity in monolayer cultures of rheumatoid synovial fluid cells after single irradiation of the cultures for 24 hours. We only investigated the matrix metalloproteinases (collagenase, gelatinase, proteinase 24.11 and aminopeptidases). It was found that electromagnetic fields of such a weak strength and low frequency range do not generally have a uniform effect on the activity of the different proteinases in vitro. While aminopeptidases do not show any great changes in activity, the peptidases hydrolysing N(2,4)-dinitrophenyl-peptide exhibit a distinct increase in activity in the late phase in culture medium without fetal calf serum. In the presence of fetal calf serum this effect is not observed and enzyme activity is diminished. Our experiments do not show whether such a phase-bound increase in the activity of proteinases in vitro is only one finding in a much broader range of effects of electromagnetic fields, or whether it is a specific effect of weak pulsed magnetic fields of 285 +/- 33 nT on enzyme activity after single irradiation. This question requires further elucidation.

Vopr Kurortol Fizioter Lech Fiz Kult. 1992 Jul-Aug;(4):9-13.

The combined action of an ultrahigh-frequency electrical field bitemporally and decimeter waves on the thymus area in the combined therapy of rheumatoid arthritis patients.

[Article in Russian]

Sidorov VD, Grigor’eva VD, Pershin SB, Bobkova AS, Korovkina EG.

Abstract

The thymus of rheumatoid arthritis (RA) patients was exposed to combined action of bitemporal UHF electric field and decimeter waves to study immunomodulating effect of the combination. Biochemical, immunological and endocrinological findings during the patients follow-up gave evidence for conclusion on activation of the hypothalamic-hypophyseal-thymic axis. A response was achieved in RA seronegative variant with concomitant synovitis. This may be due to genetic factors.

Arthritis – Osteoarthritis

Tissue Eng Part B Rev. 2018 Apr;24(2):144-154. doi: 10.1089/ten.TEB.2017.0294. Epub 2017 Nov 17.

Pulsed Electromagnetic Fields and Tissue Engineering of the Joints.

Iwasa K1, Reddi AH1.

Author information

1 Department of Orthopaedic Surgery, Lawrence Ellison Center for Tissue Regeneration and Repair, School of Medicine, University of California , Davis, Davis, California.

Abstract

BACKGROUND:

Bone and joint formation, maintenance, and regeneration are regulated by both chemical and physical signals. Among the physical signals there is an increasing realization of the role of pulsed electromagnetic fields (PEMF) in the treatment of nonunions of bone fractures. The discovery of the piezoelectric properties of bone by Fukada and Yasuda in 1953 in Japan established the foundation of this field. Pioneering research by Bassett and Brighton and their teams resulted in the approval by the Food and Drug Administration (FDA) of the use of PEMF in the treatment of fracture healing. Although PEMF has potential applications in joint regeneration in osteoarthritis (OA), this evolving field is still in its infancy and offers novel opportunities.

METHODS:

We have systematically reviewed the literature on the influence of PEMF in joints, including articular cartilage, tendons, and ligaments, of publications from 2000 to 2016.

CONCLUSIONS:

PEMF stimulated chondrocyte proliferation, differentiation, and extracellular matrix synthesis by release of anabolic morphogens such as bone morphogenetic proteins and anti-inflammatory cytokines by adenosine receptors A2A and A3 in both in vitro and in vivo investigations. It is noteworthy that in clinical translational investigations a beneficial effect was observed on improving function in OA knees. However, additional systematic studies on the mechanisms of action of PEMF on joints and tissues therein, articular cartilage, tendons, and ligaments are required.

KEYWORDS:

PEMF; articular cartilage; regeneration

Logo of ijortho

Indian J Orthop. 2016 Jan-Feb; 50(1): 87–93. doi:  10.4103/0019-5413.173522 PMCID: PMC4759881

Low dose short duration pulsed electromagnetic field effects on cultured human chondrocytes: An experimental study

Selvam Anbarasan, Ulaganathan Baraneedharan,1 Solomon FD Paul, Harpreet Kaur, Subramoniam Rangaswami,2 andEmmanuel Bhaskar3 Department of Human Genetics, Sri Ramachandra University, Porur, Chennai, Tamil Nadu, India 1Department of Biomedical Sciences, Sri Ramachandra University, Porur, Chennai, Tamil Nadu, India 2Department of Orthopaedics, Sri Ramachandra University, Porur, Chennai, Tamil Nadu, India 3Department of General Medicine, Sri Ramachandra University, Porur, Chennai, Tamil Nadu, India Address for correspondence: Mr. Selvam Anbarasan, Department of Human Genetics, Sri Ramachandra University, Porur, Chennai, Tamil Nadu, India. E-mail: moc.liamg@ivakbna Author information Copyright and License information Copyright : © Indian Journal of Orthopaedics This is an open access article distributed under the terms of the Creative Commons Attribution NonCommercial ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non commercially, as long as the author is credited and the new creations are licensed under the identical terms.

Abstract

Background:

Pulsed electromagnetic field (PEMF) is used to treat bone and joint disorders for over 30 years. Recent studies demonstrate a significant effect of PEMF on bone and cartilage proliferation, differentiation, synthesis of extracellular matrix (ECM) and production of growth factors. The aim of this study is to assess if PEMF of low frequency, ultralow field strength and short time exposure have beneficial effects on in-vitro cultured human chondrocytes.

Materials and Methods:

Primary human chondrocytes cultures were established using articular cartilage obtained from knee joint during joint replacement surgery. Post characterization, the cells were exposed to PEMF at frequencies ranging from 0.1 to 10 Hz and field intensities ranging from 0.65 to 1.95 ?T for 60 min/day for 3 consecutive days to analyze the viability, ECM component synthesis, proliferation and morphology related changes post exposure. Association between exposure doses and cellular effects were analyzed with paired’t’ test.

Results:

In-vitro PEMF exposure of 0.1 Hz frequency, 1.95 ?T and duration of 60 min/day for 3 consecutive days produced the most favorable response on chondrocytes viability (P < 0.001), ECM component production (P< 0.001) and multiplication. Exposure of identical chondrocyte cultures to PEMFs of 0.65 ?T field intensity at 1 Hz frequency resulted in less significant response. Exposure to 1.3 ?T PEMFs at 10 Hz frequency does not show any significant effects in different analytical parameters.

Conclusions:

Short duration PEMF exposure may represent a new therapy for patients with Osteoarthritis (OA).Keywords: Human chondrocytes, osteoarthritis, pulsed electromagnetic field MeSh terms: Osteoarthritis, cartilage, articular, chondrocytes, electromagnetic fields

Introduction

Pulsed electromagnetic field (PEMF) has been used to treat bone and joint disorders for over 30 years.1Clinical use of PEMF preceded systematic research in its utility for bone and joint healing.2 Later studies identified that PEMF is capable of producing significant cellular changes in bone and cartilage cells by proliferation, differentiation, synthesis of extracellular matrix (ECM) and production of growth factors.3,4,5,7,8,9,10 A systematic review based on 3 clinical studies which assessed effect of PEMF therapy for osteoarthritis (OA) of knee, incorporating factors like pain, physical function, patient assessment, joint imaging, health related quality of life and physician global assessment indicates that electrical stimulation therapy may be useful in OA of knee, but stresses the need for confirmation in future studies.11 Proteoglycan (PG) loss occurs in joint cartilage in OA and PEMF therapy has been shown to induce PG synthesis in-vivoand in-vitro.12 PEMF has also demonstrated to have positive effect on cellular proliferation and DNA synthesis through opening of voltage sensitive calcium channels.13 Animal models have shown that PEMF therapy retards progression of OA.14,15

Most studies employing PEMF have used frequencies of 6- 75 Hz and field strengths of 0.4- 2.3 milli Tesla (mT). We desired to enquire if low frequency (0.1- 10 Hz), low field strength of 0.65- 1.95 µT and short duration exposure (60 min/day) of PEMF results in favorable effects on cultured human chondrocytes (synthesis of ECM; cell viability, proliferation and morphology). Further need for the study is to arrive at a minimal PEMF exposure protocol that is expected to decrease the concern related to unfavorable cellular changes and chromosomal aberrations that may result with high dose PEMF exposure.16

Materials and Methods

Isolation and characterization of chondrocytes

Articular cartilage samples were obtained from knee joint during joint replacement surgery after obtaining informed consent from patients. The study protocol was approved by Institutional Ethics Committee. Cartilage tissue over the nonweight bearing portion of the joint was removed and minced in Dulbecco’s modified eagle medium (DMEM) (Biogene technologies, India) supplemented with 10% FBS (Biogene technologies, India) and 1 ml Pen-strep (10000 units of penicillin and 10 mg of streptomycin, Invitrogen, India). Following this, the tissue was transferred into a conical flask and initially digested with pronase (1 mg/ml) (Biogene technologies, India) for 60 min, followed by type II collagenase (1 mg/1ml) (Invitrogen) for 16- 18 hours at 37°C. The following day, cellular debris and undigested tissue were removed and cells were separated using a 100 micron cell strainer. Isolated cells were seeded into 25 cm 2 culture flasks (TPP, India) with DMEM complete medium and maintained at 37°C with 5% CO2 levels. The cells were subcultured on attainment of 80% confluency. The attached cells were characterized by chondrocyte specific anti-Sox 9 transcription factor antibody staining (Abcam, India.). Chondrocytes that failed to form monolayer culture were not processed further. Post characterization, 4 × 105 cells were seeded in each flask and used for PEMF exposure after first passage.

Pulsed electromagnetic field exposure

The PEMF coil system fashioned for exposure is a four member coil frames, two larger (inner) and two smaller (outer) coil frames. The coils are mounted coaxially and in a co-planar fashion to form an enclosure, where it delivers currents in milliamps at desired waveforms, varying frequencies and magnetic field strength (Madras Institute of Magnetobiology, Chennai, India). This system designed according to the parametrical equation of Fansleau and Brauenbeck and a modified version of the Helmhotz coil. A box is housed inside the coil in which a 100 W bulb with regulator was used to maintain the temperature at 37°C and water to maintain humidity. Instead of 5% CO2, 20 mM HEPES was used as a buffering system. The chondrocytes were exposed to PEMF while monitoring field strength, frequency and temperature. The control (unexposed) cells were placed in the same environment and temperature but not exposed to PEMF.

Pulsed electromagnetic field treatment

The chondrocytes were seeded in 25 cm 2 culture flasks at concentrations of 6.5 × 105 cells/ml after 20 h being plated the cells were washed with phosphate buffer saline (PBS), and given fresh medium and exposed to PEMF for the first three daily trials; media was not changed from this point onwards. PEMF at a frequency of 0.1, 1 and 10 Hz were applied with flux densities of 0.65, 1.3 and 1.95 µT (peak-to-peak) for 60 min/day for 3 consecutive days. Whereas exposure to PEMFs at a repetition rate of 0.1 and 1 Hz with 1.95 and 0.65 µT caused a significant increase in chondrocyte viability that was dependent on PEMF amplitude, PEMFs applied at a repetition rate of 10 Hz and 1.3 µT did not produce any noticeable effects over cell viability and were not dealt with further in this manuscript. To test for effects of different exposure durations, cells were exposed to PEMFs of 1.95 and 0.65 µT magnitude and at frequency of 0.1 and 1 Hz for 60 min/day for 3 days. Cells were analyzed on third day for further experimental studies.

Cell viability assessment

Chondrocytes were cultured in 96 well plates at a density of 5 × 103 cells per well and exposed to PEMF in accordance to the exposure protocol mentioned. Twenty microliter of 0.5% 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (Invitrogen) in phosphate buffered saline was added to each well after removal of medium and cells were incubated for 3 h at 37°C. Post incubation, 150 µl dimethyl sulfoxide (Hi-media, India) was added to each well and absorbance values (optical density value) were noted at 570 nm and 695 nm in spectrophotometer.17

Quantitative measurement of extracellular matrix proteoglycan and glycosaminoglycan synthesis

Chondrocytes were cultured in 48 well plates at densities of 104 cells per well and exposed to PEMF in accordance to the exposure protocol mentioned. Postexposure, glycosaminoglycan (GAG) synthesis was quantified by the dimethyl methylene blue (DMMB) assay. The DMMB reagent (Sigma, India) was prepared as detailed by Panin et al.18 and 200 µL was added to each well after removal of culture medium. Subsequently, absorbance values at 525 nm were noted.

Analysis of cell cycle by flow cytometry

Chondrocytes were cultured in 25 cm 2 culture flasks and exposed to PEMFs as mentioned earlier. After exposure, the cells were trypsinized, converted to single cell suspension in PBS and subjected to flow cytometery (FACS calibur, Becton Dickinson, Germany) according to the manufacturer’s instruction (Invitrogen, India) as follows: The suspension was spun at 1000 rpm for 10 min and the cell pellet was fixed in 70% ice cold ethanol at 4°C overnight. The cells were washed with PBS, treated with 500 µl RNAse A (40 µg/ml) (Sigma, India.) for 30 min at 37°C and stained with 500 µl propidium iodide (40 µg/ml) for 15 min incubation at room temperature. Postincubation, cell distributions at distinct phases of the cell cycle were analyzed by flow cytometery.

Analysis of cell architecture and morphology

Cell architecture and morphology were analyzed by staining of actin filaments in chondrocytes. Chondrocytes were cultured on cover slips in 6 well culture plates and exposed to PEMFs as described earlier. Processing of cells was done according to the manufacturer’s instructions (Invitrogen, India.). Briefly, the cells were fixed in 3.7% formaldehyde solution for 10 min after washing the slide with PBS and permeabilized in 0.1% Triton X-100 for 5 min. After washing with PBS, the cells were stained with 0.05 mg/ml Phalloidin solution at room temperature for 20-30 min, followed by counterstaining with 300 µl Propidium Iodide (500 nM). The coverslips were then rinsed in PBS, placed on a glass slide and cellular architecture and stress fiber formation was qualitatively analyzed by fluorescent confocal microscopy (LSM 510 META, Carl Zeiss, Germany).

Statistical analysis

Discrete variables were expressed as number (%) and continuous variables expressed as mean ± Standard Deviation. Association between field strengths (0.65, 1.3, and 1.95 µT) in variable frequencies (0.1, 1, and 10 Hz) and cellular effects (cell viability and ECM production,) was analyzed with paired ‘t’ test. A P < 0.05 was considered as statistically significant. Analysis was done with Statistical Package for the social sciences (SPSS) software version 21.0. This software was released in 2012 and used to solve business and research problems by means of ad-hoc analysis, hypothesis testing and predictive analysis.

Results

Isolation of chondrocytes

Healthy chondrocytes were observed in cultures by 3 days and these monolayers were 80% confluent by a week. The chondrocytes were spherical prior to attachment and later appeared polygonal in shape [Figure 1].

Figure 1

Figure 1 Primary human chondrocytes displaying typical polygonal conformation after attachment

Cell viability assessment

Viability of chondrocytes after PEMF exposure was quantified by the MTT assay to ascertain the effects PEMFs on chondrocytes which were exposed to PEMFs of field intensities between 1.95 and 0.65 µT at frequencies of 0.1 and 1 Hz for 60 min/day for 3 days. Following the third day exposure, samples were treated with MTT to quantify the cell viability and compared to control (unexposed) cultures. A highly significant viability of chondrocyte was observed in following field intensities and frequencies (1.95 µT-0.1Hz [P < 0.001], 1.95 µT -1Hz [P < 0.001] and 0.65 µT-0.1 Hz [P < 0.001]). Moderate favourable response was observed in other field intensities and frequencies [Table 1]. After 3 days of 60 min daily exposure to 1.95 µT PEMFs at a frequency of 0.1 Hz, the total number of cells in the culture increased, indicating heightened viability in response to PEMFs.

Table 1

Table 1 MTT assay for detection of viable cells after exposure to PEMFs for 3 consecutive days

Quantitative measurement of proteoglycan glycosaminoglycan synthesis

Our spectrophotometric quantification of the ECM components such as GAG and PGs were assayed with identical PEMF parameters (field strengths, frequencies, and days of exposure and duration of exposure) as those used for MTT assay of cell viability with identical results. As compared with previously observed results, favorable responses to the production of ECM components were seen in following field strengths and frequencies (1.95 µT-0.1 Hz [P < 0.001], 1.95 µT -1 Hz [P < 0.001], 0.65 µT-0.1 Hz [P < 0.001], 0.65 µT-1 Hz [P < 0.001], 1.95 µT-10 Hz [P = 0.001] and 0.65 µT-10 Hz [P = 0.001]. Moderate favorable response was observed in other field intensities and frequencies [Table 2]. Our spectrophotometric quantification thus corroborates and strengthen our MTT assay results, indicating that exposure with 1.95 µT field intensity at frequency of 0.1 Hz for 60 min/day was most effective in production of GAG and PG of chondrocytes.

Table 2

Table 2 DMMB assay for detection of ECM components after exposure to PEMFs for 3 consecutive days

Cell cycle analysis

Cells were analyzed to assess their distribution at different phases of the cell cycle by flow cytometry after staining of DNA with propidium iodide and recording of 106 events for each exposure parameter. The cells distribution in four distinct phases could be recognized in a proliferating cell population: G1, S (DNA synthesis Phase), G2 and M (Mitosis). As both G2 and M phase have an identical DNA content, they could not be discriminated based on their differences in their DNA content. The percentage values were assigned to each population and also dot plot [Figure ?[Figure2a2a and ?andb]b] and histogram [Figure ?[Figure2c2c and ?andd]d] were used to denote the distribution of cells in distinct phases. PEMF at different field strengths and frequencies was found to promote cell cycle progression from the G1 phase to the S and G2-M phases. Cells present in G2-M phase are in dividing state and show increased rate of proliferation. A shift to top of cell population (G2-M) in dot plot shows great proliferation [Figure ?[Figure2a2a and ?andb].b]. Based on the percentage of cells distribution in G2-M phase, proliferation effect was determined at different exposure parameters. Histogram indicates, cells exposed at 0.1 Hz frequency with 1.95 µT of PEMFs show 20.24% of their significant presence in G2-M phase compared to other filed strengths such as 0.65 (18.9%) and 1.3 µT (17.54%) [Figure 2c]. The cells exposed to 1.95 µT of PEMFs at 0.1 Hz frequency shows 20.24% of their significant presence in G2-M phase compared to other frequencies such as 1 Hz (19.46%) and 10 Hz (17.83%) [Figure 2d].

Figure 2

Figure 2 Cell cycle analysis by flow cytometer to determine the proliferative effect of chondrocytes in distinct cell cycle phases. Percentage of chondrocytes distribution in G2-M phase indicates cell proliferation effects as it has all mitotic cells. Significant

Analysis of cell architecture and morphology

Actin filaments of the cytoplasm stained by Phalloidin and nucleus was counterstained with propidium iodide observed by confocal fluorescent microscopy showed a significant difference in morphological structure and formation of stress fibers between exposed chondrocytes at varying frequencies (0.1, 1 and, 10 Hz) with specific field strength 1.95 µT and unexposed cells. Stress fiber formation was increased in chondrocytes exposed at frequency of 0.1 Hz with 1.95 µT compared to unexposed [Figure 3]. Stress fiber formation indicates that the cells stability, strength and their healthy attachment.

Figure 3

Figure 3 Human chondrocytes morphological structure was studied by staining with phalloidin and propidium iodide for visualizing stress fibers (green) and nuclear staining (red). (a) No stress fiber formation in chondrocytes unexposed to pulsed electromagnetic

Discussion

Our study observed that short term in-vitro chondrocyte exposure to PEMFs at frequency of 0.1 Hz and field strength of 1.95 µT for 60 min/day for 3 consecutive days have shown highly significant effects in different experimental parameters such as cell viability, ECM production, cell cycle progression and stress fiber formation. By contrast, exposure of identical chondrocyte cultures to PEMFs of 0.65 µT field intensity at 1 Hz frequency resulted in less significant levels of different parameters. On the other hand, exposure to 1.3 µT PEMFs at 10 Hz frequency does not shown any significant effects in different analytical parameters. These findings, apart from observing benefits of certain range of field strengths, also bring to light the ability of PEMF to inhibit cellular effects when used at certain field strengths and frequencies, a fact which has been observed earlier.

In our study design, we limited our experiments to within 3 days of exposure to PEMF to stay within the realm of better clinical applicability. For our analysis, we have chosen 3 days as an appropriate end point as it avoided the over confluence of chondrocytes and also it would minimize the contact inhibition that can induce changes in biochemical status and cause dedifferentiation. As the number of days of exposure to PEMFs increases, it may enhance the proliferative effects to the chondrocytes. The design of longer day exposure to PEMFs will be taken into future study. PEMF parameters used in this study such as frequency, field strength and duration of exposure could translate into the clinical application and will be innocuous to the target tissue and their surrounding tissues which are exposed to PEMF during clinical therapy.

Our study observed correlation between critical cell characteristics (cell viability and promotion in cell multiplication) of exposed samples and induction of extracellular components which include GAG and PG. This raises the question on the validity of using changes in ECM components as a marker of chondrocyte healing in studies using in-vitro models.

The earliest in-vitro study with bovine articular chondrocytes exposed using Helmholtz coils found no significant effect of PEMF on ECM component synthesis.19 Sakai and colleagues studied the effect of 0.4 mT field strength at 6.4 Hz delivered over a period of 5 days on rabbit growth cartilage and human articular cartilage and observed that PEMF stimulated cell proliferation and GAG synthesis in growth cartilage cells but resulted in only cell proliferation with no increase in GAG content in articular cartilage cells.20 The latter finding of our observation on extracellular components (GAG and PG) synthesis is comparable with earlier studies observation.

De Mattei et al. exposed chondrocytes from healthy patients to PEMF to varying duration of exposure (1- 18 h and 1- 6 days) using a field strength of 2.3 mT at 75 Hz. The study observed that short duration of exposure (1 and 6 h) did not result in increased DNA synthesis, while longer duration of exposure (9 and 18 h) increased DNA synthesis.21 Chang et al., exposed porcine chondrocytes to a field of 1.8- 3 mT at a frequency of 75 Hz for 2 h/day for 3 weeks and observed that long term 3 weeks PEMF exposure was beneficial over the short term 1 week exposure.22 However, our observations contradict these findings and reports the better efficacy of even short term PEMF exposures. Though our study observed the efficacy of a daily PEMF exposure of 60 min for only 3 days, benefits of exposure should be expected to enhance with daily exposures exceeding 3 days. We could not observe the benefits beyond day 3, since confluent chondrocyte cultures de-differentiated due to contact inhibition beyond this period in two-dimensional cultures.

Our observation on promotion of cell cycle from G1 phase to G2-M phase with certain field strengths is comparable with the findings of Nicolin et al. which observed similar results with field strength of 2 mT at 75 Hz with an exposure time of 4 h or 12 h/day.23 The striking observation of similar findings in our study with much lower field strength for exposure duration of 60 min has better clinical applicability.

A recent in-vivo animal study exposed rabbits with experimental osteochondral defect to PEMF for a period of 60 min/day for 6 weeks and observed a better total histological score in the study group to conclude that PEMF is beneficial for hyaline cartilage formation.24 The only in-vitro study on human chondrocytes harvested from OA knee reports no effect on PG production using field strength of 2mT at 50 Hz for 14 days.25 However both studies did not evaluate fine cellular effects (cell viability and cell cycle promotion).

Based on our data, the study informs that the future in-vitro studies on the topic should probably use exposure duration not more than 60 min/day but we can increase more number of days to PEMFs at 0.1 and 1 Hz frequencies and 1.95 and 0.65 µT field intensities. However, future studies should aim to utilize collagen matrix in three-dimensional (3D) cultures and focus more on exposure for more number of days to overcome the limitation of dedifferentiation and contact inhibition due to over confluent in 3D model and also focus on the effect of PEMF on chondrocyte cytoskeleton (observed as stress fibers in Phalloidin staining). It would of interest to investigate the strength of the chondrocyte cytoskeleton between exposed and control cells. Though it may be argued that occurrence of stress fiber formation observed with PEMF exposure is a result of heating effect due to Helmholtz system, the low dose of PEMF is less likely to have produced a heating effect which may happen with higher doses.

To conclude, our study observed that short duration (60 min/day) low frequency (0.1 Hz) low field strength (1.95 µT) PEMFs have beneficial effects on chondrocyte viability, ECM production, multiplication and probably cytoskeleton even for a short period of 3 days. Short duration PEMF exposure for patients with OA has the potential to produce favorable clinical effects. However, the results of the study have to be confirmed with a methodology incorporating assessment of both mass and strength of PEMF exposed chondrocytes.

Financial support and sponsorship

Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organisation (DRDO), Ministry of Defence, Government of India.

Conflicts of interest

There are no conflicts of interest.

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Millimeter wave treatment promotes chondrocyte proliferation via G1/S cell cycle transition.

Li X, Ye H, Yu F, Cai L, Li H, Chen J, Wu M, Chen W, Lin R, Li Z, Zheng C, Xu H, Wu G, Liu X.

Source

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, P.R. China.

Abstract

Millimeter waves, high-frequency electromagnetic waves, can effectively alleviate the clinical symptoms in osteoarthritis patients, as a non-pharmaceutical and non-invasive physical therapy regimen. However, the molecular mechanisms of the therapeutic effects of millimeter wave treatment are not well understood. In the present study, the effect of millimeter waves on the G1/S cell cycle progression in chondrocytes and the underlying mechanism was investigated. Chondrocytes isolated from the knee of SD rats were cultured and identified using toluidine blue staining. The second generation chondrocytes were collected and stimulated with or without millimeter waves for 48 h. Chondrocyte viability was analyzed using the MTT assay. The cell cycle distribution of chondrocytes was analyzed by flow cytometry. mRNA and protein expression levels of cyclin D1, cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) and p21 were detected using real-time PCR and western blotting, respectively. Millimeter wave stimulation was found to significantly enhance chondrocyte viability. Moreover, the percentage of chondrocytes in the G0/G1 phase was significantly decreased, whereas that in the S phase was significantly increased. In addition, following millimeter wave treatment, cyclin D1, CDK4 and CDK6 expression was significantly upregulated, whereas p21 expression was significantly downregulated. The results indicate that millimeter wave treatment promotes chondrocyte proliferation via cell cycle progression.

Vopr Kurortol Fizioter Lech Fiz Kult.  2010 Jul-Aug;(4):20-2.

The use of magnetic-laser therapy in the combined treatment of osteoarthrosis in workers exposed to inorganic fluoride compounds.

[Article in Russian]

Fedorov AA, Riabko EV, Gromov AS.

Abstract

The present study included 67 patients who had been exposed to the impact of inorganic fluoride compounds. It demonstrated beneficial effect of magnetolaser therapy in combination with whole body iodine-bromide-sodium chlorine baths, physical exercises, and massage on clinical manifestations of the primary disease and concomitant pathologies. Simultaneously, metabolic processes in the articular cartilage and bone tissue were normalized, lipid peroxidation was improved and optimization of antioxidative protection achieved. These changes are indicative of high therapeutic efficiency of the combined treatment employed in this study and its favourable influence on the quality of life of the patients.

Indian J Exp Biol. 2009 Dec;47(12):939-48.

Low frequency pulsed electromagnetic field–a viable alternative therapy for arthritis.

Ganesan K, Gengadharan AC, Balachandran C, Manohar BM, Puvanakrishnan R.

Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai 600 020, India.

Abstract

Arthritis refers to more than 100 disorders of the musculoskeletal system. The existing pharmacological interventions for arthritis offer only symptomatic relief and they are not definitive and curative. Magnetic healing has been known from antiquity and it is evolved to the present times with the advent of electromagnetism. The original basis for the trial of this form of therapy is the interaction between the biological systems with the natural magnetic fields. Optimization of the physical window comprising the electromagnetic field generator and signal properties (frequency, intensity, duration, waveform) with the biological window, inclusive of the experimental model, age and stimulus has helped in achieving consistent beneficial results. Low frequency pulsed electromagnetic field (PEMF) can provide noninvasive, safe and easy to apply method to treat pain, inflammation and dysfunctions associated with rheumatoid arthritis (RA) and osteoarthritis (OA) and PEMF has a long term record of safety. This review focusses on the therapeutic application of PEMF in the treatment of these forms of arthritis. The analysis of various studies (animal models of arthritis, cell culture systems and clinical trials) reporting the use of PEMF for arthritis cure has conclusively shown that PEMF not only alleviates the pain in the arthritis condition but it also affords chondroprotection, exerts antiinflammatory action and helps in bone remodeling and this could be developed as a viable alternative for arthritis therapy.

J Rehabil Med. 2009 Nov;41(13):1090-5.

Effect of biomagnetic therapy versus physiotherapy for treatment of knee osteoarthritis: a randomized controlled trial.

Gremion G, Gaillard D, Leyvraz PF, Jolles BM.

Department of Orthopaedic Surgery (DAL), Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.

Abstract

OBJECTIVE: To assess the effectiveness of pulsed signal therapy in the treatment of knee osteoarthritis (Kellgren II or III).

METHODS: A randomized, double-blind controlled clinical trial. The first 95 patients sent to the clinic with knee osteo-arthritis were selected and randomized into treatment with pulsed signal therapy or conventional physiotherapy. Assessment included recording of usual demographic data, pertinent history, baseline medication and radiographs. Clinical evaluation was made at baseline, 6 weeks and 6 months after the end of treatment by the same blinded doctor. At each follow-up time, the patient was asked to complete a visual analogue pain scale and a Lequesne score. The doctor recorded the degree of pain on motion and the ability to move the affected knee.

RESULTS: Both treatments resulted in significant improvements in pain and physical function. A statistical difference was observed only for activities of daily living, where the physiotherapy was more efficient (p<0.03). The cost of treatment with pulsed signal therapy was significantly higher, double the treatment cost of conventional physiotherapy.

CONCLUSION: Like physiotherapy, pulsed signal therapy has improved the clinical state of treated patients but with no significant statistical difference. Pulsed signal therapy is, however, more expensive.

J Rehabil Med. 2009 May;41(6):406-11.

Effectiveness of pulsed electromagnetic field therapy in the management of osteoarthritis of the knee: a meta-analysis of randomized controlled trials.

Vavken P, Arrich F, Schuhfried O, Dorotka R.

Department of Orthopedic Surgery, Children’s Hospital Boston, 300 Longwood Avenue, Enders 1016, Boston, MA 02115, USA. Patrick.vavken@childrens.harvard.edu

Abstract

OBJECTIVE: To assess the effectiveness of pulsed electromagnetic fields compared with placebo in the management of osteoarthritis of the knee.

DATA SOURCES: A systematic review of PubMed, EMBASE, and the Cochrane Controlled Trials Register.

METHODS: Randomized, controlled trials reporting on the blinded comparison of pulsed electromagnetic fields with placebo were included. Validity was tested according to the Jadad Scale. Studies were pooled using fixed-effects and random-effects models after exclusion of publication bias and assessment of heterogeneity. Sensitivity analyses and meta-regression were performed to test the stability of our findings.

RESULTS: Nine studies, including 483 patients, were pooled. No significant difference could be shown for pain (weighted mean difference 0.2 patients; 95% confidence interval (CI): -0.4 to 0.8) or stiffness (weighted mean difference 0.3; 95% CI: -0.3 to 0.9). There was a significant effect on activities of daily living (weighted mean difference 0.8; 95% CI 0.2-1.4, p = 0.014) and scores (standardized mean difference 0.4; 95% CI: 0.05-0.8, p = 0.029). We saw only statistically insignificant differences between studies with different treatment protocols.

CONCLUSION: Pulsed electromagnetic fields improve clinical scores and function in patients with osteoarthritis of the knee and should be considered as adjuvant therapies in their management. There is still equipoise of evidence for an effect on pain in the current literature.

Rheumatol Int. 2009 Apr;29(6):663-6. Epub 2008 Nov 18.

The effects of pulsed electromagnetic fields in the treatment of knee osteoarthritis: a randomized, placebo-controlled trial.

Ay S, Evcik D.

Department of Physical Medicine and Rehabilitation, Ufuk University School of Medicine Doctor Ridvan Ege Hospital, Balgat, 06520, Ankara, Turkey.saimeay@yahoo.com

Abstract

In this study, we planned to investigate the effects of pulse electromagnetic field (PEMF) on pain relief and functional capacity of patients with knee osteoarthritis (OA). Fifty-five patients with knee OA were included in a randomized, placebo-controlled study. At the end of the therapy, there was statistically significant improvement in pain scores in both groups (P < 0.05). However, no significant difference was observed within the groups (P > 0.05). We observed statistically significant improvement in some of the subgroups of Lequesne index. These are morning stiffness and activities of daily living activities compared to placebo group. However, we could not observe statistically significant differences in total of the scale between two groups (P > 0.05). Applying between-group analysis, we were unable to demonstrate a beneficial symptomatic effect of PEMF in the treatment of knee OA in all patients. Further studies using different types of magnetic devices, treatment protocols and patient populations are warranted to confirm the general efficacy of PEMF therapy in OA and other conditions.

Knee Surg Sports Traumatol Arthrosc. 2007 Jul;15(7):830-4. Epub 2007 Feb 28.

Effects of pulsed electromagnetic fields on patients’ recovery after arthroscopic surgery: prospective, randomized and double-blind study.

Zorzi C, Dall’Oca C, Cadossi R, Setti S.

“Sacro Cuore Don Calabria” Hospital, Via don A. Sempreboni 5, 37024 Negrar (Vr), Italy.

Abstract

Severe joint inflammation following trauma, arthroscopic surgery or infection can damage articular cartilage, thus every effort should be made to protect cartilage from the catabolic effects of pro-inflammatory cytokines and stimulate cartilage anabolic activities. Previous pre-clinical studies have shown that pulsed electromagnetic fields (PEMFs) can protect articular cartilage from the catabolic effects of pro-inflammatory cytokines, and prevent its degeneration, finally resulting in chondroprotection. These findings provide the rational to support the study of the effect of PEMFs in humans after arthroscopic surgery. The purpose of this pilot, randomized, prospective and double-blind study was to evaluate the effects of PEMFs in patients undergoing arthroscopic treatment of knee cartilage. Patients with knee pain were recruited and treated by arthroscopy with chondroabrasion and/or perforations and/or radiofrequencies. They were randomized into two groups: a control group (magnetic field at 0.05 mT) and an active group (magnetic field of 1.5 mT). All patients were instructed to use PEMFs for 90 days, 6 h per day. The patients were evaluated by the Knee injury and Osteoarthritis Outcome Score (KOOS) test before arthroscopy, and after 45 and 90 days. The use of non-steroidal anti-inflammatory drugs (NSAIDs) to control pain was also recorded. Patients were interviewed for the long-term outcome 3 years after arthroscopic surgery. Thirty-one patients completed the treatment. KOOS values at 45 and 90 days were higher in the active group and the difference was significant at 90 days (P < 0.05). The percentage of patients who used NSAIDs was 26% in the active group and 75% in the control group (P = 0.015). At 3 years follow-up, the number of patients who completely recovered was higher in the active group compared to the control group (P < 0.05). Treatment with I-ONE aided patient recovery after arthroscopic surgery, reduced the use of NSAIDs, and also had a positive long-term effect.

Life Sci. 2007 Jun 6;80(26):2403-10. Epub 2007 May 1.

Low frequency and low intensity pulsed electromagnetic field exerts its antiinflammatory effect through restoration of plasma membrane calcium ATPase activity.

Selvam R, Ganesan K, Narayana Raju KV, Gangadharan AC, Manohar BM, Puvanakrishnan R.

Department of Pharmacology and Toxicology, Madras Veterinary College, Vepery, Chennai, India.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting 1% of the population worldwide. Pulsed electromagnetic field (PEMF) has a number of well-documented physiological effects on cells and tissues including antiinflammatory effect. This study aims to explore the antiinflammatory effect of PEMF and its possible mechanism of action in amelioration of adjuvant induced arthritis (AIA). Arthritis was induced by a single intradermal injection of heat killed Mycobacterium tuberculosis at a concentration of 500 microg in 0.1 ml of paraffin oil into the right hind paw of rats. The arthritic animals showed a biphasic response regarding changes in the paw edema volume. During the chronic phase of the disease, arthritic animals showed an elevated level of lipid peroxides and depletion of antioxidant enzymes with significant radiological and histological changes. Besides, plasma membrane Ca(2+) ATPase (PMCA) activity was inhibited while intracellular Ca(2+) level as well as prostaglandin E(2) levels was noticed to be elevated in blood lymphocytes of arthritic rats. Exposure of arthritic rats to PEMF at 5 Hzx4 microT x 90 min, produced significant antiexudative effect resulting in the restoration of the altered parameters. The antiinflammatory effect could be partially mediated through the stabilizing action of PEMF on membranes as reflected by the restoration of PMCA and intracellular Ca(2+) levels in blood lymphocytes subsequently inhibiting PGE(2) biosynthesis. The results of this study indicated that PEMF could be developed as a potential therapy for RA in human beings.

BMC Musculoskelet Disord. 2007 Jun 22;8:51.

Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomised placebo-controlled trials.

Bjordal JM, Johnson MI, Lopes-Martins RA, Bogen B, Chow R, Ljunggren AE.

Faculty of Health and Social Sciences, Institute of Physiotherapy, Bergen University College, Moellendalsvn, Bergen Norway. jmb@hib.no

Abstract

BACKGROUND: Treatment efficacy of physical agents in osteoarthritis of the knee (OAK) pain has been largely unknown, and this systematic review was aimed at assessing their short-term efficacies for pain relief.

METHODS: Systematic review with meta-analysis of efficacy within 1-4 weeks and at follow up at 1-12 weeks after the end of treatment.

RESULTS: 36 randomised placebo-controlled trials (RCTs) were identified with 2434 patients where 1391 patients received active treatment. 33 trials satisfied three or more out of five methodological criteria (Jadad scale). The patient sample had a mean age of 65.1 years and mean baseline pain of 62.9 mm on a 100 mm visual analogue scale (VAS). Within 4 weeks of the commencement of treatment manual acupuncture, static magnets and ultrasound therapies did not offer statistically significant short-term pain relief over placebo. Pulsed electromagnetic fields offered a small reduction in pain of 6.9 mm [95% CI: 2.2 to 11.6] (n = 487). Transcutaneous electrical nerve stimulation (TENS, including interferential currents), electro-acupuncture (EA) and low level laser therapy (LLLT) offered clinically relevant pain relieving effects of 18.8 mm [95% CI: 9.6 to 28.1] (n = 414), 21.9 mm [95% CI: 17.3 to 26.5] (n = 73) and 17.7 mm [95% CI: 8.1 to 27.3] (n = 343) on VAS respectively versus placebo control. In a subgroup analysis of trials with assumed optimal doses, short-term efficacy increased to 22.2 mm [95% CI: 18.1 to 26.3] for TENS, and 24.2 mm [95% CI: 17.3 to 31.3] for LLLT on VAS. Follow-up data up to 12 weeks were sparse, but positive effects seemed to persist for at least 4 weeks after the course of LLLT, EA and TENS treatment was stopped.

Pain Res Manag. 2006 Summer;11(2):85-90.

Exposure to a specific pulsed low-frequency magnetic field: a double-blind placebo-controlled study of effects on pain ratings in rheumatoid arthritis and fibromyalgia patients.

Shupak NM, McKay JC, Nielson WR, Rollman GB, Prato FS, Thomas AW.

Lawson Health Research Institute, St. Joseph’s Health Care, London, Ontario N6A 4V2.

Abstract

BACKGROUND: Specific pulsed electromagnetic fields (PEMFs) have been shown to induce analgesia (antinociception) in snails, rodents and healthy human volunteers.

OBJECTIVE: The effect of specific PEMF exposure on pain and anxiety ratings was investigated in two patient populations.

DESIGN: A double-blind, randomized, placebo-controlled parallel design was used.

METHOD: The present study investigated the effects of an acute 30 min magnetic field exposure (less than or equal to 400 microTpk; less than 3 kHz) on pain (McGill Pain Questionnaire [MPQ], visual analogue scale [VAS]) and anxiety (VAS) ratings in female rheumatoid arthritis (RA) (n=13; mean age 52 years) and fibromyalgia (FM) patients (n=18; mean age 51 years) who received either the PEMF or sham exposure treatment.

RESULTS: A repeated measures analysis revealed a significant pre-post-testing by condition interaction for the MPQ Pain Rating Index total for the RA patients, F(1,11)=5.09, P<0.05, estimate of effect size = 0.32, power = 0.54. A significant pre-post-effect for the same variable was present for the FM patients, F(1,15)=16.2, P<0.01, estimate of effect size = 0.52, power =0.96. Similar findings were found for MPQ subcomponents and the VAS (pain). There was no significant reduction in VAS anxiety ratings pre- to post-exposure for either the RA or FM patients.

CONCLUSION: These findings provide some initial support for the use of PEMF exposure in reducing pain in chronic pain populations and warrants continued investigation into the use of PEMF exposure for short-term pain relief.

Z Orthop Ihre Grenzgeb. 2005 Sep-Oct;143(5):544-50.

Adjuvant treatment of knee osteoarthritis with weak pulsing magnetic fields. Results of a placebo-controlled trial prospective clinical trial.

[Article in German]

Fischer G, Pelka RB, Barovic J.

Institut für Hygiene an der Universität Graz, Osterreich.

Abstract

PURPOSE: The aim of this study was the objective control of the therapeutic effect of weak pulsing magnetic fields (series of periodically repeating square pulses increasing according to an e-function, frequencies of 10, 20, 30, and 200-300 Hz) by means of a double-blind study on osteoarthritis of the knee. Measured parameters were the Knee Society score, pain sensation, blood count and cardiocirculatory values.

METHODS: 36 placebo and 35 verum test persons (all with a knee gap smaller than 3 mm) were exposed daily for 16 minutes over 6 weeks to a low frequency magnetic field (flux densities increasing gradually from 3.4 up to 13.6 microT) encompassing the whole body. The last data collection was made 4 weeks after the end of treatment.

RESULTS: Principally, the statistically ensured results exclusively favour the used magnetic field therapy; by far the greatest number of at least significant differences was found at the end of the whole treatment, lasting 6 weeks. In particular, it is striking that all 4 questioned pain scales showed at least significant improvements in favour of the verum collective; also the walking distance was increased. As another confirmed fact, even after 4 weeks without therapy the persistence of several functional and analgesic effects could be documented.

CONCLUSIONS: Predominantly, on the one hand, pain relief in osteoarthritis patients was confirmed by a double-blind trial, on the other hand, increases in mobility could be proven. Furthermore, we describe mainly the modes of action of low frequency magnetic energy and 3 physical concepts that are seen as the connecting link between electromagnetic fields coupled into connective tissue and biochemical repair and growth processes in bones and cartilage. Proceeding from the results of this and preceding studies, one has to consider seriously whether this kind of magnetic field application should not be employed as cost-effective and side effect-free alternative or adjuvant form of therapy in the field of orthopaedic disorders.

Bioelectromagnetics. 2005 Sep;26(6):431-9.

Optimization of pulsed electromagnetic field therapy for management of arthritis in rats.

Kumar VS, Kumar DA, Kalaivani K, Gangadharan AC, Raju KV, Thejomoorthy P, Manohar BM, Puvanakrishnan R.

Department of Pharmacology and Toxicology, Madras Veterinary College, Vepery, Chennai, India.

Studies were undertaken to find out the effects of low frequency pulsed electromagnetic field (PEMF) in adjuvant induced arthritis (AIA) in rats, a widely used model for screening potential therapies for rheumatoid arthritis (RA). AIA was induced by an intradermal injection of a suspension of heat killed Mycobacterium tuberculosis (500 mug/0.1 ml) into the right hind paw of male Wistar rats. This resulted in swelling, loss of body weight, increase in paw volume as well as the activity of lysosomal enzymes viz., acid phosphatase, cathepsin D, and beta-glucuronidase and significant radiological and histological changes. PEMF therapy for arthritis involved optimization of three significant factors, viz., frequency, intensity, and duration; and the waveform used is sinusoidal. The use of factorial design in lieu of conventional method resulted in the development of an ideal combination of these factors. PEMF was applied using a Fransleau-Braunbeck coil system. A magnetic field of 5 Hz x 4 muT x 90 min was found to be optimal in lowering the paw edema volume and decreasing the activity of lysosomal enzymes. Soft tissue swelling was shown to be reduced as evidenced by radiology. Histological studies confirmed reduction in inflammatory cells infiltration, hyperplasia, and hypertrophy of cells lining synovial membrane. PEMF was also shown to have a membrane stabilizing action by significantly inhibiting the rate of release of beta-glucuronidase from lysosomal rich and sub-cellular fractions. The results indicated that PEMF could be developed as a potential therapy in the treatment of arthritis in humans.

Biomed Pharmacother. 2005 Aug 2; [Epub ahead of print]

Effects of pulsed electromagnetic fields on articular hyaline cartilage: review of experimental and clinical studies.

Fini M, Giavaresi G, Carpi A, Nicolini A, Setti S, Giardino R.

Experimental Surgery Department, Research Institute Codivilla-Putti-Rizzoli, Orthopedic Institute, via di Barbiano 1/10, 40136 Bologna, Italy.

Osteoarthritis (OA) is the most common disorder of the musculoskeletal system and is a consequence of mechanical and biological events that destabilize tissue homeostasis in articular joints. Controlling chondrocyte death and apoptosis, function, response to anabolic and catabolic stimuli, matrix synthesis or degradation and inflammation is the most important target of potential chondroprotective treatment, aimed to retard or stabilize the progression of OA. Although many drugs or substances have been recently introduced for the treatment of OA, the majority of them relieve pain and increase function, but do not modify the complex pathological processes that occur in these tissues. Pulsed electromagnetic fields (PEMFs) have a number of well-documented physiological effects on cells and tissues including the upregulation of gene expression of members of the transforming growth factor beta super family, the increase in glycosaminoglycan levels, and an anti-inflammatory action. Therefore, there is a strong rationale supporting the in vivo use of biophysical stimulation with PEMFs for the treatment of OA. In the present paper some recent experimental in vitro and in vivo data on the effect of PEMFs on articular cartilage were reviewed. These data strongly support the clinical use of PEMFs in OA patients.

Osteoarthritis Cartilage. 2005 Jul;13(7):575-81. Treatment of knee osteoarthritis with pulsed electromagnetic fields: a randomized, double-blind, placebo-controlled study. Thamsborg G, Florescu A, Oturai P, Fallentin E, Tritsaris K, Dissing S. Department of Geriatri and Rheumatology, Glostrup Hospital, 2600 Glostrup, Denmark. OBJECTIVE: The investigation aimed at determining the effectiveness of pulsed electromagnetic fields (PEMF) in the treatment of osteoarthritis (OA) of the knee by conducting a randomized, double-blind, placebo-controlled clinical trial. DESIGN: The trial consisted of 2h daily treatment 5 days per week for 6 weeks in 83 patients with knee OA. Patient evaluations were done at baseline and after 2 and 6 weeks of treatment. A follow-up evaluation was done 6 weeks after treatment. Activities of daily living (ADL), pain and stiffness were evaluated using the Western Ontario and McMaster Universities (WOMAC) questionnaire. RESULTS: Within group analysis revealed a significant improvement in ADL, stiffness and pain in the PEMF-treated group at all evaluations. In the control group there was no effect on ADL after 2 weeks and a weak significance was seen after 6 and 12 weeks. Significant effects were seen on pain at all evaluations and on stiffness after 6 and 12 weeks. Between group analysis did not reveal significant improvements over time. Analysis of ADL score for the PEMF-treated group revealed a significant correlation between less improvement and increasing age. Analysis of patients <65 years using between group analysis revealed a significant improvement for stiffness on treated knee after 2 weeks, but this effect was not observed for ADL and pain. CONCLUSIONS: Applying between group analysis we were unable to demonstrate a beneficial symptomatic effect of PEMF in the treatment of knee OA in all patients. However, in patients <65 years of age there is significant and beneficial effect of treatment related to stiffness Orthop Res. 2005 Jul;23(4):899-908. Epub 2005 Mar 17. Pulsed electromagnetic fields reduce knee osteoarthritis lesion progression in the aged Dunkin Hartley guinea pig. Fini M, Giavaresi G, Torricelli P, Cavani F, Setti S, Cane V, Giardino R. Department of Experimental Surgery, Codivilla-Putti Research Institute, Rizzoli Institute of Orthopaedics, Via di Barbiano, 1/10, 40136 Bologna, Italy. milena.fini@ior.it An experimental in vivo study was performed to test if the effect of Pulsed Electromagnetic Fields (PEMFs) on chondrocyte metabolism and adenosine A2a agonist activity could have a chondroprotective effect on the knee of Dunkin Hartley guinea-pigs of 12 months with spontaneously developed osteoarthritis (OA). After a pilot study, 10 animals were randomly divided into two groups: PEMF-treated group (6 h/day for 3 months) and Sham-treated group. Microradiography and histomorphometry were performed on the entire articular surface of knee joints used in evaluating chondropathy severity, cartilage thickness (CT), cartilage surface Fibrillation Index (FI), subchondral bone plate thickness (SBT) and histomorphometric characteristics of trabecular epiphyseal bone. The PEMF-treated animals showed a significant reduction of chondropathy progression in all knee examined areas (p<0.05). CT was significantly higher (p<0.001) in the medial tibia plateaus of the PEMF-treated group when compared to the Sham-treated group. The highest value of FI was observed in the medial tibia plateau of the Sham-treated group (p<0.05). Significant lower values were observed in SBT of PEMF-treated group in comparison to Sham-treated group in all knee examined areas (p<0.05). The present study results show that PEMFs preserve the morphology of articular cartilage and slower the progression of OA lesions in the knee of aged osteoarthritic guinea pigs. The chondroprotective effect of PEMFs was demonstrated not only in the medial tibial plateau but also on the entire articular surface of the knee. B Rheumatol Int. 2005 Jun 29; [Epub ahead of print] The effect of pulsed electromagnetic fields in the treatment of cervical osteoarthritis: a randomized, double-blind, sham-controlled trial. Sutbeyaz ST, Sezer N, Koseoglu BF. Ankara Physical Medicine and Rehabilitation Education and Research Hospital, Turk ocagi S No: 3 Sihhiye, Ankara, Turkey. The purpose of this study was to evaluate the effect of electromagnetic field therapy (PEMF) on pain, range of motion (ROM) and functional status in patients with cervical osteoarthritis (COA). Thirty-four patients with COA were included in a randomized, double-blind study. PEMF was administrated to the whole body using a mat 1.8×0.6 m in size. During the treatment, the patients lay on the mat for 30 min per session, twice a day for 3 weeks. Pain levels in the PEMF group decreased significantly after therapy (p<0.001), but no change was observed in the placebo group. The active ROM, paravertebral muscle spasm and neck pain and disability scale (NPDS) scores improved significantly after PEMF therapy (p<0.001) but no change was observed in the sham group. The results of this study are promising, in that PEMF treatment may offer a potential therapeutic adjunct to current COA therapies in the future.

Osteoarthritis Cartilage. 2003 Jun;11(6):455-62.

Modification of osteoarthritis by pulsed electromagnetic field–a morphological study.

Ciombor DM, Aaron RK, Wang S, Simon B.

Department of Orthopaedics, Brown Medical School, Providence, RI 02906, USA.

Abstract

OBJECTIVE: Hartley guinea pigs spontaneously develop arthritis that bears morphological, biochemical, and immunohistochemical similarities to human osteoarthritis. It is characterized by the appearance of superficial fibrillation by 12 months of age and severe cartilage lesions and eburnation by 18 months of age. This study examines the effect of treatment with a pulsed electromagnetic field (PEMF) upon the morphological progression of osteoarthritis in this animal model.

DESIGN: Hartley guinea pigs were exposed to a specific PEMF for 1h/day for 6 months, beginning at 12 months of age. Control animals were treated identically, but without PEMF exposure. Tibial articular cartilage was examined with histological/histochemical grading of the severity of arthritis, by immunohistochemistry for cartilage neoepitopes, 3B3(-) and BC-13, reflecting enzymatic cleavage of aggrecan, and by immunoreactivity to collagenase (MMP-13) and stromelysin (MMP-3). Immunoreactivity to TGFbeta, interleukin (IL)-1beta, and IL receptor antagonist protein (IRAP) antibodies was examined to suggest possible mechanisms of PEMF activity.

RESULTS: PEMF treatment preserves the morphology of articular cartilage and retards the development of osteoarthritic lesions. This observation is supported by a reduction in the cartilage neoepitopes, 3B3(-) and BC-13, and suppression of the matrix-degrading enzymes, collagenase and stromelysin. Cells immunopositive to IL-1 are decreased in number, while IRAP-positive cells are increased in response to treatment. PEMF treatment markedly increases the number of cells immunopositive to TGFbeta.

CONCLUSIONS: Treatment with PEMF appears to be disease-modifying in this model of osteoarthritis. Since TGFbeta is believed to upregulate gene expression for aggrecan, downregulate matrix metalloprotease and IL-1 activity, and upregulate inhibitors of matrix metalloprotease, the stimulation of TGFbeta may be a mechanism through which PEMF favorably affects cartilage homeostasis.

The Effect of Pulsed Electromagnetic Fields in the Treatment of Osteoarthritis of the Knee and Cervical Spine.  Report of Randomized, Double-Blind, Placebo Controlled Trials

Trock D. et.al. Department of Medicine, Danbury Hospital, CT. J. of Rheumatology

OBJECTIVE. We conducted a randomized, double blind clinical trial to determine the effectiveness of pulsed electromagnetic fields (PEMF) in the treatment of osteoarthritis (OA) of the knee and cervical spine.

METHODS. A controlled trial of 18 half-hour active or placebo treatments was conducted in 86 patients with OA of the knee and 81 patients with OA of the cervical spine, in which pain was evaluated using a 10 cm visual analog scale, activities of daily living using a series of questions (answered by the patient as never, sometimes, most of the time, or always), pain on passive motion (recorded as none, slight, moderate, or severe), and joint tenderness (recorded using a modified Ritchie scale). Global evaluations of improvement were made by the patient and examining physician. Evaluations were made at baseline, midway, end of treatment, and one month after completion of treatment.

RESULTS. Matched pair t tests showed extremely significant changes from baseline for the treated patients in both knee and cervical spine studies at the end of treatment and the one month follow-up observations, whereas the changes in the placebo patients showed lesser degrees of significance at the end of treatment, and had lost significance for most variables at the one month follow-up. Means of the treated group of patients with OA of the knee showed greater improvement from baseline values than the placebo group by the end of treatment and at the one month follow-up observation. Using the 2-tailed t test, at the end of treatment the differences in the means of the 2 groups reached statistical significance for pain, pain on motion, and both the patient overall assessment and the physician global assessment. The means of the treated patients with OA of the cervical spine showed greater improvement from baseline than the placebo group for most variables at the end of treatment and one month follow-up observations; these differences reached statistical significance at one or more observation points for pain, pain on motion, and tenderness.

CONCLUSION. PEMF has therapeutic benefit in painful OA of the knee or cervical spine.

J Med Eng Technol. 2002 Nov-Dec;26(6):253-8.

Comparison between the analgesic and therapeutic effects of musically modulated electromagnetic field (TAMMEF) and those if a 100 Hz electromagnetic field: blind experiemnt on patients suffering from cervical spondylosis or shoulder periarthritis.

Rigato M, Battisti E, Fortunato M, Giordano N.

Department of Physics, Section of Medical Physics University of Sienna, Italy. rigato@unisi.it

The analgesic-therapeutic efficacy and tolerability of a low-frequency electromagnetic field (ELF), modulated at a frequency of 100 Hz with a sinusoidal waveform and mean induction of a few gauss, has been demonstrated by the authors in numerous previous studies of various hyperalgic pathologies, particularly of the locomotor apparatus. In the present study, the authors tested a new type of all-inclusive field, denoted TAMMEF, whose parameters (frequency, intensity, waveform) are modified in time, randomly varying within the respective ranges, so that all the possible codes can occur during a single application. For the comparison, 150 subjects (118 women and 32 men, between 37 and 66 years of age) were enrolled. They were affected by cervical spondylosis (101 cases) or shoulder periarthritis (49 cases). Unbeknownst to them, they were randomly divided into three groups of 50 subjects. One group was exposed to the new TAMMEF, another group to the usual ELF, and the third group to simulated treatment. The results show that the effects of the new TAMMEF therapy are equivalent to those obtained with the ELF.

: Curr Opin Rheumatol. 2002 Sep;14(5):603-7.

Nonpharmacologic management of osteoarthritis.

Sharma L.

Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA. L-Sharma@northwestern.edu

Several nonpharmacologic interventions for osteoarthritis are in different stages of development, investigation, and application. Such interventions capitalize on current knowledge of the causes of symptoms, disease progression, and disability in patients with osteoarthritis. Many nonpharmacologic interventions are low in cost and incorporate self-management approaches or home-based activities and, as such, may ultimately have substantial public health impact. Recent studies and reviews of exercise, weight loss, education, inserts, footwear, bracing, therapeutic ultrasound, acupuncture, and pulsed electromagnetic field therapy will be highlighted in this review. For many of these interventions, further investigation will be necessary to define their place in the management of osteoarthritis.

Wien Klin Wochenschr. 2002 Aug 30;114(15-16):678-84.

Pulsed magnetic field therapy for osteoarthritis of the knee–a double-blind sham-controlled trial.

Nicolakis P, Kollmitzer J, Crevenna R, Bittner C, Erdogmus CB, Nicolakis J.

Department of Physical Medicine and Rehabilitation, AKH Wien, University of Vienna, Vienna, Austria. Peter.nicolakis@akh-wien.ac.at

BACKGROUND AND METHODS: Pulsed magnetic field therapy is frequently used to treat the symptoms of osteoarthritis, although its efficacy has not been proven. We conducted a randomized, double-blind comparison of pulsed magnetic field and sham therapy in patients with symptomatic osteoarthritis of the knee. Patients were assigned to receive 84 sessions, each with a duration of 30 minutes, of either pulsed magnetic field or sham treatment. Patients administered the treatment on their own at home, twice a day for six weeks.

RESULTS: According to a sample size estimation, 36 consecutive patients were enrolled. 34 patients completed the study, two of whom had to be excluded from the statistical analysis, as they had not applied the PMF sufficiently. Thus, 15 verum and 17 sham-treated patients were enrolled in the statistical analysis. After six weeks of treatment the WOMAC Osteoarthritis Index was reduced in the pulsed magnetic field-group from 84.1 (+/- 45.1) to 49.7 (+/- 31.6), and from 73.7 (+/- 43.3) to 66.9 (+/- 52.9) in the sham-treated group (p = 0.03). The following secondary parameters improved in the pulsed magnetic field group more than they did in the sham group: gait speed at fast walking [+6.0 meters per minute (1.6 to 10.4) vs. -3.2 (-8.5 to 2.2)], stride length at fast walking [+6.9 cm (0.2 to 13.7) vs. -2.9 (-8.8 to 2.9)], and acceleration time in the isokinetic dynamometry strength tests [-7.0% (-15.2 to 1.3) vs. 10.1% (-0.3 to 20.6)].

CONCLUSION: In patients with symptomatic osteoarthritis of the knee, PMF treatment can reduce impairment in activities of daily life and improve knee function.

Cochrane Database Syst Rev. 2002;(1):CD003523.

Electromagnetic fields for the treatment of osteoarthritis.

Hulme J, Robinson V, DeBie R, Wells G, Judd M, Tugwell P.

Cochrane Collaborating Center, Center for Global Health, Institute of Population Health – University of Ottawa, 1 Stewart Street, Ottawa, Ontario, Canada, K1N 6N5. jhulme@uottawa.ca

BACKGROUND: As the focus for osteoarthritis (OA) treatment shifts away from drug therapy, we consider the effectiveness of pulsed electric stimulation which is proven to stimulate cartilage growth on the cellular level.

OBJECTIVES: 1)To assess the effectiveness of pulsed electric stimulation for the treatment of osteoarthritis (OA). 2) To assess the most effective and efficient method of applying an electromagnetic field, through pulsed electromagnetic fields (PEMF) or electric stimulation, as well as the consideration of length of treatment, dosage, and the frequency of the applications.

SEARCH STRATEGY: We searched PREMEDLINE, MEDLINE, HealthSTAR, CINAHL, PEDro, and the Cochrane Controlled Trials Register (CCTR) up to and including 2001. This included searches through the coordinating offices of the trials registries of the Cochrane Field of Physical and Related Therapies and the Cochrane Musculoskeletal Group for further published and unpublished articles. The electronic search was complemented by hand searches and experts in the area.

SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials that compared PEMF or direct electric stimulation against placebo in patients with OA.

DATA COLLECTION AND ANALYSIS: Two reviewers determined the studies to be included in the review based on inclusion and exclusion criteria (JH,VR) and extracted the data using pre-developed extraction forms for the Cochrane Musculoskeletal Group. The methodological quality of the trials was assessed by the same reviewers using a validated scale (Jadad 1996). Osteoarthritis outcome measures were extracted from the publications according to OMERACT guidelines (Bellamy 1997) and additional secondary outcomes considered.

MAIN RESULTS: Only three studies with a total of 259 OA patients were included in the review. Electrical stimulation therapy had a small to moderate effect on outcomes for knee OA, all statistically significant with clinical benefit ranging from 13-23% greater with active treatment than with placebo. Only 2 outcomes for cervical OA were significantly different with PEMF treatment and no clinical benefit can be reported with changes of 12% or less.

REVIEWER’S CONCLUSIONS: Current evidence suggests that electrical stimulation therapy may provide significant improvements for knee OA, but further studies are required to confirm whether the statistically significant results shown in these trials confer to important benefits.

Arch Phys Med Rehabil. 2001 Oct;82(10):1453-60.

Two configurations of static magnetic fields for treating rheumatoid arthritis of the knee: a double-blind clinical trial.

Segal NA, Toda Y, Huston J, Saeki Y, Shimizu M, Fuchs H, Shimaoka Y, Holcomb R, McLean MJ.

Vanderbilt University Medical School, Nashville, TN 37232, USA.

Abstract

OBJECTIVE: To assess the efficacy of a nonpharmacologic, noninvasive static magnetic device as adjunctive therapy for knee pain in patients with rheumatoid arthritis (RA).

DESIGN: Randomized, double-blind, controlled, multisite clinical trial.

SETTING: An American and a Japanese academic medical center as well as 4 community rheumatology and orthopedics practices.

PATIENTS: Cohort of 64 patients over age 18 years with rheumatoid arthritis and persistent knee pain, rated greater than 40/100mm, despite appropriate use of medications.

INTERVENTION: Four blinded MagnaBloc (with 4 steep field gradients) or control devices (with 1 steep field gradient) were taped to a knee of each subject for 1 week.

MAIN OUTCOME MEASURES: The American College of Rheumatology recommended core set of disease activity measures for RA clinical trials and subjects’ assessment of treatment outcome.

RESULTS: Subjects randomly assigned to the MagnaBloc (n = 38) and control treatment groups (n = 26) reported baseline pain levels of 63/100mm and 61/100mm, respectively. A greater reduction in reported pain in the MagnaBloc group was sustained through the 1-week follow-up (40.4% vs 25.9%) and corroborated by twice daily pain diary results (p < .0001 for each vs baseline). However, comparison between the 2 groups demonstrated a statistically insignificant difference (p < .23). Subjects in the MagnaBloc group reported an average decrease in their global assessment of disease activity of 33% over 1 week, as compared with a 2% decline in the control group (p < .01). After 1 week, 68% of the MagnaBloc treatment group reported feeling better or much better, compared with 27% of the control group, and 29% and 65%, respectively, reported feeling the same as before treatment (p < .01).

CONCLUSIONS: Both devices demonstrated statistically significant pain reduction in comparison to baseline, with concordance across multiple indices. However, a significant difference was not observed between the 2 treatment groups (p < .23). In future studies, the MagnaBloc treatment should be compared with a nonmagnetic placebo treatment to characterize further its therapeutic potential for treating RA. This study did elucidate methods for conducting clinical trials with magnetic devices.

Curr Med Res Opin. 2001;17(3):190-6.

Magnetic pulse treatment for knee osteoarthritis: a randomised, double-blind, placebo-controlled study.

Pipitone N, Scott DL.

Rheumatology Department, King’s College Hospital (Dulwich), London, UK.

Abstract

We assessed the efficacy and tolerability of low-frequency pulsed electromagnetic fields (PEMF) therapy in patients with clinically symptomatic knee osteoarthritis (OA) in a randomised, placebo-controlled, double-blind study of six weeks’ duration. Patients with radiographic evidence and symptoms of OA (incompletely relieved by conventional treatments), according to the criteria of the American College of Rheumatology, were recruited from a single tertiary referral centre. 75 patients fulfilling the above criteria were randomised to receive active PEMF treatment by unipolar magnetic devices (Medicur) manufactured by Snowden Healthcare (Nottingham, UK) or placebo. Six patients failed to attend after the screening and were excluded from analysis. The primary outcome measure was reduction in overall pain assessed on a four-point Likert scale ranging from nil to severe. Secondary outcome measures included the WOMAC Osteoarthritis Index (Likert scale) and the EuroQol (Euro-Quality of Life, EQ-5D). Baseline assessments showed that the treatment groups were equally matched. Although there were no significant differences between active and sham treatment groups in respect of any outcome measure after treatment, paired analysis of the follow-up observations on each patient showed significant improvements in the actively treated group in the WOMAC global score (p = 0.018), WOMAC pain score (p = 0.065), WOMAC disability score (p = 0.019) and EuroQol score (p = 0.001) at study end compared to baseline. In contrast, there were no improvements in any variable in the placebo-treated group. There were no clinically relevant adverse effects attributable to active treatment. These results suggest that the Medicur unipolar magnetic devices are beneficial in reducing pain and disability in patients with knee OA resistant to conventional treatment in the absence of significant side-effects. Further studies using different types of magnetic devices, treatment protocols and patient populations are warranted to confirm the general efficacy of PEMF therapy in OA and other conditions.

Altern Ther Health Med. 2001 Sep-Oct;7(5):54-64, 66-9.

Low-amplitude, extremely low frequency magnetic field for the treatment of osteoarthritic knees: a double-blind clinical study.

Jacobson JI, Gorman R, Yamanashi WS, Saxena BB, Clayton L.

Institute of Theoretical Physics and Advanced Studies for Biophysical Research, Perspectivism Foundation, 2006 Mainsail Cir, Jupiter, FL 33477-1418, USA. drjjacobson@aol.com

CONTEXT: Noninvasive magnetotherapeutic approaches to bone healing have been successful in past clinical studies. OBJECTIVE: To determine the effectiveness of low-amplitude, extremely low frequency magnetic fields on patients with knee pain due to osteoarthritis. DESIGN: Placebo-controlled, randomized, double-blind clinical study.

SETTING: 4 outpatient clinics.

PARTICIPANTS: 176 patients were randomly assigned to 1 of 2 groups, the placebo group (magnet off) or the active group (magnet on).

INTERVENTION: 6-minute exposure to each magnetic field signal using 8 exposure sessions for each treatment session, the number of treatment sessions totaling 8 during a 2-week period, yielded patients being exposed to uniform magnetic fields for 48 minutes per treatment session 8 times in 2 weeks. The magnetic fields used in this study were generated by a Jacobson Resonator, which consists of two 18-inch diameter (46-cm diameter) coils connected in series, in turn connected to a function generator via an attenuator to obtain the specific amplitude and frequency. The range of magnetic field amplitudes used was from 2.74 x 10(-7) to 3.4 x 10(-8) G, with corresponding frequencies of 7.7 to 0.976 Hz.

OUTCOME MEASURES: Each subject rated his or her pain level from 1 (minimal) to 10 (maximal) before and after each treatment and 2 weeks after treatment. Subjects also recorded their pain intensity in a diary while outside the treatment environment for 2 weeks after the last treatment session (session 8) twice daily: upon awakening (within 15 minutes) and upon retiring (just before going to bed at night).

RESULTS: Reduction in pain after a treatment session was significantly (P < .001) greater in the magnet-on group (46%) compared to the magnet-off group (8%).

CONCLUSION: Low-amplitude, extremely low frequency magnetic fields are safe and effective for treating patients with chronic knee pain due to osteoarthritis.

Acta Med Austriaca. 2000;27(3):61-8.

Clinical effectiveness of magnetic field therapy–a review of the literature

[Article in German].

Quittan M, Schuhfried O, Wiesinger GF, Fialka-Moser V.

Universitätsklinik für Physikalische Medizin und Rehabilitation, Wien. michael.quittan@akh-wien.ac.at

Abstract

To verify the efficacy of electromagnetic fields on various diseases we conducted a computer-assisted search of the pertinent literature. The search was performed with the aid of the Medline and Embase database (1966-1998) and reference lists. Clinical trials with at least one control group were selected. The selection criteria were met by 31 clinical studies. 20 trials were designed double-blind, randomised and placebo-controlled. The studies were categorised by indications. Electromagnetic fields were applied to promote bone-healing, to treat osteoarthritis and inflammatory diseases of the musculoskeletal system, to alleviate pain, to enhance healing of ulcers and to reduce spasticity. The action on bone healing and pain alleviation of electromagnetic fields was confirmed in most of the trials. In the treatment of other disorders the results are contradictory. Application times varied between 15 minutes and 24 hours per day for three weeks up to eighteen months. There seems to be a relationship between longer daily application time and positive effects particular in bone-healing. Patients were treated with electromagnetic fields of 2 to 100 G (0.2 mT to 10 mT) with a frequency between 12 and 100 Hz. Optimal dosimetry for therapy with electromagnetic fields is yet not established.

Rheum Dis Clin North Am. 2000 Feb;26(1):51-62, viii.

Electromagnetic fields and magnets. Investigational treatment for musculoskeletal disorders.

Trock DH.

Yale University School of Medicine, New Haven, Connecticut, USA.

Abstract

Certain pulsed electromagnetic fields (PEMF) affect the growth of bone and cartilage in vitro, with potential application as an arthritis treatment. PEMF stimulation is already a proven remedy for delayed fractures, with potential clinical application for osteoarthritis, osteonecrosis of bone, osteoporosis, and wound healing. Static magnets may provide temporary pain relief under certain circumstances. In both cases, the available data is limited. The mechanisms underlying the use of PEMF and magnets are discussed.

Vopr Kurortol Fizioter Lech Fiz Kult. 1997 Sep-Oct;(5):25-6. Experience in using saprogel mud in combination with a magnetic field in treating cervical osteochondrosis. [Article in Russian] Samutin NM. Patients with cervical osteochondrosis were successfully treated with Deshembinskoe Lake [correction of Deshembinskaya] sapropel mud in combination with exposure to magnetic field. The details of this treatment regimen are described. Combination of pelotherapy with effects of the magnetic field proved beneficial for patients with cervical osteochondrosis. J Rheumatol. 1993 Mar;20(3):456-60. A double-blind trial of the clinical effects of pulsed electromagnetic fields in osteoarthritis. Trock DH, Bollet AJ, Dyer RH Jr, Fielding LP, Miner WK, Markoll R. Department of Medicine (Rheumatology), Danbury Hospital, CT 06810. Abstract OBJECTIVE: Further evaluation of pulsed electromagnetic fields (PEMF), which have been observed to produce numerous biological effects, and have been used to treat delayed union fractures for over a decade. METHODS: In a pilot, double-blind randomized trial, 27 patients with osteoarthritis (OA), primarily of the knee, were treated with PEMF. Treatment consisted of 18 half-hour periods of exposure over about 1 month in a specially designed noncontact, air-coil device. Observations were made on 6 clinical variables at baseline, midpoint of therapy, end of treatment and one month later; 25 patients completed treatment. RESULTS: An average improvement of 23-61% occurred in the clinical variables observed with active treatment, while 2 to 18% improvement was observed in these variables in placebo treated control patients. No toxicity was observed. CONCLUSION: The decreased pain and improved functional performance of treated patients suggests that this configuration of PEMF has potential as an effective method of improving symptoms in patients with OA. This method warrants further clinical investigation. Scand J Rehabil Med. 1992;24(1):51-9. Low energy high frequency pulsed electromagnetic therapy for acute whiplash injuries.  A double blind randomized controlled study. Foley-Nolan D. et.al. Mater Hospital, Dublin, Ireland. The standard treatment of acute whiplash injuries (soft collar and analgesia) is frequently unsuccessful. Pulsed electromagnetic therapy PEMT has been shown to have pro-healing and anti-inflammatory effects. This study examines the effect of PEMT on the acute whiplash syndrome. PEMT as described is safe for domiciliary use and this study suggests that PEMT has a beneficial effect in the management of the acute whiplash injury. Minerva Anestesiol. 1989 Jul-Aug;55(7-8):295-9. Pulsed magnetic fields.  Observations in 353 patients suffering from chronic pain. [Article in Italian] Di Massa A, Misuriello I, Olivieri MC, Rigato M. Three hundred-fifty-three patients with chronic pain have been treated with pulsed electromagnetic fields. In this work the Authors show the result obtained in the unsteady follow-up (2-60 months). The eventual progressive reduction of benefits is valued by Spearman’s test. We noted the better results in the group of patients with post-herpetic pain (deafferentation) and in patients simultaneously suffering from neck and low back pain.
Lik Sprava. 1997 Sep-Oct;(5):170-2.

A comparative evaluation of the efficacy of magneto- and laser therapy in patients with osteoarthrosis deformans.

[Article in Russian]

Selivonenko VG, Syvolap VD, Porada LV, Medvedeva VN, Boev SS, Morozov AI, Slin’ko VG, Berest SM, Garbuz LN, Sholokh SG.

A comparative evaluation of efficacy of magneto- and laser therapy was carried out in 82 patients with osteoarthrosis deformans. The magnetic field and laser irradiation dispelled the pain syndrome and synovitis manifestations. It is recommendable that the multiple-modality therapy of patients with osteoarthrosis deformans should involve magneto- and laser therapy (15 to 20 procedures per one course) that improve results of the treatment being received and allow the time of hospitalization to be reduced at an average by 5 bed-days. Laser appeared to be a very effective mode of treatment. No unfavourable side effects were recordable.

Panminerva Med. 1992 Oct-Dec;34(4):187-96.

Therapeutic effects of pulsed magnetic fields on joint diseases.

Riva Sanseverino E, Vannini A, Castellacci P.

Universita di Bologna, Italy.

The present paper describes the effects of pulsed magnetic fields (MF) on diseases of different joints, in chronic as well as acute conditions where the presence of a phlogistic process is the rule. Optimal parameters for MF applications were sought at the beginning of the study and then applied for 11 years; a technical modification in the MF generator was introduced 5 years ago to satisfy the requirement of a hypothesis advanced to understand the mechanism of MF treatment. 3,014 patients were treated by means of MF at extremely low frequencies and intensities. Patient follow-up was pursued as constantly as possible. Pain removal, recovery of joint mobility and maintenance of the improved conditions represented the parameters for judging the results as good or poor. The chi-square test was applied in order to evaluate the probability that the results are not casual. A general average value of 78.8% of good results and 21.2% of poor results was obtained. Higher (82%) percentages of good results were observed when single joint diseases were considered with respect to multiple joint diseases (polyarthrosis); in the latter, the percentage of good results was definitely lower (66%). The high percentage of good results obtained and the absolute absence of both negative results and undesired side-effects, together with the therapeutic advantage due to a technical modification in the MF generator, led to the conclusion that magnetic field treatment is an excellent physical therapy in cases of joint diseases. A hypothesis is advanced that external magnetic fields influence transmembrane ionic activity.

Arch Phys Med Rehabil. 1991 Apr;72(5):284-7.

Electromagnetic treatment of shoulder periarthritis: a randomized controlled trial of the efficiency and tolerance of magnetotherapy.

Leclaire R, Bourgouin J.

Rehabilitation Medicine Service, Notre Dame Hospital, Montreal, Quebec, Canada.

The potential benefit of magnetotherapy was investigated in 47 consecutive outpatients with periarthritis of the shoulder. Using a controlled triple-blind study design, one group of patients received hot pack applications and passive manual stretching and pulley exercises; the other group received the same therapy plus magnetotherapy. Treatment was administered three times a week. For a maximum of three months, a standardized treatment protocol was used. There was no significant improvement in pain reduction or in range of motion with electromagnetic field therapy. After 12 weeks of therapy, the patients who received magnetotherapy showed mean pain scores of 1.5 (+/- .61 SD) at rest, 2.2 (+/- .76 SD) on movement, and 1.9 (+/- .94 SD), on lying, compared to scores for the control group of 1.4 (+/- .65 SD), 2.2 (+/- .7 SD), and 1.9 (+/- .95 SD), respectively. Linear pain scale scores improved from 71 to 21 for both groups. At 12 weeks the gain in range of motion was mean 109 degrees +/- 46.8 in patients receiving electromagnetic field therapy, compared to 122 degrees +/- 33.4 for the controls (not significant). At entry, the functional handicap score was 53.5 for both groups. At 12 weeks, it was 24 for the magnetotherapy group and 17 for the control group (difference not significant). In conclusion, this study showed no benefit from magnetotherapy in the pain score, range of motion, or improvement of functional status in patients with periarthritis of the shoulder.

Bratisl Lek Listy. 1999 Dec;100(12):678-81.

Personal experience in the use of magnetotherapy in diseases of the musculoskeletal system.

[Article in Slovak]

Sadlonova J, Korpas J.

Ist Dpt of Internal Medicine, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia. bll@fmed.uniba.sk

Therapeutic application of pulsatile electromagnetic field in disorders of motility is recently becoming more frequent. Despite this fact information about the effectiveness of this therapy in the literature are rare. The aim of this study was therefore the treatment of 576 patients who suffered from vertebral syndrome, gonarthritis and coxarthritis. For application of pulsatile electromagnetic field MTU 500H Therapy System was used. Pulsatile electromagnetic field had a frequency valve of 4.5 mT in all studied groups and magnetic induction valve 12.5-18.75 mT in the 1st group. In the 2nd group the intensity was 5.8-7.3 mT and in the 3rd group it was 7.6-11.4 mT. The time of inclination/declination in the 1st group was 20/60 ms, in the 2nd group 40/80 ms and in the 3rd group 40/90 ms. The electromagnetic field was applied during 10 days. In the 1st-3rd day during 20 minutes and in the 4th-10th day during 30 minutes. The therapy was repeated in every patient after 3 months with values of intensity higher by 50%. In the time of pulsatile electro-magnetotherapy the patients were without pharmacotherapy or other physiotherapy. The application of pulsatile electromagnetic field is a very effective therapy of vertebral syndrome, gonarthritis and coxarthritis. The results have shown that the therapy was more effective in patients suffering from gonarthrosis, than in patients with vertebral syndrome and least effective in patients with coxarthosis. Owing to regression of oedema and pain relieve the motility of patients improved. (Tab. 3, Ref. 19.)

Aquired Immune Deficiency Syndrome (AIDS)

Recent Pat Antiinfect Drug Discov. 2012 Feb 17. [Epub ahead of print]

Safety and Efficacy of Setarud (IMOD(TM)) Among People Living with HIV/AIDS: A Review.

Paydary K, Emamzadeh-Fard S, Khorshid HR, Kamali K, Seyed Alinaghi S, Mohraz M.

Source

IRCHA, Imam Khomeini Hospital, Keshavarz Blvd., Tehran, Iran. s_a_alinaghi@yahoo.com

Abstract

The broad use of highly active anti-retroviral therapy (HAART), especially in developing world, has been associated with several problems such as
lactic acidosis, lipodistrophy, pancreatitis, hyperlipidemia, insulin resistance and hepatotoxicity. Extensive use of HAART has also resulted
in emergence of resistant HIV variants. Thereby, a pressing need for development of novel and cost-effective agents arises from these
limitations. Setarud (IMOD(TM)) is a safe, naturally-derived immunomodulator that was introduced for treatment of HIV patients in
Iran. It is prepared as a mixture of herbal extracts including Tanacetum vulgare (tansy), Rosa canina and Urtica dioica (nettle) in addition to
selenium, flavonoids and carotenes. Tanacetum vulgare may relieve anti-inflammatory symptoms and Rosa canina defers blood glucose and
cholesterol elevation. Extracts from Urtica dioica may prevent maturation of myeloid dendritic cells and reduce T cell responses. A
significant rise of CD4 count was observed in HIV patients treated by IMOD(TM) in clinical trial phases, which could be explained by its
immunomodulatory effects. Anti-oxidative activity of compounds in IMOD(TM) might play a role in the clinical outcomes of patients treated
with this drug. Moreover, IMOD(TM) may show improving activity upon lipid profile and liver metabolism. According to studies on IMOD(TM), it
seems that IMOD(TM) has minor side effects. IMOD(TM) with international publication number WO 2007/087825 A1 is an herbal extract which
includes Rosa canina, Urtica dioica, Tanacetum vulgare, and selenium comprising a treatment by pulsed electromagnetic field of high frequency
and is useful in treatment of HIV infection and AIDS. Int J Nanomedicine. 2010 Apr 7;5:157-66.

Magnetic nanoformulation of azidothymidine 5′-triphosphate for targeted delivery across the blood-brain barrier.

Saiyed ZM, Gandhi NH, Nair MP.

Source

Department of Immunology, College of Medicine, Florida International University, Miami, FL, USA.

Abstract

Despite significant advances in highly active antiretroviral therapy (HAART), the prevalence of neuroAIDS remains high. This is mainly attributed to inability of antiretroviral therapy (ART) to cross the blood-brain barrier (BBB), thus resulting in insufficient drug concentration within the brain. Therefore, development of an active drug targeting system is an attractive strategy to increase the efficacy and delivery of ART to the brain. We report herein development of magnetic azidothymidine 5′-triphosphate (AZTTP) liposomal nanoformulation and its ability to transmigrate across an in vitro BBB model by application of an external magnetic field. We hypothesize that this magnetically guided nanoformulation can transverse the BBB by direct transport or via monocyte-mediated transport. Magnetic AZTTP liposomes were prepared using a mixture of phosphatidyl choline and cholesterol. The average size of prepared liposomes was about 150 nm with maximum drug and magnetite loading efficiency of 54.5% and 45.3%, respectively. Further, magnetic AZTTP liposomes were checked for transmigration across an in vitro BBB model using direct or monocyte-mediated transport by application of an external magnetic field. The results show that apparent permeability of magnetic AZTTP liposomes was 3-fold higher than free AZTTP. Also, the magnetic AZTTP liposomes were efficiently taken up by monocytes and these magnetic monocytes showed enhanced transendothelial migration compared to normal/non-magnetic monocytes in presence of an external magnetic field. Thus, we anticipate that the developed magnetic nanoformulation can be used for targeting active nucleotide analog reverse transcriptase inhibitors to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat neuroAIDS. J Neurovirol. 2009 Jul;15(4):343-7.

AZT 5′-triphosphate nanoformulation suppresses human immunodeficiency virus type 1 replication in peripheral blood mononuclear cells.

Saiyed ZM, Gandhi NH, Nair MP.

Source

Department of Immunology, College of Medicine, Florida International University, Miami, Florida 33199, USA.

Abstract

Inefficient cellular phosphorylation of nucleoside and nucleotide analog reverse transcriptase inhibitors (NRTIs) to their active nucleoside 5′-triphosphate (NTPs) form is one of the limitations for human immunodeficiency virus (HIV) therapy. We report herein direct binding of 3′-azido-3′-deoxythymidine-5′-triphosphate (AZTTP) onto magnetic nanoparticles (Fe(3)O(4); magnetite) due to ionic interaction. This magnetic nanoparticle bound AZTTP (MP-AZTTP) completely retained its biological activity as assessed by suppression of HIV-1 replication in peripheral blood mononuclear cells. The developed MP-AZTTP nanoformulation can be used for targeting active NRTIs to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat NeuroAIDs.

Int J Pharm. 2008 Mar 3;351(1-2):271-81. Epub 2007 Sep 22.

Electromagnetic interference in the permeability of saquinavir across the blood-brain barrier using nanoparticulate carriers.

Kuo YC, Kuo CY.

Source

Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan 62102, Republic of China. chmyck@ccu.edu.tw

Abstract

Transport of antiretroviral agents across the blood-brain barrier (BBB) is of key importance to the treatment for the acquired immunodeficiency syndrome (AIDS). In this study, impact of exposure to electromagnetic field (EMF) on the permeability of saquinavir (SQV) across BBB was investigated. The in vitro BBB model was based on human brain-microvascular endothelial cells (HBMEC), and the concentration of SQV in receiver chamber of the transport system was evaluated. Polybutylcyanoacrylate (PBCA), methylmethacrylate-sulfopropylmethacrylate (MMA-SPM), and solid lipid nanoparticle (SLN) were employed as carriers for the delivery systems. Cytotoxicity of SLN decreased as content of cacao butter increased. Power of 5mV was apposite for the study on HBMEC without obvious apoptosis. Square wave produced greater permeability than sine and triangle waves. The carrier order on permeability of SQV across HBMEC monolayer under exposure to EMF was SLN>PBCA>MMA-SPM. Also, a larger frequency, modulation or depth of amplitude modulation (AM), or modulation or deviation of frequency modulation (FM) yielded a greater permeability. Besides, enhancement of permeability by AM wave was more significant than that by FM wave. Transport behavior of SQV across BBB was strongly influenced by the combination of nanoparticulate PBCA, MMA-SPM, and SLN with EMF exposure. This combination would be beneficial to the clinical application to the therapy of AIDS and other brain-related diseases. Panminerva Med.  1995 Mar;37(1):22-7.

A magnetic approach to AIDS.

Jacobson JI Source

Institute of Theoretical Physics and Advanced Studies for Biophysical Res, Jupiter, FL 334377-1418, USA.

Abstract

Jacobson Resonance is the unified field equation yielding a frontier vision in magnetotherapy. The possible application to AIDS is considered.

Ankylosing Spondylitis

Rheumatol Int. 2014 Mar;34(3):357-65. doi: 10.1007/s00296-013-2941-7. Epub 2014 Jan 8.

Is magnetotherapy applied to bilateral hips effective in ankylosing spondylitis patients? A randomized, double-blind, controlled study.

Turan Y1, Bayraktar K, Kahvecioglu F, Tastaban E, Aydin E, Kurt Omurlu I, Berkit IK.

Author information

  • 1Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Adnan Menderes University, Ayd?n, Turkey, dryaseminturan@gmail.com.

Abstract

This double-blind, randomized controlled study was conducted with the aim to investigate the effect of magnetic field therapy applied to the hip region on clinical and functional status in ankylosing spondylitis (AS) patients. Patients with AS (n = 66) who were diagnosed according to modified New York criteria were enrolled in this study. Patients were randomly divided in two groups. Participants were randomly assigned to receive magnetic field therapy (2 Hz) (n = 35), or placebo magnetic field therapy (n = 31) each hip region for 20 min. Patients in each group were given heat pack and short-wave treatments applied to bilateral hip regions. Both groups had articular range of motion and stretching exercises and strengthening exercises for surrounding muscles for the hip region as well as breathing and postural exercises by the same physical therapist. These treatment protocols were continued for a total of 15 sessions (1 session per day), and patients were examined by the same physician at months 1, 3 and 6. Visual analogue scale (VAS) pain, VAS fatigue, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrologic Index (BASMI), DFI, Harris hip assessment index and Ankylosing Spondylitis Quality of Life scale (ASQOL) were obtained at the beginning of therapy and at month 1, month 3 and month 6 for each patient. There were no significant differences between groups in the VAS pain, VAS fatigue, morning stiffness, BASDAI, BASFI, BASMI, DFI, Harris hip assessment index and ASQoL at baseline, month 1, month 3 or month 6 (p > 0.05). Further randomized, double-blind controlled studies are needed in order to establish the evidence level for the efficacy of modalities with known analgesic and anti-inflammatory action such as magnetotherapy, particularly in rheumatic disorders associated with chronic pain.

Analgetic Effect – Comparing Magnetic and Laser Stimulation before Oral Surgery

Wiad Lek. 2006;59(9-10):630-3.

Comparison of analgetic effect of magnetic and laser stimulation before oral surgery procedures.

[Article in Polish]

Koszowski R, Smieszek-Wilczewska J, Dawiec G.

Z Katedry i Zakadu Chirurgii Stomatologicznej w Bytomiu Slaskiej Akademii Medycznej w Katowicach. chirstom@slam.katowice.pl

Abstract

Oral surgery procedures are often the cause of painful sensations because of their tissue invasiveness. To avoid these sensations a wide use of nonsteroid antiinflammatory drugs is usually accepted. Because of plenty side effects of these drugs alternative antipain agents are desired. The goal of this study was to assess antipain effect of laser stimulation and alternating magnetic field in oral surgery procedures. Pain sensations in patients during: local anesthetics application, surgical procedure and after it were assessed according to VAS scale. Level of stomatological fear was assessed with the use of Corah’s scale. Achieved results were analyzed statistically. Conclusion of this analysis is that laser stimulation and alternating magnetic field applied directly before oral surgery procedure are effective antipain agents that decrease intra and postoperative sensations. It was observed that patients with high level of stomatological fear had more pain sensations but even in this group laser and magnetic stimulation significantly lowered these complaints.

Analgesia

Electromagn Biol Med.  2012 Dec;31(4):275-84. doi: 10.3109/15368378.2012.662189. Epub 2012 Jun 12.

Analgesic effect of the electromagnetic resonant frequencies derived from the NMR spectrum of morphine.

Verginadis II, Simos YV, Velalopoulou AP, Vadalouca AN, Kalfakakou VP, Karkabounas SCh, Evangelou AM.

Source

Laboratory of Physiology, University of Ioannina, Ioannina, Greece. aevaggel@cc.uoi.gr

Abstract

Exposure to various types of electromagnetic fields (EMFs) affects pain specificity (nociception) and pain inhibition (analgesia). Previous study of ours has shown that exposure to the resonant spectra derived from biologically active substances’ NMR may induce to live targets the same effects as the substances themselves. The purpose of this study is to investigate the potential analgesic effect of the resonant EMFs derived from the NMR spectrum of morphine. Twenty five Wistar rats were divided into five groups: control group; intraperitoneal administration of morphine 10 mg/kg body wt; exposure of rats to resonant EMFs of morphine; exposure of rats to randomly selected non resonant EMFs; and intraperitoneal administration of naloxone and simultaneous exposure of rats to the resonant EMFs of morphine. Tail Flick and Hot Plate tests were performed for estimation of the latency time. Results showed that rats exposed to NMR spectrum of morphine induced a significant increase in latency time at time points (p < 0.05), while exposure to the non resonant random EMFs exerted no effects. Additionally, naloxone administration inhibited the analgesic effects of the NMR spectrum of morphine. Our results indicate that exposure of rats to the resonant EMFs derived from the NMR spectrum of morphine may exert on animals similar analgesic effects to morphine itself.

Photomed Laser Surg. 2010 Jun;28(3):371-7.

Pain threshold improvement for chronic hyperacusis patients in a prospective clinical study.

Zazzio M.

Audio Laser-Kliniken, Flygeln, Hovmantorp, Sweden. audiolaser@mail.nu

Abstract

OBJECTIVE: The aim of this study was to investigate if laser therapy in combination with pulsed electromagnetic field therapy/repetitive transcranial magnetic stimulation (rTMS) and the control of reactive oxygen species (ROS) would lead to positive treatment results for hyperacusis patients.

BACKGROUND DATA: Eight of the first ten patients treated for tinnitus, who were also suffering from chronic hyperacusis, claimed their hyperacusis improved. Based upon that, a prospective, unblinded, uncontrolled clinical trial was planned and conducted. ROS and hyperacusis pain thresholds were measured.

MATERIALS AND METHODS: Forty-eight patients were treated twice a week with a combination of therapeutic laser, rTMS, and the control and adjustment of ROS. A magnetic field of no more than 100 microT was oriented behind the outer ear, in the area of the mastoid bone. ROS were measured and controlled by administering different antioxidants. At every treatment session, 177-504 J of laser light of two different wavelengths was administered toward the inner ear via meatus acusticus.

RESULTS: The improvements were significantly better in the verum group than in a placebo group, where 40% of the patients were expected to have a positive treatment effect. The patients in the long-term follow-up group received significantly greater improvements than the patients in the short-term follow-up group.

CONCLUSION: The treatment is effective in treating chronic hyperacusis.

Plast Reconstr Surg. 2010 Jun;125(6):1620-9.

Effects of pulsed electromagnetic fields on interleukin-1 beta and postoperative pain: a double-blind, placebo-controlled, pilot study in breast reduction patients.

Rohde C, Chiang A, Adipoju O, Casper D, Pilla AA.

Division of Plastic and Reconstructive Surgery, Columbia University Medical Center, New York-Presbyterian Hospital, New York, NY 10032, USA. chr2111@columbia.edu

Abstract

BACKGROUND: Surgeons seek new methods of pain control to reduce side effects and speed postoperative recovery. Pulsed electromagnetic fields are effective for bone and wound repair and pain and edema reduction. This study examined whether the effect of pulsed electromagnetic fields on postoperative pain was associated with differences in levels of cytokines and angiogenic factors in the wound bed.

METHODS: In this double-blind, placebo-controlled, randomized study, 24 patients, undergoing breast reduction for symptomatic macromastia received pulsed electromagnetic field therapy configured to modulate the calmodulin-dependent nitric oxide signaling pathway. Pain levels were measured by a visual analogue scale, and narcotic use was recorded. Wound exudates were analyzed for interleukin (IL)-1 beta, tumor necrosis factor-alpha, vascular endothelial growth factor, and fibroblast growth factor-2.

RESULTS: Pulsed electromagnetic fields produced a 57 percent decrease in mean pain scores at 1 hour (p < 0.01) and a 300 percent decrease at 5 hours (p < 0.001), persisting to 48 hours postoperatively in the active versus the control group, along with a concomitant 2.2-fold reduction in narcotic use in active patients (p = 0.002). Mean IL-1 beta concentration in the wound exudates of treated patients was 275 percent lower (p < 0.001). There were no significant differences found for tumor necrosis factor-alpha, vascular endothelial growth factor, or fibroblast growth factor-2 concentrations.

CONCLUSIONS: Pulsed electromagnetic field therapy significantly reduced postoperative pain and narcotic use in the immediate postoperative period. The reduction of IL-1 beta in the wound exudate supports a mechanism that may involve manipulation of the dynamics of endogenous IL-1 beta in the wound bed by means of a pulsed electromagnetic field effect on nitric oxide signaling, which could impact the speed and quality of wound repair.

Indian J Exp Biol. 2009 Dec;47(12):939-48.

Low frequency pulsed electromagnetic field–a viable alternative therapy for arthritis.

Ganesan K, Gengadharan AC, Balachandran C, Manohar BM, Puvanakrishnan R.

Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai 600 020, India.

Abstract

Arthritis refers to more than 100 disorders of the musculoskeletal system. The existing pharmacological interventions for arthritis offer only symptomatic relief and they are not definitive and curative. Magnetic healing has been known from antiquity and it is evolved to the present times with the advent of electromagnetism. The original basis for the trial of this form of therapy is the interaction between the biological systems with the natural magnetic fields. Optimization of the physical window comprising the electromagnetic field generator and signal properties (frequency, intensity, duration, waveform) with the biological window, inclusive of the experimental model, age and stimulus has helped in achieving consistent beneficial results. Low frequency pulsed electromagnetic field (PEMF) can provide noninvasive, safe and easy to apply method to treat pain, inflammation and dysfunctions associated with rheumatoid arthritis (RA) and osteoarthritis (OA) and PEMF has a long term record of safety. This review focusses on the therapeutic application of PEMF in the treatment of these forms of arthritis. The analysis of various studies (animal models of arthritis, cell culture systems and clinical trials) reporting the use of PEMF for arthritis cure has conclusively shown that PEMF not only alleviates the pain in the arthritis condition but it also affords chondroprotection, exerts antiinflammatory action and helps in bone remodeling and this could be developed as a viable alternative for arthritis therapy.

Int J Diabetes Dev Ctries. 2009 Apr;29(2):56-61.

Evaluation of the efficacy of pulsed electromagnetic field in the management of patients with diabetic polyneuropathy.

Graak V, Chaudhary S, Bal BS, Sandhu JS.

Department of Sports Medicine and Physiotherapy, Guru Nanak Dev University, Amritsar, Punjab, India.

Abstract

AIM: The study was carried out to evaluate and compare the effect of low power, low frequency pulsed electromagnetic field (PEMF) of 600 and 800 Hz, respectively, in management of patients with diabetic polyneuropathy. SETTINGS AND

DESIGNS: The study was a randomized controlled trial performed in Guru Nanak Dev University and Medical College, Amritsar, India with different subject experimental design.

MATERIALS AND METHODS: Thirty subjects within an age group of 40-68 years with diabetic polyneuropathy stages N1a, N1b, N2a were randomly allocated to groups 1, 2, 3 with 10 subjects in each. Group 1 and 2 were treated with low power 600 and 800-Hz PEMF for 30 min for 12 consecutive days. Group 3 served as control on usual medical treatment of diabetic polyneuropathy (DPN). The subjects with neuropathy due to any cause other than diabetes were excluded. The pain and motor nerve conduction parameters (distal latency, amplitude, nerve conduction velocity) were assessed before and after treatment.

STATISTICAL ANALYSIS: Related t-test and unrelated t-test were used for data analysis.

RESULTS: Significant reduction in pain and statistically significant (P<0.05) improvement in distal latency and nerve conduction velocity were seen in experimental group 1 and 2.

CONCLUSIONS: Low-frequency PEMF can be used as an adjunct in reducing neuropathic pain as well as for retarding the progression of neuropathy in a short span of time.

Bioelectromagnetics. 2008 May;29(4):284-95.

Electromagnetic millimeter wave induced hypoalgesia: frequency dependence and involvement of endogenous opioids.

Radzievsky AA, Gordiienko OV, Alekseev S, Szabo I, Cowan A, Ziskin MC.

Center for Biomedical Physics, Temple University Medical School, Philadelphia, Pennsylvania 19140, USA. aradziev@temple.edu

Abstract

Millimeter wave treatment (MMWT) is based on the systemic biological effects that develop following local skin exposure to low power electromagnetic waves in the millimeter range. In the present set of experiments, the hypoalgesic effect of this treatment was analyzed in mice. The murine nose area was exposed to MMW of “therapeutic” frequencies: 42.25, 53.57, and 61.22 GHz. MMWT-induced hypoalgesia was shown to be frequency dependent in two experimental models: (1) the cold water tail-flick test (chronic non-neuropathic pain), and (2) the wire surface test (chronic neuropathic pain following unilateral constriction injury to the sciatic nerve). Maximum hypoalgesic effect was obtained when the frequency was 61.22 GHz. Other exposure parameters were: incident power density = 13.3 mW/cm(2), duration of each exposure = 15 min. Involvement of delta and kappa endogenous opioids in the MMWT-induced hypoalgesia was demonstrated using selective blockers of delta- and kappa-opioid receptors and the direct ELISA measurement of endogenous opioids in CNS tissue. Possible mechanisms of the effect and the perspectives of the clinical application of MMWT are discussed.

Aesthetic Plast Surg. 2008 Jul;32(4):660-6. Epub 2008 May 28.

Effects of pulsed electromagnetic fields on postoperative pain: a double-blind randomized pilot study in breast augmentation patients.

Hedén P, Pilla AA.

Department of Plastic Surgery, Akademikliniken, Storängsvägen 10, 115 42, Stockholm, Sweden. per.heden@ak.se

Abstract

BACKGROUND: Postoperative pain may be experienced after breast augmentation surgery despite advances in surgical techniques which minimize trauma. The use of pharmacologic analgesics and narcotics may have undesirable side effects that can add to patient morbidity. This study reports the use of a portable and disposable noninvasive pulsed electromagnetic field (PEMF) device in a double-blind, randomized, placebo-controlled pilot study. This study was undertaken to determine if PEMF could provide pain control after breast augmentation.

METHODS: Forty-two healthy females undergoing breast augmentation for aesthetic reasons entered the study. They were separated into three cohorts, one group (n = 14) received bilateral PEMF treatment, the second group (n = 14) received bilateral sham devices, and in the third group (n = 14) one of the breasts had an active device and the other a sham device. A total of 80 breasts were available for final analysis. Postoperative pain data were obtained using a visual analog scale (VAS) and pain recordings were obtained twice daily through postoperative day (POD) 7. Postoperative analgesic medication use was also followed.

RESULTS: VAS data showed that pain had decreased in the active cohort by nearly a factor of three times that for the sham cohort by POD 3 (p < 0.001), and persisted at this level to POD 7. Patient use of postoperative pain medication correspondingly also decreased nearly three times faster in the active versus the sham cohorts by POD 3 (p < 0.001).

CONCLUSION: Pulsed electromagnetic field therapy, adjunctive to standard of care, can provide pain control with a noninvasive modality and reduce morbidity due to pain medication after breast augmentation surgery.

Knee Surg Sports Traumatol Arthrosc. 2007 Jul;15(7):830-4. Epub 2007 Feb 28.

Effects of pulsed electromagnetic fields on patients’ recovery after arthroscopic surgery: prospective, randomized and double-blind study.

Zorzi C, Dall’Oca C, Cadossi R, Setti S.

“Sacro Cuore Don Calabria” Hospital, Via don A. Sempreboni 5, 37024 Negrar (Vr), Italy.

Abstract

Severe joint inflammation following trauma, arthroscopic surgery or infection can damage articular cartilage, thus every effort should be made to protect cartilage from the catabolic effects of pro-inflammatory cytokines and stimulate cartilage anabolic activities. Previous pre-clinical studies have shown that pulsed electromagnetic fields (PEMFs) can protect articular cartilage from the catabolic effects of pro-inflammatory cytokines, and prevent its degeneration, finally resulting in chondroprotection. These findings provide the rational to support the study of the effect of PEMFs in humans after arthroscopic surgery. The purpose of this pilot, randomized, prospective and double-blind study was to evaluate the effects of PEMFs in patients undergoing arthroscopic treatment of knee cartilage. Patients with knee pain were recruited and treated by arthroscopy with chondroabrasion and/or perforations and/or radiofrequencies. They were randomized into two groups: a control group (magnetic field at 0.05 mT) and an active group (magnetic field of 1.5 mT). All patients were instructed to use PEMFs for 90 days, 6 h per day. The patients were evaluated by the Knee injury and Osteoarthritis Outcome Score (KOOS) test before arthroscopy, and after 45 and 90 days. The use of non-steroidal anti-inflammatory drugs (NSAIDs) to control pain was also recorded. Patients were interviewed for the long-term outcome 3 years after arthroscopic surgery. Thirty-one patients completed the treatment. KOOS values at 45 and 90 days were higher in the active group and the difference was significant at 90 days (P < 0.05). The percentage of patients who used NSAIDs was 26% in the active group and 75% in the control group (P = 0.015). At 3 years follow-up, the number of patients who completely recovered was higher in the active group compared to the control group (P < 0.05). Treatment with I-ONE aided patient recovery after arthroscopic surgery, reduced the use of NSAIDs, and also had a positive long-term effect.

Neurosci Biobehav Rev. 2007;31(4):619-42. Epub 2007 Feb 14.

Pain perception and electromagnetic fields.

Del Seppia C, Ghione S, Luschi P, Ossenkopp KP, Choleris E, Kavaliers M.

Institute of Clinical Physiology, National Council of Research, Pisa, Italy. dscri@ifc.cnr.it

Abstract

A substantial body of evidence has accumulated showing that exposure to electromagnetic fields (EMFs) affects pain sensitivity (nociception) and pain inhibition (analgesia). Consistent inhibitory effects of acute exposures to various EMFs on analgesia have been demonstrated in most studies. This renders examinations of changes in the expression of analgesia and nociception a particularly valuable means of addressing the biological effects of and mechanisms underlying the actions of EMFs. Here we provide an overview of the effects of various EMFs on nociceptive sensitivity and analgesia, with particular emphasis on opioid-mediated responses. We also describe the analgesic effects of particular specific EMFs, the effects of repeated exposures to EMFs and magnetic shielding, along with the dependence of EMF effects on lighting conditions. We further consider some of the underlying cellular and biophysical mechanisms along with the clinical implications of these effects of various EMFs.

Wiad Lek. 2006;59(9-10):630-3.

Comparison of analgetic effect of magnetic and laser stimulation before oral surgery procedures.

[Article in Polish]

Koszowski R, Smieszek-Wilczewska J, Dawiec G.

Z Katedry i Zak?adu Chirurgii Stomatologicznej w Bytomiu Slaskiej Akademii Medycznej w Katowicach. chirstom@slam.katowice.pl

Abstract

Oral surgery procedures are often the cause of painful sensations because of their tissue invasiveness. To avoid these sensations a wide use of nonsteroid antiinflammatory drugs is usually accepted. Because of plenty side effects of these drugs alternative antipain agents are desired. The goal of this study was to assess antipain effect of laser stimulation and alternating magnetic field in oral surgery procedures. Pain sensations in patients during: local anesthetics application, surgical procedure and after it were assessed according to VAS scale. Level of stomatological fear was assessed with the use of Corah’s scale. Achieved results were analyzed statistically. Conclusion of this analysis is that laser stimulation and alternating magnetic field applied directly before oral surgery procedure are effective antipain agents that decrease intra and postoperative sensations. It was observed that patients with high level of stomatological fear had more pain sensations but even in this group laser and magnetic stimulation significantly lowered these complaints.

Evid Based Complement Alternat Med. 2006 Jun;3(2):201-7. Epub 2006 Apr 24.

Low-intensity electromagnetic millimeter waves for pain therapy.

Usichenko TI, Edinger H, Gizhko VV, Lehmann C, Wendt M, Feyerherd F.

Abstract

Millimeter wave therapy (MWT), a non-invasive complementary therapeutic technique is claimed to possess analgesic properties. We reviewed the clinical studies describing the pain-relief effect of MWT. Medline-based search according to review criteria and evaluation of methodological quality of the retrieved studies was performed. Of 13 studies, 9 of them were randomized controlled trials (RCTs), only three studies yielded more than 3 points on the Oxford scale of methodological quality of RCTs. MWT was reported to be effective in the treatment of headache, arthritic, neuropathic and acute postoperative pain. The rapid onset of pain relief during MWT lasting hours to days after, remote to the site of exposure (acupuncture points), was the most characteristic feature in MWT application for pain relief. The most commonly used parameters of MWT were the MW frequencies between 30 and 70 GHz and power density up to 10 mW cm(-2). The promising results from pilot case series studies and small-size RCTs for analgesic/hypoalgesic effects of MWT should be verified in large-scale RCTs on the effectiveness of this treatment method.

Australas Psychiatry. 2005 Sep;13(3):258-65.

Transcranial magnetic stimulation and chronic pain: current status.

Pridmore S, Oberoi G, Marcolin M, George M.

Division of Psychiatry, University of Tasmania, Hobart, Tas., Australia. spridmore@iprimus.com.au

OBJECTIVE: To examine evidence suggesting a potential role for transcranial magnetic stimulation (TMS) in the treatment of chronic pain. CONCLUSION: Chronic pain is characterized by brain changes that can reasonably be presumed to be associated with hyperalgesia, as occurs with neuropathic changes in the periphery. TMS has the ability to induce plastic changes in the cortex at the site of stimulation and at connected sites, including the spinal cord. It also has the ability to influence the experience of experimental/acute pain. In studies of TMS in chronic pain, there is some evidence that temporary relief can be achieved in a proportion of sufferers. Chronic pain is common. Current treatments are often ineffective and complicated by side-effects. Work to this point is encouraging, but systematic assessment of stimulation parameters is necessary if TMS is to achieve a role in the treatment of chronic pain. Maintenance TMS is currently provided in relapsing major depression and may be a useful model in chronic pain management.

Bioelectromagnetics. 2004 Sep;25(6):466-73.

Millimeter wave-induced suppression of B16 F10 melanoma growth in mice: involvement of endogenous opioids.

Radzievsky AA, Gordiienko OV, Szabo I, Alekseev SI, Ziskin MC.

Center for Biomedical Physics, Temple University Medical School, Philadelphia, Pennsylvania 19140, USA. aradziev@temple.edu

Abstract

Millimeter wave treatment (MMWT) is widely used in Eastern European countries, but is virtually unknown in Western medicine. Among reported MMWT effects is suppression of tumor growth. The main aim of the present “blind” and dosimetrically controlled experiments was to evaluate quantitatively the ability of MMWT to influence tumor growth and to assess whether endogenous opioids are involved. The murine experimental model of B16 F10 melanoma subcutaneous growth was used. MMWT characteristics were: frequency, 61.22 GHz; average incident power density, 13.3 x 10(-3) W/cm2; single exposure duration, 15 min; and exposure area, nose. Naloxone (1 mg/kg, intraperitoneally, 30 min prior to MMWT) was used as a nonspecific blocker of opioid receptors. Five daily MMW exposures, if applied starting at the fifth day following B16 melanoma cell injection, suppressed subcutaneous tumor growth. Pretreatment with naloxone completely abolished the MMWT-induced suppression of melanoma growth. The same course of 5 MMW treatments, if started on day 1 or day 10 following tumor inoculations, was ineffective. We concluded that MMWT has an anticancer therapeutic potential and that endogenous opioids are involved in MMWT-induced suppression of melanoma growth in mice. However, appropriate indications and contraindications have to be developed experimentally before recommending MMWT for clinical usage.

Neurosci Lett. 2004 Jun 10;363(2):157-62.

Human exposure to a specific pulsed magnetic field: effects on thermal sensory and pain thresholds.

Shupak NM, Prato FS, Thomas AW.

Department of Nuclear Medicine, St Joseph’s Health Care, London, Ontario, Canada.

Exposure to pulsed magnetic fields (MF) has been shown to have a therapeutic benefit in both animals (e.g. mice, snails) and humans. The current study investigated the potential analgesic benefit of MF exposure on sensory and pain thresholds following experimentally induced warm and hot sensations. Thirty-nine subjects (Study 1) and 31 subjects (Study 2) were randomly and double-blindly assigned to 30 min of MF or sham exposure between two sets of tests of sensory and pain thresholds and latencies at, 1 degrees C above, and 2 degrees C above pain thresholds. Results indicated that MF exposure does not affect sensory thresholds [e.g. [F(1,31) = 0.073, NS]. Pain thresholds were significantly increased following MF exposure [F(1,6) = 9.45, P < 0.01] but not following sham exposure [F (1,4) = 4.22, NS]. A significant condition by gender interaction existed for post-exposure pain thresholds [F(1,27) = 5.188, P < 0.05]. Taken together, these results indicate that MF exposure does not affect basic human perception, but can increase pain thresholds in a manner indicative of an analgesic response. The potential involvement of the placebo effect is discussed.

Suppl Clin Neurophysiol. 2004;57:737-48.

Transcranial magnetic stimulation in the management of pain.

Lefaucheur JP.

Service de Physiologie, Explorations Fonctionnelles, Hopital Henri Mondor, Assistance Publique, Hopitaux de Paris, INSERM U421, Faculte de Medecine de Creteil, 94010 Creteil, France. jean-pascal.lefaucheur@hmn.ap-hop-paris.fr

Drug-resistant, neurogenic pain can be treated by chronic motor cortex stimulation using surgically-implanted epidural electrodes. High-frequency, subthreshold repetitive transcranial magnetic stimulation (rTMS) of the motor cortex was shown to be able to produce antalgic effects, at least transiently, in patients with chronic pain. Nevertheless, other cortical targets than the primary motor cortex are tempting (parietal or prefrontal areas for instance) for the management of pain and need to be studied. Motor cortex TMS was also found to modulate non-nociceptive sensory perception as well as acutely provoked pain in healthy subjects by means of a single conditioning pulse or repeated trains. On the contrary, spontaneous or provoked pain was shown to modify motor cortex excitability, as assessed by TMS technique. Taking into account all these observations, it appears that motor cortex function and pain process are closely related and that TMS is a potent tool to explore and to understand this relationship. Beyond this physiological purpose, rTMS could be useful to control episodes of neurogenic pain of limited duration or to select patients for the surgical implantation of a cortical stimulator.

Neurosci Lett. 2004 Jan 2;354(1):30-3.

Analgesic and behavioral effects of a 100 microT specific pulsed extremely low frequency magnetic field on control and morphine treated CF-1 mice.

Shupak NM, Hensel JM, Cross-Mellor SK, Kavaliers M, Prato FS, Thomas AW.

Bioelectromagnetics, Lawson Health Research Institute, Department of Nuclear Medicine, St. Joseph’s Health Care, 268 Grosvenor Street, London, Ont. N6A 4V2, Canada.

Abstract

Diverse studies have shown that magnetic fields can affect behavioral and physiological functions. Previously, we have shown that sinusoidal extremely low frequency magnetic fields and specific pulsed magnetic fields (Cnps) can produce alterations in the analgesia-related behavior of the land snail. Here, we have extended these studies to show an induction of analgesia in mice equivalent to a moderate dose of morphine (5 mg/kg), and the effect of both Cnp exposure and morphine injection on some open-field activity. Cnp exposure was found to prolong the response latency to a nociceptive thermal stimulus (hot plate). Cnp+morphine offset the increased movement activity found with morphine alone. These results suggest that pulsed magnetic fields can induce analgesic behavior in mice without the side effects often associated with opiates like morphine.

Acupunct Electrother Res. 2003;28(1-2):11-8.

Treatment of rheumatoid arthritis with electromagnetic millimeter waves applied to acupuncture points–a randomized double blind clinical study.

Usichenko TI, Ivashkivsky OI, Gizhko VV.

Anesthesiology & Intensive Care Medicine Department, University of Greifswald, Germany. taras@uni-greifswald.de

Abstract

The aim of the study was to evaluate the efficacy and safety of electromagnetic millimeter waves (MW) applied to acupuncture points in patients with rheumatoid arthritis (RA). Twelve patients with RA were exposed to MW with power 2.5 mW and band frequency 54-64 GHz. MW were applied to the acupuncture points of the affected joints in a double blind manner. At least 2 and maximum 4 points were consecutively exposed to MW during one session. Total exposure time consisted of 40 minutes. According to the study design, group I received only real millimeter wave therapy (MWT) sessions, group II only sham sessions. Group III was exposed to MW in a random cross-over manner. Pain intensity, joint stiffness and laboratory parameters were recorded before, during and immediately after the treatment. The study was discontinued because of beneficial therapeutic effects of MWT. Patients from group I (n=4) reported significant pain relief and reduced joint stiffness during and after the course of therapy. Patients from group II (n=4) revealed no improvement during the study. Patients from group III reported the changes of pain and joint stiffness only after real MW sessions. After further large-scale clinical investigations MWT may become a non-invasive adjunct in therapy of patients with RA.

Eur J Pain. 2003;7(3):289-94.

Treatment of chronic pain with millimetre wave therapy (MWT) in patients with diffuse connective tissue diseases: a pilot case series study.

Usichenko TI, Herget HF.

Department of Anaesthesiology and Intensive Care, Ernst Moritz Arndt University, Friedrich Loeffler Strasse 23b, 17487 Greifswald, Germany.taras@uni-greifswald.de

Abstract

BACKGROUND: Pain relief is reported to be the most common clinical application of electromagnetic millimetre waves.

AIM: To evaluate safety and pain relief effect of millimetre wave therapy (MWT) for treatment of chronic joint pain in a group of patients with diffuse connective tissue diseases.

METHODS: Twelve patients with diffuse connective tissue diseases received MWT in addition to their analgesic medication with non-steroidal anti-inflammatory drugs. MWT procedure included the exposure of tender points around the painful joints to electromagnetic waves with frequency 54-78GHz and power density of 2.5mW/cm(2). The time of exposure was 35 +/-5 min and the total number of sessions ranged from 5 to 10 (median 6). Intensity of pain, medication requirement, joint stiffness and subjective assessment of therapy success were measured before, during and immediately after the treatment, and after a 6-months follow-up.

RESULTS: No adverse effects of MWT were noted. Pain intensity and required medication decreased significantly after the treatment (p<0.05) and remained at the same level throughout the follow-up period. The joint stiffness decreased and the subjective assessment of the treatment success after 6 month did not change except in only one patient.

CONCLUSION: MWT applied to tender points around the affected joints was safe under the conditions of our study and after an appropriate full-scale double-blind clinical study, may be recommended as an effective adjunct therapy for chronic pain treatment in patients with diffuse connective tissue diseases.

Percept Mot Skills. 2002 Oct;95(2):592-8.

Increased analgesia to thermal stimuli in rats after brief exposures to complex pulsed 1 microTesla magnetic fields.

Ryczko MC, Persinger MA.

Behavioral Neuroscience Program, Laurentian University, Sudbury, ON, Canada.

Nociceptive thresholds to a 55 degrees C hot surface were measured for female Wistar rats before treatments and 30 min. and 60 min. after the treatments. After injection with either naloxone or saline following baseline measurements, the rats were exposed for 30 min. to either sham fields or to weak (about 1 microTesla) burst-firing magnetic fields composed of 230 points (4 msec. per point) presented once every 3 sec. The rats that had received the burst-firing magnetic fields exhibited elevated nociceptive thresholds that explained about 50% of the variance. A second pattern, designed after the behaviour of individual thalamic neurons during nociceptive input and called the “activity rhythm magnetic field” produced only a transient analgesic effect. These results replicated previous studies and suggest that weak, extremely low frequency, pulsed magnetic fields with biorelevant temporal structures may have utility as adjuncts for treatment of pain.

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2001 Dec;18(4):552-3, 572.

Analgesic effect induced by stimulation of rats brain with strong pulsed magnetic field: a preliminary study.

[Article in Chinese]

Wang Y, Niu J. Shen Q, Jiang D.

Institute of Biomedical Engineering, Xi’an Jiaotong University, Xi’an 710049.

The Objective of this study was to determine whether stimulation on the brain of SD rats with strong pulsed magnetic field could produce analgesic effect. A stimulator of CADWELL (MES-10) was adopted in the study. The pain index used was the Tail Flick Latency (TFL) of rats. The stimulation parameters were: (1) the intensity percent (20%) and stimulation duration (7 min); (2) the intensity percent (30%) and stimulation duration (3 min). The results showed that the mean Acquired TFL change was 23% (P < 0.01) for the 20% intensity group, and 26% (P < 0.01) for the 30% intensity group. CONCLUSION: These data indicate that the new method for analgesia is effective, and compared with other approaches to stimulation analgesia, this one is non-invasive, easy to operate, and less causative of discomfort.

Life Sci. 2001 Jan 26;68(10):1143-51.

Peripheral neural system involvement in hypoalgesic effect of electromagnetic millimeter waves.

Radzievsky AA, Rojavin MA, Cowan A, Alekseev SI, Radzievsky AA Jr, Ziskin MC.

Center for Biomedical Physics, Temple University School of Medicine, Philadelphia, PA 19140, USA. aradziev@temple.edu

Abstract

In a series of blind experiments, using the cold water tail-flick test (cTFT) as a quantitative indicator of pain, the hypoalgesic effect of a single exposure of mice to low power electromagnetic millimeter waves (MW) was studied. The MW exposure characteristics were: frequency = 61.22 GHz; incident power density = 15 mW/cm2; and duration = 15 min. MW treatment was applied to the glabrous skin of the footpad. Exposure of an intact murine paw to the MW resulted in a statistically significant hypoalgesia as measured in the cTFT. These mice were able to resist cold noxious stimulation in the cTFF more than two times longer than animals from the sham-exposed group. A unilateral sciatic nerve transection was used to deafferent the area of exposure in animals from one of the experimental groups. This surgery, conducted six days before the MW treatment, completely abolished the hypoalgesic effect of the exposure to MW. The results obtained support the conclusion that the MW-skin nerve endings interaction is the essential step in the initiation of biological effects caused by MW. Based on our past and present results we recommend that in order to obtain a maximum therapeutic effect, densely innervated skin areas (head, hands) need to be used preferentially for exposure to MW in clinical practice.

Vopr Kurortol Fizioter Lech Fiz Kult. 2000 Jul-Aug;(4):7-11.

Pain relief by low-intensity frequency-modulated millimeter waves acting on the acupuncture points.

[Article in Russian]

Samosiuk IZ, Kulikovich IuN, Tamarova ZA, Samosiuk NI, Kazhanova AK.

Abstract

Analgetic effect of low-intensive frequency-modulated millimetric waves (MW) was studied in mice with formalin induced nociceptive behavior reaction (licking of defeat hindpaw). MW were applied to the acupoint E 36 of the defeat hindpaw. The following MW were used: 60 GHz (1) and 118 GHz (2) which were modulated by 4 Hz; noise MW within the range of 42-95 GHz (3) and 90-140 GHz (4) which were modulated in accidental order by frequencies 1-60 Hz; combinations of fixed frequencies with noise – 60 GHz + noise 42-95 GHz (5) and 118 GHz + noise 90-140 GHz (6). All used MW combinations suppressed licking of the defeat hindpaw and increased duration of sleep and eating. The strongest analgesia was achieved in series 1-3 (42.4-69.7%), the weakest in series 6 and 4 of the experiment (12.2-19.7%).

Int J Radiat Biol. 2000 Apr;76(4):575-9.

Pain relief caused by millimeter waves in mice: results of cold water tail flick tests.

Rojavin MA, Radzievsky AA, Cowan A, Ziskin MC.

Richard J Fox Center for Biomedical Physics, Philadelphia, PA 19140, USA.

Abstract

PURPOSE: To find out if millimeter waves can decrease experimental pain response in mice using cold water tail flick test.

MATERIALS AND METHODS: Male Swiss albino mice (15 mice per group) were exposed to continuous millimeter waves at a frequency of 61.22 GHz with incident power densities (IPD) ranging from 0.15 to 5.0 mW/cm2 for 15 min or sham exposed. Latency of tail withdrawal in a cold water (1 +/- 0.5 degrees C) tail flick test was measured before the exposure (baseline) and then four times after the exposure with 15 min breaks.

RESULTS: The mean latency of the tail flick response in mice exposed to millimeter waves was more than twice that of sham-exposed controls (p<0.05). This effect was proportional to the power of millimeter waves and completely disappeared at an IPD level of < or = 0.5 mW/cm2. Pretreatment of mice with the opioid antagonist naloxone (1 mg/kg i.p.) blocked the effect of millimeter waves.

CONCLUSIONS: Results suggest that the antinociceptive effect of millimeter waves is mediated through endogenous opioids.

Life Sci. 2000 Apr 14;66(21):2101-11.

Hypoalgesic effect of millimeter waves in mice: dependence on the site of exposure.

Radzievsky AA, Rojavin MA, Cowan A, Alekseev SI, Ziskin MC.

Center for Biomedical Physics, Temple University School of Medicine, Philadelphia, PA 19140, USA. aradziev@temple.edu

Abstract

Based on a hypothesis of neural system involvement in the initial absorption and further processing of the millimeter electromagnetic waves (MW) signal, we reproduced, quantitatively assessed and compared the analgesic effect of a single MW treatment, exposing areas of skin possessing different innervation densities. The cold water tail flick test (cTFT) was used to assess experimental pain in mice. Three areas of exposure were used: the nose, the glabrous skin of the right footpad, and the hairy skin of the mid back at the level of T5-T10. The MW exposure characteristics were: frequency = 61.22 GHz; incident power density = 15mW/cm2; and duration = 15 min. The maximum hypoalgesic effect was achieved by exposing to MW the more densely innervated skin areas–the nose and the footpad. The hypoalgesic effect in the cTFT after MW exposure to the murine back, which is less densely innervated, was not statistically significant. These results support the hypothesis of neural system involvement in the systemic response to MW.

Int J Radiat Biol. 1997 Oct;72(4):475-80.

Electromagnetic millimeter waves increase the duration of anaesthesia caused by ketamine and chloral hydrate in mice.

Rojavin MA, Ziskin MC.

Richard J. Fox Center for Biomedical Physics, Temple University School of Medicine, Philadelphia, PA 19140, USA.

Abstract

BALB/c mice were injected i.p. with either ketamine 80 mg/kg or chloral hydrate 450 mg/kg. Anaesthetized mice were exposed to unmodulated electromagnetic millimeter waves at the frequency of 61.22 GHz with a peak specific absorption rate of 420 W/kg and corresponding incident power density of 15 mW/cm2 for 15 min or sham-exposed. In combination with either of the anaesthetics used, mm waves increased the duration of anaesthesia by approximately 50% (p < 0.05) in a dose (power)-dependent manner. Sham exposure to mm waves did not affect the sleeping time of mice. Pretreatment of mice with naloxone, an opioid antagonist, did not change the duration of anaesthesia caused by the corresponding chemical agent, but completely blocked or decreased the additional effect of mm waves. The data in this study indicates that exposure of mice to mm waves in vivo releases endogenous opioids or enhances the activity of opioid signalling pathway.

Neurosci Lett. 1997 Jan 31;222(2):107-10.

Antinociceptive effects of a pulsed magnetic field in the land snail, Cepaea nemoralis.

Thomas AW, Kavaliers M, Prato FS, Ossenkopp KP.

Neuroscience Program, University of Western Ontario, London, Canada. athomas@Iri.stjoseph-s.london.on.ca

Abstract

Pulsed magnetic fields (patent pending) consisting of approximately 100 microT (peak), frequency modulated, extremely low frequency magnetic fields (ELFMF) were shown to induce a significant degree of antinociception (‘analgesia’) in the land snail Cepaea nemoralis. Fifteen minute exposures to a specific magnetic field both increased enkephalinase inhibitor induced opioid analgesia and induced analgesia in untreated snails. Injection of the prototypic opioid antagonist naloxone, attenuated, but did not completely block, the pulsed magnetic field induced analgesia. Two other pulsed waveform designs failed to induce analgesia in untreated snails. These findings suggest that specific magnetic field exposure designs may be tailored to produce significant behavioral effects including, but certainly not limited to, the induction of analgesia.

FASEB J. 1995 Jun;9(9):807-14.

Possible mechanisms by which extremely low frequency magnetic fields affect opioid function.

Prato FS, Carson JJ, Ossenkopp KP, Kavaliers M.

Department of Medical Biophysics, University of Western Ontario, London, Canada.

Abstract

Although extremely low frequency (ELF, < 300 Hz) magnetic fields exert a variety of biological effects, the magnetic field sensing/transduction mechanism (or mechanisms) remain to be identified. Using the well-defined inhibitory effects that magnetic fields have on opioid peptide mediated antinociception or “analgesia” in the land snail Cepaea nemoralis, we show that these actions only occur for certain frequency and amplitude combinations of time-varying sinusoidal magnetic fields in a manner consistent with a direct influence of these fields. We exposed snails with augmented opioid activity to ELF magnetic fields, which were varied in both amplitude and frequency, along with a parallel static magnetic field. When the peak amplitude (0-547 microT) of a magnetic field of 60 Hz was varied systematically, we observed a nonlinear response, i.e., a nonlinear reduction in analgesia as measured by the latency of a defined response by the snails to a thermal stimulus. When frequency (10-240 Hz) was varied, keeping the amplitude constant (141 microT), we saw significant inhibitory effects between 30 and 35 Hz, 60 and 90 Hz and at 120 and 240 Hz. Finally, when the static field was varied but the amplitude and frequency of the time-varying field were held constant, we observed significant inhibition at almost all amplitudes. This amplitude/frequency “resonance-like” dependence of the magnetic field effects suggests that the mechanism (or mechanisms) of response to weak ELF fields likely involves a direct magnetic field detection mechanism rather than an induced current phenomenon. We examined the implications of our findings for several models proposed for the direct sensing of ELF magnetic fields.

Brain Res. 1993 Aug 20;620(1):159-62.

Repeated naloxone treatments and exposures to weak 60-Hz magnetic fields have ‘analgesic’ effects in snails.

Kavaliers M, Ossenkopp KP.

Bioelectromagnetics Western and Neuroscience Program, University of Western Ontario, London, Canada.

Abstract

Results of studies with rodents have shown that animals repeatedly injected with the opioid antagonist, naloxone, acquire a hypoalgesic response to thermal nociceptive stimuli. The present study revealed a similar response in the terrestrial pulmonate snail, Cepaea nemoralis. Snails receiving daily injections of naloxone followed by measurements of thermal nociceptive sensitivity also developed hypoalgesia. Daily brief (30-min) exposures to a weak 60-Hz magnetic field (1.0 gauss or 0.1 mT), which acutely antagonize opioid-mediated nociception and antinociception in a manner comparable to that of naloxone, also led to the expression of a hypoalgesic responses. This suggests that opioid antagonist-induced thermal hypoalgesia may be a basic feature of opioid systems. This naloxone- and magnetic field-induced ‘analgesia’ is consistent with either a facilitation of aversive thermal conditioning and or antagonism of the excitatory, hyperalgesic effects of low levels of endogenous opioids.

Minerva Anestesiol. 1989 Jul-Aug;55(7-8):295-9.

Pulsed magnetic fields.  Observations in 353 patients suffering from chronic pain

[Article in Italian]

Di Massa A, Misuriello I, Olivieri MC, Rigato M.

Three hundred-fifty-three patients with chronic pain have been treated with pulsed electromagnetic fields. In this work the Authors show the result obtained in the unsteady follow-up (2-60 months). The eventual progressive reduction of benefits is valued by Spearman’s test. We noted the better results in the group of patients with post-herpetic pain (deafferentation) and in patients simultaneously suffering from neck and low back pain.

J Comp Physiol A. 1988 Mar;162(4):551-8.

Magnetic fields inhibit opioid-mediated ‘analgesic’ behaviours of the terrestrial snail, Cepaea nemoralis.

Kavaliers M, Ossenkopp KP.

Division of Oral Biology, Faculty of Dentistry, University of Western Ontario, London, Canada.

Abstract

1. The terrestrial snail, Cepaea nemoralis, when placed on a warmed surface (40 degrees C) displays a thermal avoidance behaviour that entails an elevation of the anterior portion of the fully extended foot. The latency of this nociceptive response was increased by the prototypical mu and specific kappa opiate agonists, morphine and U-50, 488H, respectively, in a manner indicative of anti-nociception and the induction of ‘analgesia’. Pretreatment with the prototypical opiate antagonist, naloxone, blocked the morphine- and reduced the U-50, 488H-induced analgesia. Naloxone had no effects on the thermal response latencies of saline treated animals. 2. Exposure to either cold (7 degrees C) or warm (38 degrees C) temperature stress increased the nociceptive thresholds of Cepaea in a manner indicative of the induction of ‘stress-induced analgesia’. The warm stress-induced analgesia was opioid mediated, being blocked by naloxone, whereas, the cold stress-induced analgesia was insensitive to naloxone. 3. Exposure for 15-30 min to 0.5 Hz weak rotating magnetic fields (1.5-8.0 G) significantly reduced the analgesic effects of the mu and kappa opiate agonists in a manner similar to that observed with naloxone. The magnetic stimuli also inhibited the endogenous opioid mediated warm stress-induced analgesia and significantly reduced the cold stress-induced analgesia. The magnetic stimuli had no evident effects on the nociceptive responses of saline-treated animals. The dihydropyridine (DHP) and non-DHP calcium channel antagonists diltiazem, verapamil. and nifedipine differentially and significantly reduced, while the DHP calcium channel agonist, BAY K8644, significantly enhanced the inhibitory effects of the magnetic fields on morphine-induced analgesia.

Peptides. 1986 May-Jun;7(3):449-53.

Magnetic fields differentially inhibit mu, delta, kappa and sigma opiate-induced analgesia in mice.

Kavaliers M, Ossenkopp KP.

Abstract

An exposure for 60 min to a 0.5 Hz rotating magnetic field (1.5-90 G) significantly attenuated the daytime analgesic effects of the mu and kappa opiate agonists, morphine and U50,488H, respectively, and significantly inhibited the analgesic actions of the delta agonist, D-Ala2-D-Leu5-enkephalin, in mice. The magnetic stimuli had no significant effects on the analgesic effects of the prototypic sigma opiate agonist (+/-) SKF-10,047. These results show that exposure to relatively weak magnetic stimuli has significant and differential inhibitory influences on various opioid systems.