Archives of Physical Medicine and Rehabilitation
Volume 90, Issue 7 , Pages 1102-1109 , July 2009

Pulsed Electromagnetic Fields to Reduce Diabetic Neuropathic Pain and Stimulate Neuronal Repair: A Randomized Controlled Trial

Presented in part to the American Academy of Neurology, April 15–16, 2008, Chicago, IL.

  • Michael I. Weintraub, MD

      Affiliations

    • Departments of Neurology and Medicine, New York Medical College, Valhalla, NY
    • Corresponding Author InformationCorrespondence to Michael I. Weintraub, MD, 325 S Highland Ave, Briarcliff, NY 10510
    • ,
  • David N. Herrmann, MD

      Affiliations

    • Department of Neurology, University of Rochester, Rochester, NY
    • ,
  • A. Gordon Smith, MD

      Affiliations

    • Department of Neurology, University of Utah, Salt Lake City, UT
    • ,
  • Misha M. Backonja, MD

      Affiliations

    • Department of Neurology, University of Wisconsin, Madison, WI
    • ,
  • Steven P. Cole, PhD

      Affiliations

    • Department of Psychology, Emory University, Atlanta, GA

References 

  1. Borckardt JJ, Smith AR, Reeves ST, et al. Fifteen minutes of left prefrontal repetitive transcranial magnetic stimulation acutely increases thermal pain thresholds in healthy adults. Pain Res Manag. 2007;12:287–290
  2. Andre-Obadia N, Mertens P, Gueguen A, et al. Pain relief by rTMS (Differential effect of current flow but no specific action on pain subtypes). Neurology. 2008;71:833–840
  3. Topper R, Foltys H, Meister IG, et al. Repetitive transcranial magnetic stimulation of the parietal cortex transiently ameliorates phantom limb pain-like syndrome. Clin Neurophysiol. 2003;114:1521–1530
  4. Schlaier JR, Eichhammer P, Langguth B, et al. Effects of spinal cord stimulation on cortical excitability in patients with chronic neuropathic pain: a pilot study. Eur J Pain. 2007;11:863–868
  5. Lin VW, Hsiao I, Kingery WS. High intensity magnetic stimulation over the lumbosacral spine evokes antinociception in rats. Clin Neurophysiol. 2002;113:1006–1012
  6. Summers J, Johnson S, Pridmore S, Oberoi G. Changes to cold detection and pain thresholds following low and high frequency transcranial magnetic stimulation of the motor cortex. Neurosci Lett. 2004;368:197–200
  7. Leo RJ, Latif T. Repetitive transcranial magnetic stimulation (rTMS) in experimentally induced and chronic neuropathic pain: a review. J Pain. 2007;8:453–459
  8. Khedr EM, Korb H, Kamel NF, et al. Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain. J Neurol Neurosurg Psychiatry. 2005;76:833–838
  9. Lefaucheur JP. New insights into the therapeutic potential of non-invasive transcranial cortical stimulation in chronic neuropathic pain. Pain. 2006;122:11–13
  10. Lefaucheur JP, Drouot X, Menard-Lefaucheur I, et al. Neurogenic pain relief by repetitive magnetic cortical stimulation depends on the origin and the site of pain. J Neurol Neurosurg Psychiatry. 2004;75:612–616
  11. Veves A, Backonja M, Malik RA. Painful diabetic neuropathy: epidemiology, natural history, early diagnosis and treatment options. Pain Med. 2008;9:660–674
  12. Ørstavik J, Namer B, Schmidt R, et al. Abnormal function of C-fibers in patients with diabetic neuropathy. J Neurosci. 2006;26:11287–11294
  13. Waxman SG. The molecular pathophysiology of pain: abnormal expression of sodium channel genes and its contributions to hyperexcitability of primary sensory neurons. Pain. 1999;(Suppl 6):S133–S140
  14. Cummins TR, Sheets PL, Waxman SG. The role of sodium channels in nociception: implications for mechanisms of pain. Pain. 2007;131:243–257
  15. Quasthoff S. The role of axonal ion conductances in diabetic neuropathy: a review. Muscle Nerve. 1998;21:1246–1255
  16. Smith AG, Ramachandran P, Tripp S, Singleton JR. Epidermal nerve innervation in impaired glucose tolerance and diabetic-associated neuropathy. Neurology. 2001;57:1701–1704
  17. Polydefkis M, Griffin JW, McArthur J. New insights into diabetic polyneuropathy. JAMA. 2003;290:1371–1376
  18. Obrosova IG. Update on the pathogenesis of diabetic neuropathy. Curr Diab Rep. 2003;3:439–445
  19. Kennedy JM, Zochodne DW. Impaired peripheral nerve regeneration in diabetes mellitus. J Peripher Nerv Syst. 2005;10:144–157
  20. Ishii DN. Implication of insulin-like growth factors in the pathogenesis of diabetic neuropathy. Brain Res Brain Res Rev. 1995;20:47–67
  21. Jungnickel J, Gransalke K, Timmer M, Growthe C. Fibroblast growth factor receptor 3 signaling regulates injury-related effects in the peripheral nervous system. Mol Cell Neurosci. 2004;25:21–29
  22. Ekersley L, Ansselin AD, Tomlinson DR. Effects of experimental diabetes on axonal and Schwann cell changes in sciatic nerve isografts. Brain Res Mol Brain Res. 2001;92:128–137
  23. Miyauchi A, Kanje M, Danielsen N, Dahlin LV. Role of macrophages in the stimulation and regeneration of sensory nerves by transposed granulation tissue and temporal aspects of the response. Scan J Plast Reconstr Surg. 1997;31:17–23
  24. Veves A, King GL. Can VEGF reverse diabetic neuropathy in human subjects?. J Clin Invest. 2001;107:1215–1218
  25. Devor M. Sodium channels and mechanisms of neuropathic pain. J Pain. 2006;7(Suppl 1):S3–S12
  26. Eichberg J. Protein kinase C changes in diabetes: is the concept relevant to neuropathy?. Int Rev Neurobiol. 2002;50:61–82
  27. Vincent AM, Russell JW, Low P, Feldman EL. Oxidative stress in the pathogenesis of diabetic neuropathy. Endocr Rev. 2004;25:612–628
  28. Pilla AA, Muehsam DJ, Markov MS, Sisken BF. EMF signals and ion/ligand binding kinetics: predictions of bioeffective waveform parameters. Bioelectrochem Bioenerg. 1999;48:27–34
  29. Longo FM, Yang T, Hamilton S, et al. Electromagnetic fields influence NGF activity and levels following sciatic nerve transection. J Neurosci Res. 1999;55:230–237
  30. Fitzsimmons RJ, Ryaby JT, Mohan S, Magee FP, Baylink DJ. Combined magnetic fields increase insulin-like growth factors-II in TE-85 human osteosarcoma dome cell cultures. Endocrinology. 1995;136:3100–3106
  31. Rodeman HP, Bayrenter K, Pfleiderer G. The differentiation of normal and transformed human fibroblast in vitro is influenced by electromagnetic fields. Exp Cell Res. 1989;189:610–621
  32. Eguchi Y, Ogiue-Ikeda M, Ueno S. Control of orientation of rat Schwann cells using an 8-T static magnetic field. Neurosci Lett. 2003;351:130–132
  33. Frahn J, Lantow M, Lupke M, et al. Alteration in cellular functions in mouse macrophages after exposure to 50 Hz magnetic fields. J Cell Biochem. 2006;1:168–177
  34. Zhao M, Bai H, Wang E, Forrester JV, McCaig CD. Electrical stimulation directly induces pre-angiogenic responses in vascular endothelial cells by signaling through VEGF receptors. J Cell Sci. 2004;117:397–405
  35. Markov MS. Magnetic field therapy: a review. Electromagn Biol Med. 2007;26:1–23
  36. McLean MJ, Holcomb RR, Wamil AW, PIckett JD, Cavapol AV. Blockade of sensory action potentials by a static magnetic field in the 10 mT range. Bioelectromagnetics. 1995;16:20–32
  37. Pilla AA. Mechanisms and therapeutic applications of time-varying and static magnetic fields. In:  Barnes F,  Greenebaum B editor. Handbook of biological effects of electromagnetic fields. 3rd ed.. CRC Pr; 2006;
  38. Weintraub MI, Wolfe GI, Barohn RA, et al. Static magnetic field therapy for symptomatic diabetic neuropathy: a randomized, double-blind, placebo-controlled trial. Arch Phys Med Rehabil. 2003;84:736–746
  39. Timmel CR, Till U, Brocklehurst B. Effects of weak magnetic fields on free radical recombination reactions. Mol Phys. 1998;95:71–89
  40. Cantoni O, Sestili P, Fiorani M, Dacha M. The effect of 50 Hz sinusoidal electric and/or magnetic fields on the rate of repair of DNA single/double strand breaks in oxidatively injured cells. Biochem Mol Biol Int. 1995;37:681–689
  41. Sisken BF. Effects of pulsed magnetic fields on neurite outgrowth from chick embryos. Bioelectromagnetics. 1996;17:293–302
  42. Kennedy WR, Wendelschafer-Crabb G, Johnson T. Quantitation of epidermal nerves in diabetic neuropathy. Neurology. 1996;47:1042–1048
  43. McArthur JC, Stocks EA, Hauer P, Cornblath DR, Griffin JW. Epidermal nerve fiber density: normative reference range and diagnostic efficiency. Arc Neurol. 1998;55:1513–1520
  44. Herrmann DN, Griffin JW, Hauer P, Cornblath DR, McArthur JC. Epidermal nerve fiber density and sural nerve morphometry in peripheral neuropathies. Neurology. 1999;53:1634–1640
  45. Kennedy WR, Wendelschafer-Crabb G, Polydefkis M, McArthur JC. Pathology and quantitation of cutaneous innervation. In: 4th ed..  Dyck PJ,  Thomas PK editor. Peripheral neuropathy. 1:Elsevier: Saunders; 2005;p. 869–895
  46. Jensen MP, Friedman M, Bonzo D, Richards P. The validity of the Neuropathic Pain Scale for assessing diabetic neuropathy pain in a clinical trial. Clin J Pain. 2006;22:97–103
  47. Herrmann DN, McDermott MP, Henderson D, et al. Epidermal nerve fiber density, axonal swellings and QST as predictors of HIV distal sensory neuropathy. Muscle Nerve. 2004;29:420–427
  48. Andre-Obadia N, Peyron R, Mertens P, et al. Transcranial magnetic stimulation for pain control: double-blind study of different frequencies against placebo, and correlation with motor cortex stimulation efficacy. Clin Neurophysiol. 2006;117:1536–1544
  49. Gordh TE, Stubhaug A, Jensen TS, et al. Gabapentin in traumatic nerve injury pain: a randomized, double-blind, placebo-controlled, cross-over, multi-center study. Pain. 2008;138:255–266
  50. Dworkin RH, Turk DC, Farrar JT, et al. Core outcome measures for chronic pain clinical trial: IMMPACT recommendations. Pain. 2005;113:9–19
  51. Fregni F, Freedman S, Pasqual-Leone A. Recent advances in the treatment of chronic pain with non-invasive brain stimulation techniques. Lancet. 2007;6:188–191

 Supported by Nu-Magnetics, Inc, who shipped coded devices to various sites under the supervision of a statistician. Nu-Magnetics played no role in the study design, data analysis, interpretation of data, or article development.

 Investigational Review Boards at Phelps Memorial Hospital, Sleepy Hollow, NY, and each participating clinical site approved the study protocol and informed consent forms. The clinical trial was preregistered at www.clinicaltrials.gov (NCT 00123136).

 No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated.

 Reprints are not available from the author.

PII: S0003-9993(09)00217-2

doi: 10.1016/j.apmr.2009.01.019

Archives of Physical Medicine and Rehabilitation
Volume 90, Issue 7 , Pages 1102-1109 , July 2009

Article Tools

* Image Usage & Resolution