Review article (Meta-analysis)
Repetitive Transcranial Magnetic Stimulation in Chronic Pain: A Review of the Literature

https://doi.org/10.1016/j.apmr.2014.11.010Get rights and content

Abstract

Objective

To review the literature on the analgesic effects of repetitive transcranial magnetic stimulation (rTMS) in chronic pain according to different pain syndromes and stimulation parameters.

Data Sources

Publications on rTMS and chronic pain were searched in PubMed and Google Scholar using the following key words: chronic pain, analgesia, transcranial magnetic stimulation, neuropathic pain, fibromyalgia, and complex regional pain syndrome.

Study Selection

This review only included double-blind, controlled studies with >10 participants in each arm that were published from 1996 to 2014 and written in English. Studies with relevant information for the understanding of the effects of rTMS were also cited.

Data Extraction

The following data were retained: type of pain syndrome, type of study, coil type, target, stimulation intensity, frequency, number of pulses, orientation of induced current, number of session, and a brief summary of intervention outcomes.

Data Synthesis

A total of 33 randomized trials were found. Many studies reported significant pain relief by rTMS, especially high-frequency stimulation over the primary motor cortex performed in consecutive treatment sessions. Pain relief was frequently >30% compared with control treatment. Neuropathic pain, fibromyalgia, and complex regional pain syndrome were the pain syndromes more frequently studied. However, among all published studies, only a few performed repetitive sessions of rTMS.

Conclusions

rTMS has potential utility in the management of chronic pain; however, studies using maintenance sessions of rTMS and assessing the effects of rTMS on the different aspects of chronic pain are needed to provide a more solid basis for its clinical application for pain relief.

Section snippets

Literature search strategy

A search of literature on the analgesic effect of rTMS in chronic pain published from 1996 to 2014 was conducted using databases (Google Scholar and PubMed). Keywords included the following: chronic pain, analgesia, transcranial magnetic stimulation, neuropathic pain, fibromyalgia, and complex regional pain syndrome.

Study selection

The review included double-blind, sham-controlled, or direct comparative studies with >10 participants in each arm and were written in English. Studies with relevant information to

Results

We found 33 randomized trials on the analgesic effect of rTMS. Many studies reported significant relief by rTMS, especially high-frequency stimulation over the primary motor cortex (M1) performed in consecutive treatment sessions. The available studies included 843 patients; of these, 223 (26.4%) had central NeP, and 277 (26.9%) had peripheral NeP. Fibromyalgia was present in 166 (19.7%) patients, and complex regional pain syndrome (CRPS) was present in 35 (4.1%) patients. Other pain syndromes

Evidence for pain relief after rTMS in the different chronic pain syndromes

Most studies reported significant pain relief after rTMS, which was frequently >30% pain reduction compared with the control treatment, especially in studies where rTMS was performed at a high frequency (10Hz) over the M1 and the induced electric current was delivered in the posterior/anterior direction. The main characteristics of the studies, outcome measurements, and stimulation parameters are described in table 1. A critical review of the analgesic effects of rTMS in each of the main pain

Neuropathic pain

NeP affects 7% of the general population and can negatively impact quality of life. It is caused by lesions or disease affecting the peripheral or central nervous system. We found 21 randomized controlled trials that evaluated the analgesic effects of rTMS in approximately 500 patients with NeP. Sixteen studies showed significant pain reduction after rTMS compared with sham or 1Hz stimulation, whereas 5 studies were negative. In NeP treatment trials, 30% pain intensity reduction is frequently

Mechanisms of action of cortical stimulation in pain

Studies on the mechanisms of action of rTMS on pain in animals and patients are scarce, and most of the available data involve experimental pain studies in healthy volunteers.35, 36, 37, 63, 64, 65, 66 Another rich source of information comes from studies on implanted epidural precentral gyrus stimulation in patients and animals under experimental pain models. Implanted epidural stimulation is a different technique from rTMS. However, the available evidence suggests that both techniques may

Conclusions

Studies using maintenance sessions of rTMS and assessing the different aspects of chronic pain and its different symptom profiles are needed to provide a more solid basis for its clinical application in this patient population.

References (109)

  • J.T. Farrar et al.

    Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale

    Pain

    (2001)
  • B. Pleger et al.

    Repetitive transcranial magnetic stimulation of the motor cortex attenuates pain perception in complex regional pain syndrome type I

    Neurosci Lett

    (2004)
  • R. Defrin et al.

    The effect of a series of repetitive transcranial magnetic stimulations of the motor cortex on central pain after spinal cord injury

    Arch Phys Med Rehabil

    (2007)
  • B.S. Kang et al.

    Effect of repetitive transcranial magnetic stimulation over the hand motor cortical area on central pain after spinal cord injury

    Arch Phys Med Rehabil

    (2009)
  • A. Mhalla et al.

    Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia

    Pain

    (2011)
  • F. Fregni et al.

    Clinical effects and brain metabolic correlates in non-invasive cortical neuromodulation for visceral pain

    Eur J Pain

    (2011)
  • H. Picarelli et al.

    Repetitive transcranial magnetic stimulation is efficacious as an add-on to pharmacological therapy in complex regional pain syndrome (CRPS) type I

    J Pain

    (2010)
  • N. André-Obadia 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)
  • J.H. Vranken et al.

    Duloxetine in patients with central neuropathic pain caused by spinal cord injury or stroke: a randomized, double-blind, placebo-controlled trial

    Pain

    (2011)
  • E. Eisenberg et al.

    Evidence for cortical hyperexcitability of the affected limb representation area in CRPS: a psychophysical and transcranial magnetic stimulation study

    Pain

    (2005)
  • K. Hosomi et al.

    Cortical excitability changes after high-frequency repetitive transcranial magnetic stimulation for central poststroke pain

    Pain

    (2013)
  • A. Mhalla et al.

    Alteration of cortical excitability in patients with fibromyalgia

    Pain

    (2010)
  • S. Baudic et al.

    Unilateral repetitive transcranial magnetic stimulation of the motor cortex does not affect cognition in patients with fibromyalgia

    J Psychiatr Res

    (2013)
  • B.S. Galer et al.

    Case reports and hypothesis: a neglect-like syndrome may be responsible for motor disturbance in reflex sympathetic dystrophy

    J Pain Symptom Manage

    (1995)
  • M. Stanton-Hicks

    Complex regional pain syndrome

    Anesthesiol Clin North America

    (2003)
  • T. Forouzanfar et al.

    Treatment of complex regional pain syndrome type I

    Eur J Pain

    (2002)
  • R.S. Taylor et al.

    Spinal cord stimulation for complex regional pain syndrome: a systematic review of the clinical and cost-effectiveness literature and assessment of prognostic factors

    Eur J Pain

    (2006)
  • S. Johnson et al.

    Changes to somatosensory detection and pain thresholds following high frequency repetitive TMS of the motor cortex in individuals suffering from chronic pain

    Pain

    (2006)
  • D.C. de Andrade et al.

    Neuropharmacological basis of rTMS-induced analgesia: the role of endogenous opioids

    Pain

    (2011)
  • V. Mylius et al.

    Modulation of electrically induced pain by paired pulse transcranial magnetic stimulation of the medial frontal cortex

    Clin Neurophysiol

    (2006)
  • F. Nahmias et al.

    Diffuse analgesic effects of unilateral repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers

    Pain

    (2009)
  • R.L. Pagano et al.

    Transdural motor cortex stimulation reverses neuropathic pain in rats: a profile of neuronal activation

    Eur J Pain

    (2011)
  • J.P. Lefaucheur et al.

    Descending volleys generated by efficacious epidural motor cortex stimulation in patients with chronic neuropathic pain

    Exp Neurol

    (2010)
  • L. García-Larrea et al.

    Electrical stimulation of motor cortex for pain control: a combined PET-scan and electrophysiological study

    Pain

    (1999)
  • R. Peyron et al.

    Electrical stimulation of precentral cortical area in the treatment of central pain: electrophysiological and PET study

    Pain

    (1995)
  • E.T. Fonoff et al.

    Antinociception induced by epidural motor cortex stimulation in naïve conscious rats is mediated by the opioid system

    Behav Brain Res

    (2009)
  • M. Hasan et al.

    Somatosensory change and pain relief induced by repetitive transcranial magnetic stimulation in patients with central poststroke pain

    Neuromodulation

    (2014)
  • X. Moisset et al.

    Brain imaging of neuropathic pain

    Neuroimage

    (2007)
  • R.L. Pagano et al.

    Motor cortex stimulation inhibits thalamic sensory neurons and enhances activity of PAG neurons: possible pathways for antinociception

    Pain

    (2012)
  • N.R. França et al.

    Antinociception induced by motor cortex stimulation: somatotopy of behavioral response and profile of neuronal activation

    Behav Brain Res

    (2013)
  • M.J. Millan

    Descending control of pain

    Prog Neurobiol

    (2002)
  • B. Siegfried et al.

    NMDA receptor blockade in the periaqueductal grey prevents stress-induced analgesia in attacked mice

    Eur J Pharmacol

    (1989)
  • M.M. Behbehani et al.

    Evidence that an excitatory connection between the periaqueductal gray and nucleus raphe magnus mediates stimulation produced analgesia

    Brain Res

    (1979)
  • S. Groppa et al.

    A practical guide to diagnostic transcranial magnetic stimulation: report of an IFCN committee

    Clin Neurophysiol

    (2012)
  • D.O. Rumi et al.

    Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study

    Biol Psychiatry

    (2005)
  • E.B. Short et al.

    Ten sessions of adjunctive left prefrontal rTMS significantly reduces fibromyalgia pain: a randomized, controlled pilot study

    Pain

    (2011)
  • A. Hirayama et al.

    Reduction of intractable deafferentation pain by navigation-guided repetitive transcranial magnetic stimulation of the primary motor cortex

    Pain

    (2006)
  • R.A. de Oliveira et al.

    Repetitive transcranial magnetic stimulation of the left premotor/dorsolateral prefrontal cortex does not have analgesic effect on central poststroke pain

    J Pain

    (2014)
  • T. Goto et al.

    Diffusion tensor fiber tracking in patients with central post-stroke pain; correlation with efficacy of repetitive transcranial magnetic stimulation

    Pain

    (2008)
  • D. Ciampi de Andrade et al.

    Into the island: a new technique of non-invasive cortical stimulation of the insula

    Neurophysiol Clin

    (2012)
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    Supported by Pain Center Research from the Department of Neurology, University of São Paulo, São Paulo, Brazil.

    Disclosures: none.

    Galhardoni and Correia contributed equally to this work.

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