title: From pulses to pain relief: an update on the mechanisms of rTMS-induced analgesic effects.
abstract: BACKGROUND
  Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that allows cortical stimulation. Recent studies have shown that rTMS of the primary motor cortex or dorsolateral prefrontal cortex decreases pain in various pain conditions. The aim of this review was to summarize the main characteristics of rTMS-induced analgesic effects and to analyse the current data on its mechanisms of action.
  
  
  METHODS
  Medline, PubMed and Web of Science were searched for studies on the analgesic effects and mechanisms of rTMS-induced analgesic effects. Studies on epidural motor cortex stimulation (EMCS) were also included when required, as several mechanisms of action are probably shared between both techniques.
  
  
  RESULTS
  Stimulation site and stimulation parameters have a major impact on rTMS-related analgesic effects. Local cortical stimulation is able to elicit changes in the functioning of distant brain areas. These modifications outlast the duration of the rTMS session and probably involve LTP-like mechanisms via its influence on glutamatergic networks. Analgesic effects seem to be correlated to restoration of normal cortical excitability in chronic pain patients and depend on pain modulatory systems, in particular endogenous opioids. Dopamine, serotonin, norepinephrine and GABAergic circuitry may also be involved in its effects, as well as rostrocaudal projections.
  
  
  CONCLUSIONS
  rTMS activates brain areas distant from the stimulation site. LTP-like mechanisms, dependence on endogenous opioids and increase in concentration of neurotransmitters (monoamines, GABA) have all been implicated in its analgesic effects, although more studies are needed to fill in the still existing gaps in the understanding of its mechanisms of action.
authors.affiliation: Inserm U-987, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, Assistance Publique Hôpitaux de Paris, Boulogne Billancourt, France.|Clermont Université, Université d'Auvergne, Neuro-Dol, Inserm U-1107, Clermont-Ferrand, France.|Service de Neurologie, CHU Gabriel Montpied, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: X
authors.initials: X
authors.lastname: Moisset
authors.affiliation: Department of Neurology, Pain Center, University of São Paulo, Brazil.|Transcranial Magnetic Stimulation Laboratory, Instituto de Psiquiatria, University of São Paulo, Brazil.|Instituto do Câncer Octavio Frias de Oliveira, University of São Paulo, Brazil.
authors.forename: D C
authors.initials: DC
authors.lastname: de Andrade
authors.affiliation: Inserm U-987, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, Assistance Publique Hôpitaux de Paris, Boulogne Billancourt, France.|Université Versailles-Saint-Quentin, Versailles, France.
authors.forename: D
authors.initials: D
authors.lastname: Bouhassira
mesh_terms: D001921:Brain / Q000378:metabolism; D059350:Chronic Pain / Q000378:metabolism / Q000628:therapy*; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D017774:Long-Term Potentiation; D009044:Motor Cortex / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D018847:Opioid Peptides / Q000378:metabolism; D059408:Pain Management / Q000379:methods; D017397:Prefrontal Cortex / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018847:Opioid Peptides; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D004298:Dopamine; D009638:Norepinephrine