title: Neuropharmacological basis of rTMS-induced analgesia: the role of endogenous opioids.
abstract: We investigated the role of endogenous opioid systems in the analgesic effects induced by repetitive transcranial magnetic stimulation (rTMS). We compared the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) stimulation before and after naloxone or placebo treatment, in a randomized, double-blind crossover design, in healthy volunteers. Three groups of 12 volunteers were selected at random and given active stimulation (frequency 10Hz, at 80% motor threshold intensity, 1500 pulses per session) of the right M1, active stimulation of the right DLPFC, or sham stimulation, during two experimental sessions 2 weeks apart. Cold pain thresholds and the intensity of pain induced by a series of fixed-temperature cold stimuli (5, 10, and 15°C) were used to evaluate the analgesic effects of rTMS. Measurements were made at the left thenar eminence, before and 1 hour after the intravenous injection of naloxone (bolus of 0.1mg/kg followed by a continuous infusion of 0.1mg/kg/h until the end of rTMS) or placebo (saline). Naloxone injection significantly decreased the analgesic effects of M1 stimulation, but did not change the effects of rTMS of the DLPFC or sham rTMS. This study demonstrates, for the first time, the involvement of endogenous opioid systems in rTMS-induced analgesia. The differential effects of naloxone on M1 and DLPFC stimulation suggest that the analgesic effects induced by the stimulation of these 2 cortical sites are mediated by different mechanisms. Endogenous opioids are shown to be involved in the analgesic effects of repetitive transcranial magnetic stimulation of the motor cortex.
authors.affiliation: INSERM U-987, Centre d'Evaluation et de Traitement de la Douleur, Ambroise Paré, Boulogne-Billancourt, France Department of Neurology, Hospital das Clinicas, University of São Paulo, Brazil.
authors.forename: Daniel Ciampi
authors.initials: DC
authors.lastname: de Andrade
authors.forename: Alaa
authors.initials: A
authors.lastname: Mhalla
authors.forename: Frédéric
authors.initials: F
authors.lastname: Adam
authors.forename: Manoel Jacobsen
authors.initials: MJ
authors.lastname: Texeira
authors.forename: Didier
authors.initials: D
authors.lastname: Bouhassira
mesh_terms: D000328:Adult; D000698:Analgesia / Q000379:methods*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000378:metabolism* / Q000503:physiopathology; D018847:Opioid Peptides / Q000502:physiology*; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D059408:Pain Management; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D055815:Young Adult
chemical_list: D018847:Opioid Peptides