title: Repetitive transcranial magnetic stimulation induced analgesia depends on N-methyl-D-aspartate glutamate receptors.
abstract: We investigated the role of glutamate N-methyl-d-aspartate (NMDA) receptors in the analgesic effects induced by repetitive transcranial magnetic stimulation (rTMS). In a randomized, double-blind, crossover study, we compared the effects of ketamine and placebo on the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex/premotor cortex (DLPFC/PMC) stimulation. Three groups of 12 healthy volunteers underwent active rTMS (10Hz, 80% resting motor threshold, 1,500 pulses per session) of the right M1, active stimulation of the right DLPFC/PMC, or sham stimulation during 2 experimental sessions 2 weeks apart. Cold pain thresholds were measured on the left thenar eminence before and 1 hour after cortical stimulation, to evaluate the analgesic effects of rTMS. Ketamine (0.15 mg/kg in a 10-minute bolus followed by continuous infusion of 6 μg/kg per minute until the end of rTMS) or placebo (saline) were administered intravenously during cortical stimulation. We also systematically measured cortical excitability parameters (resting motor threshold, suprathreshold motor-evoked potentials, short intracortical inhibition, and intracortical facilitation) before and after treatment, to investigate the possible relationship between changes in cortical excitability and rTMS-induced analgesia. Ketamine injection significantly decreased the analgesic effects of both M1 and DLPFC/PMC stimulation. The decrease in the analgesic effect of rTMS was not associated with changes in cortical excitability parameters, which were not influenced by rTMS following the administration of either saline or ketamine. Thus, rTMS-induced analgesia depends on glutamate NMDA receptors and may involve long-term potentiation-like mechanisms.
authors.affiliation: INSERM U-987, CHU Ambroise Paré, APHP, F-92100 Boulogne-Billancourt, France Department of Neurology, Hospital das Clinicas, University of São Paulo, Brazil Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, SP, Brazil Université Versailles-Saint-Quentin, F-78035 Versailles, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ciampi 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; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage; D008297:Male; D010147:Pain Measurement / Q000379:methods*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D055815:Young Adult
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine
keywords: Analgesia; Chronic pain; Experimental pain; N-methyl-d-aspartate; Neuromodulation; Pain modulation; Psychophysics; rTMS