title: The analgesic effect of therapeutic rTMS is not mediated or predicted by comorbid psychiatric or sleep disorders.
abstract: BACKGROUND
  Mechanisms underlying alleviation of neuropathic pain by repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1) and right secondary somatosensory cortex (S2) are only partly known. Patients with chronic neuropathic pain often have comorbidities like depression and sleep problems. Through functional connectivity, rTMS of M1 and S2 may activate dorsolateral prefrontal cortex, the target for treating depression with rTMS. Thus, the analgesic effect of rTMS could be mediated indirectly via improvement of psychiatric comorbidities or sleep. We examined whether rTMS has an independent analgesic effect or whether its clinical benefits depend on effects on mood or sleep. We also evaluated if comorbid psychiatric or sleep disorders predict the treatment outcome.
  
  
  METHODS
  Sixteen patients with chronic drug-resistant neuropathic orofacial pain participated in this randomized controlled crossover rTMS study. Patients' psychiatric history was evaluated by a specialist in psychiatry. Intensity and interference of pain, mood, and the quality of sleep and life were evaluated at baseline and after 2 active (primary somatosensory cortex [S1]/M1 and S2) and placebo rTMS treatments. A logistic regression analysis was done to investigate predictors of treatment outcome.
  
  
  RESULTS
  The analgesic effect of the right S2 stimulation was not associated with improvement of psychiatric conditions or sleep, whereas S1/M1 stimulation improved sleep without significant analgesic effect (P = 0.013-0.046 in sleep scores). Psychiatric and sleep disorders were more common in patients than in the general population (P = 0.000-0.001 in sleep scores), but these comorbidities did not predict the rTMS treatment outcome.
  
  
  CONCLUSIONS
  We conclude that rTMS to the right S2 does not exert its beneficial analgesic effects in chronic neuropathic orofacial pain via indirect improvement of comorbid psychiatric or sleep disorders.
authors.affiliation: Division of Clinical Neuroscience Department of Clinical Neurophysiology Department of Psychiatry, Turku University Hospital, University of Turku, Turku Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki Institute of Dentistry Pain Clinic, Turku University Hospital, University of Turku, Turku, Finland.
authors.forename: Pauliina
authors.initials: P
authors.lastname: Lindholm
authors.forename: Salla
authors.initials: S
authors.lastname: Lamusuo
authors.forename: Tero
authors.initials: T
authors.lastname: Taiminen
authors.forename: Arja
authors.initials: A
authors.lastname: Virtanen
authors.forename: Antti
authors.initials: A
authors.lastname: Pertovaara
authors.forename: Heli
authors.initials: H
authors.lastname: Forssell
authors.forename: Nora
authors.initials: N
authors.lastname: Hagelberg
authors.forename: Satu
authors.initials: S
authors.lastname: Jääskeläinen
mesh_terms: D000328:Adult; D000368:Aged; D000698:Analgesia / Q000379:methods*; D018592:Cross-Over Studies; D005157:Facial Pain / Q000150:complications* / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000150:complications*; D008875:Middle Aged; D009437:Neuralgia / Q000150:complications* / Q000628:therapy*; D016037:Single-Blind Method; D012893:Sleep Wake Disorders / Q000150:complications*; D050781:Transcranial Magnetic Stimulation; D016896:Treatment Outcome