title: A randomized, controlled investigation of motor cortex transcranial magnetic stimulation (TMS) effects on quantitative sensory measures in healthy adults: evaluation of TMS device parameters.
abstract: OBJECTIVE
  There is emerging evidence that transcranial magnetic stimulation (TMS) can produce analgesic effects in clinical samples and in healthy adults undergoing experimentally induced pain; and the field of minimally invasive brain stimulation for the management of pain is expanding rapidly. Although motor cortex is the most widely used cortical target for TMS in the management of neuropathic pain, few studies have systematically investigated the analgesic effects of a full range of device parameters to provide initial hints about what stimulation intensities and frequencies are most helpful (or even potentially harmful) to patients. Further, there is considerable inconsistency between studies with respect to laboratory pain measurement procedures, TMS treatment parameters, sophistication of the sham methods, and sample sizes.
  
  
  METHODS
  This study used a sham-controlled, within-subject, cross-over design to examine the effects of 5 different TMS treatment parameters across several quantitative sensory measures in a sample of healthy adult volunteers. Sixty-five participants underwent quantitative sensory testing procedures pre and post-40-minutes of real and sham motor cortex TMS. TMS was delivered at 1 Hz 80% resting motor threshold (rMT), 1 Hz 100% rMT, 10 Hz 80% rMT, 10 Hz 100% rMT, or 50 Hz triplets at 90% of active motor threshold (intermittent theta-burst).
  
  
  RESULTS
  The mean painfulness rating of real TMS stimulation itself was 3.0 (SE=0.36) out of 10 and was significantly greater than zero [t(64)=8.17, P<0.0001]. The sham TMS methods used permitted matching between real and sham TMS-induced scalp sensations and participants were successfully blinded to condition (real versus sham). Findings suggest that the effects of motor cortex TMS on quantitative sensory tests in healthy adults vary across different treatment parameters with the smallest observed effect for intermittent theta-burst stimulation (Cohen's d=0.03) and the largest for 10 Hz 100% rMT (d=0.34).
  
  
  CONCLUSIONS
  Overall, TMS was associated with statistically significant effects on warm and cool sensory thresholds, cold pain thresholds, suprathreshold stimulus unpleasantness ratings, and wind-up pain. With respect to device parameter effects, higher frequency stimulation seems to be associated with the most analgesic and antisensitivity effects with the exception of intermittent theta-burst stimulation. The present findings support several clinical research findings suggesting that higher TMS frequencies tend to be associated with the most clinical benefit in patients with chronic pain.
authors.affiliation: Departments of Psychiatry and Behavioral, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Borckardt
authors.forename: Scott T
authors.initials: ST
authors.lastname: Reeves
authors.forename: Will
authors.initials: W
authors.lastname: Beam
authors.forename: Mark P
authors.initials: MP
authors.lastname: Jensen
authors.forename: Richard H
authors.initials: RH
authors.lastname: Gracely
authors.forename: Sophie
authors.initials: S
authors.lastname: Katz
authors.forename: Arthur R
authors.initials: AR
authors.lastname: Smith
authors.forename: Alok
authors.initials: A
authors.lastname: Madan
authors.forename: David
authors.initials: D
authors.lastname: Patterson
authors.forename: Mark S
authors.initials: MS
authors.lastname: George
mesh_terms: D000328:Adult; D000698:Analgesia / Q000379:methods; D003080:Cold Temperature; D018592:Cross-Over Studies; D005260:Female; D006358:Hot Temperature; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D010146:Pain / Q000175:diagnosis; D059408:Pain Management; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology*; D016037:Single-Blind Method; D013697:Thermosensing / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D055815:Young Adult