title: Motor Cortex Reorganization and Repetitive Transcranial Magnetic Stimulation for Pain-A Methodological Study.
abstract: OBJECTIVE
  Somatotopic reorganization of primary motor cortex (M1) has been described in several neurological conditions associated with chronic pain. We hypothesized that such reorganization impacts on the mechanisms of M1 stimulation induced analgesia and may either compromise the treatment effect of or provide an alternative target site for repetitive transcranial magnetic stimulation (rTMS). The aim of the study was to compare pain relief following rTMS of the standard motor "hotspot" with that of the reorganized area.
  
  
  METHODS
  We used TMS motor mapping in 30 patients to establish the location of the standard motor "hotspot" (site A) and an alternative site located in the reorganized area (site B), both within M1. Where TMS mapping was not possible (N = 8) we determined the location of the two sites using task-related fMRI. We compared the analgesic effect on neuropathic pain of 5 sessions of navigated rTMS applied over (i) site A, (ii) site B, and (iii) occipital fissure (SHAM stimulation site). Total Pain Relief (TOTPAR) was determined as the difference in average weekly pain scores between baseline and following each rTMS cycle, over three weeks.
  
  
  RESULTS
  Data from 27 patients was analyzed. rTMS of sites A and B resulted in greater TOTPAR than that of SHAM. No difference was seen between sites A and B. Responders (≥15% pain relief) were seen in both groups, with partial overlap only. Addition of stimulation over site B improved the responder rate by 58% compared with site A. In an open-label extension study of five sessions of rTMS aimed at the optimized target site, 8/11 responders and 1/12 nonresponders reported pain relief.
  
  
  CONCLUSIONS
  Cortical reorganization may provide a more effective stimulation target for rTMS in some individuals with neuropathic pain.
authors.affiliation: Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, UK. tjn@liv.ac.uk.|Neuroscience Research Unit, The Walton Centre NHS Foundation Trust, Liverpool, UK. tjn@liv.ac.uk.|Sensorymotor Laboratory, Pain Research Institute, Liverpool, UK. tjn@liv.ac.uk.
authors.forename: Turo
authors.initials: T
authors.lastname: Nurmikko
authors.affiliation: Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, UK.|Sensorymotor Laboratory, Pain Research Institute, Liverpool, UK.
authors.forename: Kathryn
authors.initials: K
authors.lastname: MacIver
authors.affiliation: Neuroscience Research Unit, The Walton Centre NHS Foundation Trust, Liverpool, UK.|Sensorymotor Laboratory, Pain Research Institute, Liverpool, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bresnahan
authors.affiliation: Neuroscience Research Unit, The Walton Centre NHS Foundation Trust, Liverpool, UK.|Sensorymotor Laboratory, Pain Research Institute, Liverpool, UK.
authors.forename: Emily
authors.initials: E
authors.lastname: Hird
authors.affiliation: Sensorymotor Laboratory, Pain Research Institute, Liverpool, UK.|School of Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Andrew
authors.identifier: http://orcid.org/0000-0001-7430-9543
authors.initials: A
authors.lastname: Nelson
authors.affiliation: Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, UK.|Sensorymotor Laboratory, Pain Research Institute, Liverpool, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Sacco
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001931:Brain Mapping; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D009437:Neuralgia / Q000000981:diagnostic imaging / Q000473:pathology*; D059408:Pain Management; D010147:Pain Measurement; D011795:Surveys and Questionnaires; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
keywords: Cortical reorganization; functional MRI; motor cortex; neuronavigation; neuropathic pain; transcranial magnetic stimulation