Motor Cortex Reorganization and Repetitive Transcranial Magnetic Stimulation for Pain-A Methodological Study

Objectives: 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. Material and 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.