BackgroundHigh frequency repetitive transcranial magnetic stimulation (rTMS) targetted to different cortical regions (primary motor/sensory, prefrontal) are known to alter somatosensory responses. The mechanism(s) for these effects are unclear. We compared the analgesic effects of rTMS at different cortical sites on hyperalgesia induced using topical capsaicin cream.MethodsFourteen healthy subjects had capsaicin cream applied to a 16 cm2 area of the medial aspect of the right wrist (60 min) on 4 separate occasions over 6 weeks. rTMS (10Hz for 10s/min¿=¿2000 stimuli @ 90% resting motor threshold of first dorsal interosseus muscle) was applied to the optimum site for right hand (M1), left dorsolateral prefrontal (DLFPC) and occipital midline (OCC) in a pseudo-randomised order. Thermal and mechanical perception and pain thresholds were determined using standardised quantitative sensory testing (QST) methods at the capsaicin site. Subjective responses to thermal stimuli (pain score on a numerical rating scale) from ¿2.5°C to +2.5°C of the individualised heat pain threshold (HPT) resulted in a hyperalgesia curve. Sensory testing took place prior to capsaicin application (PRE-CAP), after 30 min of capsaicin (POST-CAP) and following rTMS (30 min¿=¿POST-TMS).ResultsCapsaicin application resulted in substantial changes in thermal (but not mechanical) sensitivity to both heat and cold (eg. HPT PRE-CAP¿=¿43.6°C to POST-CAP¿=¿36.7°C (p¿<¿0.001)) with no differences between groups pre-rTMS. POST-TMS HPT showed no changes for any of the treatment groups, however the pain scores for the hyperalgesia curve were significantly lower for M1 vs OCC (¿24.7%, p¿<¿0.001) and for M1 vs DLFPC (¿18.3%, p¿<¿0.02).ConclusionrTMS over the primary motor cortex results in a significant analgesic effect compared to other cortical areas.