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However, current applications of TMS to pain have been restricted to measurements of motor evoked potentials (MEPs) from peripheral muscles. Here, TMS was combined with electroencephalography (EEG) to determine whether experimental pain could induce alterations in cortical inhibitory\/facilitatory activity observed in TMS-evoked potentials (TEPs). In Experiment 1 (n=29), multiple sustained thermal stimuli were administered to the forearm, with the first, second, and third block of thermal stimuli consisting of warm but non-painful (pre-pain block), painful (pain block) and warm but non-painful (post-pain block) temperatures, respectively. During each stimulus, TMS pulses were delivered while EEG (64 channels) was simultaneously recorded. Verbal pain ratings were collected between TMS pulses. Relative to pre-pain warm stimuli, painful stimuli led to an increase in the amplitude of the frontocentral negative peak ~45 ms post-TMS (N45), with a larger increase associated with higher pain ratings. Experiments 2 and 3 (n=10 in each) showed that the increase in the N45 in response to pain was not due to changes in sensory potentials associated with TMS, or a result of stronger reafferent muscle feedback during pain. This is the first study to use combined TMS-EEG to examine alterations in cortical excitability in response to pain. These results suggest that the N45 TEP peak, which indexes GABAergic neurotransmission, is implicated in pain perception and is a potential marker of individual differences in pain sensitivity.<\/jats:p>","DOI":"10.7554\/elife.88567","type":"journal-article","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T07:04:29Z","timestamp":1688713469000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.88567","source":"Crossref","is-referenced-by-count":3,"title":["Combined transcranial magnetic stimulation and electroencephalography reveals alterations in cortical excitability during pain"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6357-0746","authenticated-orcid":true,"given":"Nahian Shahmat","family":"Chowdhury","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g7s6g79","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Pain IMPACT, Neuroscience Research Australia","place":["Sydney, Australia"]},{"id":[{"id":"https:\/\/ror.org\/03r8z3t63","id-type":"ROR","asserted-by":"publisher"}],"name":"University of New South Wales","place":["Sydney, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9156-0534","authenticated-orcid":true,"given":"Alan KI","family":"Chiang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g7s6g79","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Pain IMPACT, Neuroscience Research Australia","place":["Sydney, Australia"]},{"id":[{"id":"https:\/\/ror.org\/03r8z3t63","id-type":"ROR","asserted-by":"publisher"}],"name":"University of New South Wales","place":["Sydney, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1409-8179","authenticated-orcid":true,"given":"Samantha K","family":"Millard","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g7s6g79","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Pain IMPACT, Neuroscience Research Australia","place":["Sydney, Australia"]},{"id":[{"id":"https:\/\/ror.org\/03r8z3t63","id-type":"ROR","asserted-by":"publisher"}],"name":"University of New South Wales","place":["Sydney, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Skippen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g7s6g79","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Pain IMPACT, Neuroscience Research Australia","place":["Sydney, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0524-4883","authenticated-orcid":true,"given":"Wei-Ju","family":"Chang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g7s6g79","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Pain IMPACT, Neuroscience Research Australia","place":["Sydney, Australia"]},{"id":[{"id":"https:\/\/ror.org\/00eae9z71","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Health Sciences, College of Health, Medicine and Wellbeing, The University of Newcastle","place":["Callaghan, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3111-3756","authenticated-orcid":true,"given":"David A","family":"Seminowicz","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g7s6g79","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Pain IMPACT, Neuroscience Research Australia","place":["Sydney, Australia"]},{"id":[{"id":"https:\/\/ror.org\/02grkyz14","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Biophysics, Schulich School of Medicine & Dentistry, University of Western Ontario","place":["London, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siobhan M","family":"Schabrun","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01g7s6g79","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Pain IMPACT, Neuroscience Research Australia","place":["Sydney, Australia"]},{"id":[{"id":"https:\/\/ror.org\/02grkyz14","id-type":"ROR","asserted-by":"publisher"}],"name":"The Gray Centre for Mobility and Activity, University of Western Ontario","place":["London, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1016\/j.jpain.2022.07.007","article-title":"To Calibrate or not to Calibrate? 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