{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T16:01:25Z","timestamp":1777564885278,"version":"3.51.4"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,26]],"date-time":"2025-01-26T00:00:00Z","timestamp":1737849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>In this study, we investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied over the left upper limb primary motor cortex (M1) on the offset analgesia (OA) phenomenon, a measure of endogenous pain modulation. In particular, we aim to determine whether rTMS influences OA differently in the forearm region, corresponding to the stimulated cortical area, compared to the trigeminal region. Twenty-two healthy volunteers underwent three experimental sessions: a baseline session without stimulation, an active rTMS session, and a sham rTMS session. Quantitative sensory testing (QST) paradigms, including warm and cold detection thresholds, heat pain threshold corresponding to a visual analogue scale (VAS) score of approximately 50\u201360 out of 100 (Pain50\u201360), and constant and offset trials, were assessed in both the forearm and trigeminal regions. The results revealed that active rTMS significantly enhanced the OA phenomenon in the forearm during the late phase, while no significant effects were observed in the trigeminal region. These findings suggest that rTMS may modulate central pain mechanisms in a body region-specific manner, potentially linked to the somatotopic organization of M1. This study points to possible mechanisms of action of rTMS for pain relief, highlighting the importance of region-specific effects in chronic pain treatment. Further research is needed to investigate the underlying mechanisms and clinical applicability of rTMS in patients with chronic pain conditions, especially when OA is compromised.<\/jats:p>","DOI":"10.3390\/life15020182","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T04:59:10Z","timestamp":1737953950000},"page":"182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of Repetitive Transcranial Magnetic Stimulation Applied over the Primary Motor Cortex on the Offset Analgesia Phenomenon"],"prefix":"10.3390","volume":"15","author":[{"given":"Elisa","family":"Antoniazzi","sequence":"first","affiliation":[{"name":"Translational Neurophysiology Research Section, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camilla","family":"Cavigioli","sequence":"additional","affiliation":[{"name":"Translational Neurophysiology Research Section, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Tang","sequence":"additional","affiliation":[{"name":"Translational Neurophysiology Research Section, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Zoccola","sequence":"additional","affiliation":[{"name":"Translational Neurophysiology Research Section, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6527-3558","authenticated-orcid":false,"given":"Massimiliano","family":"Todisco","sequence":"additional","affiliation":[{"name":"Translational Neurophysiology Research Section, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1513-2113","authenticated-orcid":false,"given":"Cristina","family":"Tassorelli","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Headache Science and Neurorehabilitation Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0309-6410","authenticated-orcid":false,"given":"Giuseppe","family":"Cosentino","sequence":"additional","affiliation":[{"name":"Translational Neurophysiology Research Section, IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/SPC.0000000000000055","article-title":"Descending pain modulation and chronification of pain","volume":"8","author":"Ossipov","year":"2014","journal-title":"Curr. 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