{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:37:07Z","timestamp":1791927427545,"version":"4.3.4"},"posted":{"date-parts":[[2026,9,22]]},"group-title":"Neurology","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01AT009491"],"award-info":[{"award-number":["R01AT009491"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2017\/12943-8"],"award-info":[{"award-number":["2017\/12943-8"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>The primary motor cortex is a critical hub for pain control, yet its few identified regulatory mechanisms \u2014 intracortical inhibition and oscillatory markers \u2014 predict symptoms inconsistently. The prevailing view holds that pain results from reduced inhibition, a fixed deficit, rather than from resistance to inhibition that rehabilitation can reverse. Here we show that motor cortex pain compensation is instead a modifiable state whose analgesic efficiency depends on allostatic load. In a fibromyalgia trial and a knee osteoarthritis cohort assessed with parallel EEG and transcranial magnetic stimulation, a signature combining central theta asymmetry and intracortical inhibition was unrelated or inversely related to symptom burden under low allostatic load but positively related to it under high load in fibromyalgia, and its protective association was attenuated under high load in osteoarthritis \u2014 the same signal carrying different clinical meaning. A burden-adjusted index modelled on the homeostatic model assessment of insulin resistance was elevated under high load, predicted improvement after rehabilitation beyond baseline severity, and fell in responders but not in non-responders; in both cohorts the neurophysiological component itself recalibrated with response. Motor cortex compensation is thus degraded by allostatic load and restored by rehabilitation.<\/jats:p>","DOI":"10.64898\/2026.09.21.26363555","type":"posted-content","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:50:11Z","timestamp":1790124611000},"source":"Crossref","is-referenced-by-count":1,"title":["Motor cortex pain compensation is modifiable: allostatic load degrades its analgesic efficiency and rehabilitation restores it"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1307-9355","authenticated-orcid":false,"given":"Felipe","family":"Fregni","sequence":"first","affiliation":[{"name":"Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Imamura","sequence":"additional","affiliation":[{"name":"Instituto de Medicina F\u00edsica e Reabilita\u00e7\u00e3o do Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo (IMREA HCFMUSP), S\u00e3o Paulo, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Camargo","sequence":"additional","affiliation":[{"name":"Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Pacheco-Barrios","sequence":"additional","affiliation":[{"name":"Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Unidad de Investigaci\u00f3n para la Generaci\u00f3n y S\u00edntesis de Evidencias en Salud, Vicerrectorado de Investigaci\u00f3n, Universidad San Ignacio de Loyola, Lima 15023, Peru."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Carolyna","family":"Lepesteur Gianloren\u00e7o","sequence":"additional","affiliation":[{"name":"Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linamara","family":"Battistella","sequence":"additional","affiliation":[{"name":"Instituto de Medicina F\u00edsica e Reabilita\u00e7\u00e3o do Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo (IMREA 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