{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:53:42Z","timestamp":1789563222833,"version":"build-2803163510"},"reference-count":114,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordination for the Improvement of Higher Education Personnel","award":["1409259"],"award-info":[{"award-number":["1409259"]}]},{"name":"Hospital S\u00edrio-Liban\u00eas","award":["1409259"],"award-info":[{"award-number":["1409259"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epidural motor cortex stimulation (MCS) is an effective treatment for refractory neuropathic pain; however, some individuals are unresponsive. In this study, we correlated the effectiveness of MCS and refractoriness with the expression of cytokines, neurotrophins, and nociceptive mediators in the dorsal root ganglion (DRG), sciatic nerve, and plasma of rats with sciatic neuropathy. MCS inhibited hyperalgesia and allodynia in two-thirds of the animals (responsive group), and one-third did not respond (refractory group). Chronic constriction injury (CCI) increased IL-1\u03b2 in the nerve and DRG, inhibited IL-4, IL-10, and IL-17A in the nerve, decreased \u03b2-endorphin, and enhanced substance P in the plasma, compared to the control. Responsive animals showed decreased NGF and increased IL-6 in the nerve, accompanied by restoration of local IL-10 and IL-17A and systemic \u03b2-endorphin. Refractory animals showed increased TNF-\u03b1 and decreased IFN\u03b3 in the nerve, along with decreased TNF-\u03b1 and IL-17A in the DRG, maintaining low levels of systemic \u03b2-endorphin. Our findings suggest that the effectiveness of MCS depends on local control of inflammatory and neurotrophic changes, accompanied by recovery of the opioidergic system observed in neuropathic conditions. So, understanding the refractoriness to MCS may guide an improvement in the efficacy of the technique, thus benefiting patients with persistent neuropathic pain.<\/jats:p>","DOI":"10.3390\/ijms24097796","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T02:06:35Z","timestamp":1682388395000},"page":"7796","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Systemic and Peripheral Mechanisms of Cortical Stimulation-Induced Analgesia and Refractoriness in a Rat Model of Neuropathic Pain"],"prefix":"10.3390","volume":"24","author":[{"given":"Danielle V.","family":"Assis","sequence":"first","affiliation":[{"name":"Laboratory of Neuroscience, Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo 01308-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Carolina P.","family":"Campos","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroscience, Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo 01308-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda F. N.","family":"Paschoa","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroscience, Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo 01308-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talita F.","family":"Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroscience, Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo 01308-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich T.","family":"Fonoff","sequence":"additional","affiliation":[{"name":"Division of Functional Neurosurgery, Department of Neurology, University of Sao Paulo Medical School, S\u00e3o Paulo 05402-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5351-6575","authenticated-orcid":false,"given":"Rosana L.","family":"Pagano","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroscience, Hospital S\u00edrio-Liban\u00eas, S\u00e3o Paulo 01308-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1212\/01.wnl.0000282763.29778.59","article-title":"Neuropathic pain: Redefinition and a grading system for clinical and research purposes","volume":"70","author":"Treede","year":"2008","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/sc.2015.225","article-title":"Neuroplasticity of ascending and descending pathways after somatosensory system injury: Reviewing knowledge to identify neuropathic pain therapeutic targets","volume":"54","author":"Castany","year":"2016","journal-title":"Spinal Cord"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/00002508-200009001-00006","article-title":"Pain mechanisms and management: A central perspective","volume":"16","author":"Mannion","year":"2000","journal-title":"Clin. 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