Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPASSIS, Danielle V.CAMPOS, Ana Carolina P.PASCHOA, Amanda F. N.SANTOS, Talita F.FONOFF, Erich T.PAGANO, Rosana L.2023-08-162023-08-162023INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.24, n.9, article ID 7796, 18p, 20231661-6596https://observatorio.fm.usp.br/handle/OPI/54723Epidural 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 fi in the nerve and DRG, inhibited IL-4, IL-10, and IL-17A in the nerve, decreased beta-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 beta-endorphin. Refractory animals showed increased TNF- alpha and decreased IFN gamma in the nerve, along with decreased TNF- alpha and IL-17A in the DRG, maintaining low levels of systemic beta-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.engopenAccessmotor cortex stimulationneuropathic painsciatic nerveinflammationneurotrophinssubstance Pbeta-endorphinmotor cortex stimulationdorsal-root gangliachronic constriction injurysatellite glial-cellsbeta-endorphinsciatic-nervedynamic regulationsensory neuronssubstance-ptnf-alphaarticleCopyright MDPI10.3390/ijms24097796Biochemistry & Molecular BiologyChemistry, Multidisciplinary1422-0067