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We aimed to evaluate the mechanism of this synergistic effect of the concomitant administration for neuropathic pain using chronic constriction injury model rats. Fifty male Wister rats of 7\u2010week\u2010old were used. Right sciatic nerve ligation was performed in 40 rats and they were sub\u2010divided into four groups: vehicle, mirogabalin, diclofenac sodium and co\u2010administration of them. Ten rats underwent sham surgery. Fluorogold was attached to sciatic nerve during surgery. Von Frey filament and weight bearing tests were performed on postoperative Day 6 as behavioral assessments and drug was administrated intraperitoneally. Half rats in each group underwent behavioral assessment and perfusion fixation using 4% paraformaldehyde on postoperative Day 7 and remaining on postoperative Day 14. Subsequently, dorsal root ganglion at L4 to L6 was collected and examined immunohistochemistry for calcitonin gene\u2010related peptide, and their immunoreactivity in fluorogold\u2010labeled neurons was measured. Spinal cord at lumbar swelling was resected, immunostained for ionized\u2010calcium\u2010binding adapter molecule\u20101 and glial fibrillary acidic protein, and immunoreactive neurons in dorsal horn of spinal cords were calculated as the occupancy of them. Mirogabalin suppresses the neuropeptide\u2010release from presynaptic afferent neuron directly and it resulted in suppressing glia cells activation. Diclofenac sodium inhibits cyclooxygenase\u20102 and prostaglandin production, related to allodynia. These effects of mirogabalin and diclofenac sodium, respectively, inhibited glia cells strongly, which is presumed to be one of the mechanisms for the effectiveness of their co\u2010administration for neuropathic pain.<\/jats:p>","DOI":"10.1002\/jor.25977","type":"journal-article","created":{"date-parts":[[2024,9,22]],"date-time":"2024-09-22T09:38:31Z","timestamp":1726997911000},"page":"200-209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Analgesic effects of co\u2010administration of mirogabalin and diclofenac sodium on neuropathic pain in rats"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7711-1202","authenticated-orcid":false,"given":"Hiroto","family":"Chikubu","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medicine Chiba University Chiba Japan"},{"name":"Department of Anesthesiology, Graduate School of Medicine Chiba 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