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Therefore, it is crucial to understand sex\u2010 and androgen\u2010dependent characteristics of pain\u2010related myeloid cells in mice with nerve injury\u2010induced neuropathic pain. To deplete microglia and macrophages, pexidartinib (PLX3397), an inhibitor of the colony\u2010stimulating factor 1 receptor, was orally administered, and mice were subjected to partial sciatic nerve ligation (PSL). Following PSL induction, healthy male and female mice and male gonadectomized (GDX) mice exhibited similar levels of spinal microglial activation, peripheral macrophage accumulation, and mechanical allodynia. Treatment with PLX3397 significantly suppressed mechanical allodynia in normal males; this was not observed in female and GDX male mice. Sex\u2010 and androgen\u2010dependent differences in the PLX3397\u2010mediated preventive effects were observed on spinal microglia and dorsal root ganglia (DRG) macrophages, as well as in expression patterns of pain\u2010related inflammatory mediators in these cells. Conversely, no sex\u2010 or androgen\u2010dependent differences were detected in sciatic nerve macrophages, and inhibition of peripheral CC\u2010chemokine receptor 5 prevented neuropathic pain in both sexes. Collectively, these findings demonstrate the presence of considerable sex\u2010 and androgen\u2010dependent differences in the etiology of neuropathic pain in spinal microglia and DRG macrophages but not in sciatic nerve macrophages. Given that the mechanisms of neuropathic pain may differ among experimental models and clinical conditions, accumulating several lines of evidence is crucial to comprehensively clarifying the sex\u2010dependent regulatory mechanisms of pain.<\/jats:p>","DOI":"10.1002\/glia.24535","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T05:49:38Z","timestamp":1712641778000},"page":"1402-1417","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Sexually dimorphic effects of pexidartinib on nerve injury\u2010induced neuropathic pain in mice"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1766-1584","authenticated-orcid":false,"given":"Fumihiro","family":"Saika","sequence":"first","affiliation":[{"name":"Department of Physiological Sciences School of Pharmaceutical Sciences, Wakayama Medical University  Wakayama Japan"},{"name":"Faculty of Wakayama Health 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