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Recent studies have suggested a sexually dimorphic role of microglia in the maintenance of neuropathic pain in rodents. Here, we utilized RNA sequencing analysis and in vitro primary cultures of microglia to identify whether there is a common neuropathic microglial signature and characterize the sex differences in microglia in pain\u2010related regions in nerve injury and chemotherapy\u2010induced peripheral neuropathy mouse models. While mechanical allodynia and behavioral changes were observed in all models, transcriptomic analysis of microglia revealed no common transcriptional changes in spinal and supraspinal regions and in the different neuropathic models. However, there was a substantial change in microglial gene expression within the ipsilateral lumbar spinal cord 7\u2009days after chronic constriction injury (CCI) of the sciatic nerve. Both sexes upregulated genes associated with inflammation, phagosome, and lysosome activation, though males revealed a prominent global transcriptional shift not observed in female mice. Transcriptomic comparison between male spinal microglia after CCI and data from other nerve injury models and neurodegenerative microglia demonstrated a unique CCI\u2010induced signature reflecting acute activation of microglia. Further, in vitro studies revealed that only male microglia from nerve\u2010injured mice developed a reactive phenotype with increased phagocytotic activity. This study demonstrates a lack of a common neuropathic microglial signature and indicates distinct sex differences in spinal microglia, suggesting they contribute to the sex\u2010specific pain processing following nerve injury.<\/jats:p>","DOI":"10.1002\/glia.24133","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T11:01:23Z","timestamp":1642676483000},"page":"675-696","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Sex\u2010specific transcriptome of spinal microglia in neuropathic pain due to peripheral nerve injury"],"prefix":"10.1002","volume":"70","author":[{"given":"Nathan T.","family":"Fiore","sequence":"first","affiliation":[{"name":"Translational Neuroscience Facility, Department of Physiology School of Medical Sciences, University of New South Wales  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoran","family":"Yin","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Department of Neurology Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilansu","family":"Guneykaya","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Department of Neurology Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian D.","family":"Gauthier","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Department of Neurology Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica P.","family":"Hayes","sequence":"additional","affiliation":[{"name":"Translational Neuroscience Facility, Department of Physiology School of Medical Sciences, University of New South Wales  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"D'Hary","sequence":"additional","affiliation":[{"name":"Translational Neuroscience Facility, Department of Physiology School of Medical Sciences, University of New South Wales  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Butovsky","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Department of Neurology Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Evergrande Center for Immunologic Diseases Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3828-9527","authenticated-orcid":false,"given":"Gila","family":"Moalem\u2010Taylor","sequence":"additional","affiliation":[{"name":"Translational Neuroscience Facility, Department of Physiology School of Medical Sciences, University of New South Wales  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cophys.2019.03.008"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2010.08.013"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00213"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-10-29"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","unstructured":"Blackbeard J. 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