{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:20:15Z","timestamp":1788470415446,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,1]]},"group-title":"Neuroscience","reference-count":71,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["NS130046"],"award-info":[{"award-number":["NS130046"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DK128475"],"award-info":[{"award-number":["DK128475"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Descending projections from the brain to the spinal cord can regulate painful stimulus processing and are modulated by endogenous and exogenous opioids. We investigated the role of mu opioid receptors (MORs) in GABAergic vs. glutamatergic neurons of the rostral ventral medulla (RVM) in a mouse model of chronic neuropathic pain. We found that activating glutamatergic and GABAergic neurons in the RVM both result in antinociception at baseline, but glutamatergic neurons\n                  <jats:italic>enhance<\/jats:italic>\n                  pain responses after nerve injury. We then interrogated the role of RVM MOR signaling on neuropathic pain by using CRISPR\/Cas9 to delete MOR in glutamatergic or GABAergic RVM neurons. We found that MOR knockout in glutamatergic and GABAergic RVM neurons precipitates early neuropathic pain onset with no effect on chronic pain intensity. These results suggest that RVM MOR signaling modulates hypersensitivity in the early phase of injury, but chronic neuropathic pain is largely independent of mu opioid receptor signaling.\n                <\/jats:p>","DOI":"10.64898\/2026.08.26.747135","type":"posted-content","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:20:21Z","timestamp":1788304821000},"source":"Crossref","is-referenced-by-count":0,"title":["The role of mu opioid receptors on excitatory and inhibitory neurons in the rostral ventromedial medulla in neuropathic pain"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7521-7218","authenticated-orcid":false,"given":"Jamie C.","family":"Moffa","sequence":"first","affiliation":[{"name":"WashU Medicine Pain Center, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110"},{"name":"Washington University Medical Scientist Training Program, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Gao","sequence":"additional","affiliation":[{"name":"WashU Medicine Pain Center, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vani","family":"Kalyanaraman","sequence":"additional","affiliation":[{"name":"WashU Medicine Pain Center, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Heitmeier","sequence":"additional","affiliation":[{"name":"WashU Medicine Pain Center, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3732-890X","authenticated-orcid":false,"given":"Bryan","family":"Copits","sequence":"additional","affiliation":[{"name":"WashU Medicine Pain Center, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026090313401150000_2026.08.26.747135v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(78)90093-X"},{"key":"2026090313401150000_2026.08.26.747135v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(77)90487-5"},{"key":"2026090313401150000_2026.08.26.747135v1.3","doi-asserted-by":"crossref","unstructured":"Andrew H Cooper , Naomi S Hedden , Pranav Prasoon , Yanmei Qi , Taylor BK , Griggs RB . Post-surgical latent pain sensitization is driven by descending serotonergic facilitation and masked by \u00b5-opioid receptor constitutive activity (MORCA) in the rostral ventromedial medulla. 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H. Moreira de Souza , Robson Lilo Vizin , Xu Yue , Richard D. Palmiter , E. Navratilova , Frank Porreca . Descending facilitation from rostral ventromedial medulla mu opioid receptor-expressing neurons is necessary for maintenance of sensory and affective dimensions of chronic neuropathic pain. 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Godin , Herry C , Cyril Herry , Xavier Fioramonti , Xavier Fioramonti , Landry M , Marc Landry , De Koninck Y , Yves De Koninck , Fossat P , Pascal Fossat . Switch of serotonergic descending inhibition into facilitation by a spinal chloride imbalance in neuropathic pain. 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