{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T06:50:48Z","timestamp":1775890248847,"version":"3.50.1"},"posted":{"date-parts":[[2025,1,27]]},"group-title":"Neuroscience","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,27]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Nerve damage induces a robust\n                  <jats:italic>de novo<\/jats:italic>\n                  expression of the pain-modulatory peptide neuropeptide Y (NPY) in large-diameter primary afferent neurons that innervate the dorsal horn of the spinal cord and the dorsal column nuclei. To determine whether this functions to modulate peripheral neuropathic pain, we selectively deleted the\n                  <jats:italic>Npy<\/jats:italic>\n                  gene in neurons of the dorsal root ganglion (DRG), without disruption of its expression in brain or dorsal horn neurons. We then subjected sensory neuron-specific NPY deletion mutant mice (\n                  <jats:italic>Pirt<\/jats:italic>\n                  -NPY) and their wild-type controls to either sham surgery, spared sural nerve injury (SNI) or spared tibial nerve injury (tSNI). Conditional\n                  <jats:italic>Npy<\/jats:italic>\n                  deletion did not change the severity or duration of static mechanical, dynamic mechanical, or cold allodynia in SNI or tSNI models, nor ongoing neuropathic pain as assessed with conditioned place preference to gabapentin. When injected after the resolution of tSNI-induced mechanical hypersensitivity (a latent pain sensitization model of chronic neuropathic pain), the NPY Y1 receptor-specific antagonist BIBO3304 equally reinstated mechanical hypersensitivity in\n                  <jats:italic>Pirt<\/jats:italic>\n                  -NPY mice and their wildtype controls. We conclude that nerve injury-induced upregulation of NPY in sensory neurons does not cause mechanical or cold hypersensitivity or ongoing pain, and that tonic inhibitory control of neuropathic pain by NPY in the spinal cord is mediated by release from dorsal horn interneurons rather than sensory neurons.\n                <\/jats:p>","DOI":"10.1101\/2025.01.25.634591","type":"posted-content","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T11:05:28Z","timestamp":1737975928000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>De novo<\/i>\n                  expression of neuropeptide Y in sensory neurons does not contribute to peripheral neuropathic pain"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4737-9364","authenticated-orcid":false,"given":"A.H.","family":"Cooper","sequence":"first","affiliation":[{"name":"Pittsburgh Center for Pain Research and Opioid Research Center, Department of Anesthesiology & Perioperative Medicine, Pittsburgh, PA, 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Nie","sequence":"additional","affiliation":[{"name":"Pittsburgh Center for Pain Research and Opioid Research Center, Department of Anesthesiology & Perioperative Medicine, Pittsburgh, PA, 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.S.","family":"Hedden","sequence":"additional","affiliation":[{"name":"Pittsburgh Center for Pain Research and Opioid Research Center, Department of Anesthesiology & Perioperative Medicine, Pittsburgh, PA, 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Herzog","sequence":"additional","affiliation":[{"name":"St Vincent\u2019s Centre for Applied Medical Research (AMR), Sydney"},{"name":"St Vincent\u2019s Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.K.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Pittsburgh Center for Pain Research and Opioid Research Center, Department of Anesthesiology & Perioperative Medicine, Pittsburgh, PA, 15213, 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