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The cannabinoid type\u20101 receptor (CB\n                    <jats:sub>1<\/jats:sub>\n                    R) expressed on primary sensory neurons represents an attractive peripheral target, yet its specific role and mechanism in postoperative pain remain poorly defined. Here, by constructing a mouse model of plantar incision and combining with nociceptor\u2010selective\n                    <jats:italic>Cnr1<\/jats:italic>\n                    knockout and site\u2010specific pharmacology, we revealed that activation of CB\n                    <jats:sub>1<\/jats:sub>\n                    R in primary sensory neurons robustly alleviates postoperative mechanical allodynia. Peripheral CB\n                    <jats:sub>1<\/jats:sub>\n                    R co\u2010localizes and physically associates with the proton\u2010sensing ion channel ASIC3 in CGRP\n                    <jats:sup>+<\/jats:sup>\n                    peptidergic nociceptors in the dorsal root ganglion (DRG). The activation of CB\n                    <jats:sub>1<\/jats:sub>\n                    R signaling suppresses ASIC3\u2010mediated inward currents and subsequent calcium transients, thereby reducing neuronal excitability and ERK\n                    <jats:sub>1\/2<\/jats:sub>\n                    phosphorylation in nociceptors. Consequently, targeted activation of CB\n                    <jats:sub>1<\/jats:sub>\n                    R or blockade of ASIC3 signaling significantly alleviated postoperative pain hypersensitivity and promoted pain resolution. This study elucidated a novel peripheral mechanism by which CB\n                    <jats:sub>1<\/jats:sub>\n                    R\u2010ASIC3 physical and functional coupling in peptidergic nociceptors drives the resolution of incisional pain and provided a theoretical basis for the development of peripherally acting, non\u2010opioid analgesic strategies.\n                  <\/jats:p>","DOI":"10.1002\/advs.77925","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cannabinoid CB1 Receptor in Nociceptors Mediates Postoperative Analgesia via ASIC3 Inhibition"],"prefix":"10.1002","author":[{"given":"Kangtai","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The Second Clinical Medical College Shenzhen People's Hospital Jinan University  Shenzhen Guangdong 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