{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:48:47Z","timestamp":1788922127747,"version":"build-2803163510"},"reference-count":43,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100017684","name":"Foundation Research Project of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20241766"],"award-info":[{"award-number":["BK20241766"]}],"id":[{"id":"10.13039\/501100017684","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Research Fund of Higher Education Institutions in Jiangsu Province","award":["22KJA320007"],"award-info":[{"award-number":["22KJA320007"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301414"],"award-info":[{"award-number":["82301414"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>The precise mechanisms underlying the pathogenesis of opioid-induced thermal hyperalgesia and tolerance are not yet fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In adult CD-1 mice, repeated morphine treatment was used to examine the expression of the non-canonical pathway of sonic hedgehog signaling, behavioral changes, and neurochemical alterations induced by morphine in the spinal cord and DRG. Additionally, to delve into the underlying mechanisms of the non-canonical pathway of Shh signaling in morphine-induced thermal hyperalgesia (MITH) and tolerance, we utilize the brain-derived neurotrophic factor (BDNF) inhibitor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Morphine administration repeatedly resulted in apparent thermal hyperalgesia and tolerance. The initiation and maintenance of MITH and tolerance, as well as related neurochemical alterations, were greatly inhibited by pharmacological and genetic suppression of the mTOR. By blocking the mTOR\/p70 ribosomal S6 protein kinase 1 (S6K1)\/Gli1 signaling, the morphine-induced increase in BDNF was considerably inhibited. Moreover, mTOR activator injection in naive mice resulted in significant heat hyperalgesia and BDNF upregulation. Suppression of BDNF effectively mitigated the development of thermal hyperalgesia induced by the mTOR activator.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>These findings indicate that the non-canonical pathway of Shh signaling might serve as a crucial mediator in the development of MITH and tolerance through the regulation of BDNF expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17448069251376198","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T11:07:39Z","timestamp":1756206459000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of mTOR\/S6K1\/Gli1 signaling alleviates morphine-induced thermal hyperalgesia and tolerance"],"prefix":"10.1177","volume":"21","author":[{"given":"Xing-He","family":"Wang","sequence":"first","affiliation":[{"name":"Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Jiangsu, China"},{"name":"Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Xuzhou Central Hospital, Xuzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Xuzhou New Health Hospital, Xuzhou, 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