{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:48:29Z","timestamp":1791895709853,"version":"4.3.4"},"reference-count":23,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21H03026"],"award-info":[{"award-number":["21H03026"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K16593"],"award-info":[{"award-number":["22K16593"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K16614"],"award-info":[{"award-number":["22K16614"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>Background: IL-1\u03b2 plays a critical role in the pathophysiology of neuroinflammation. The presence of cleaved IL-1\u03b2 (cIL-1\u03b2) in the neurons of the dorsal root ganglion (DRG) implicates its function in biological signaling arising from the sensory neuron. This study was conducted to analyze the role of IL-1\u03b2 in nociceptive transduction after tissue injury. Methods: A plantar incision was made in C57BL\/6 mice, following which immunohistochemistry and RNA scope in situ hybridization were performed at various time points to analyze cIL-1\u03b2, caspase-1, and IL-1 receptor 1 (IL-1R1) expression in the DRG. The effect of intrathecal administration of a caspase-1 inhibitor or regional anesthesia using local anesthetics on cIL-1\u03b2 expression and pain hypersensitivity was analyzed by immunohistochemistry and behavioral analysis. ERK phosphorylation was also analyzed to investigate the effect of IL-1\u03b2 on the activity of spinal dorsal horn neurons. Results: cIL-1\u03b2 expression was significantly increased in caspase-1-positive DRG neurons 5\u00a0min after the plantar incision. Intrathecal caspase-1 inhibitor treatment inhibited IL-1\u03b2 cleavage and pain hypersensitivity after the plantar incision. IL-1R1 was also detected in the DRG neurons, although the majority of IL-1R1-expressing neurons lacked cIL-1\u03b2 expression. Regional anesthesia using local anesthetics prevented cIL-1\u03b2 processing. Plantar incision-induced phosphorylation of ERK was inhibited by the caspase-1 inhibitor. Conclusion: IL-1\u03b2 in the DRG neuron undergoes rapid cleavage in response to tissue injury in an activity-dependent manner. Cleaved IL-1\u03b2 causes injury-induced functional activation of sensory neurons and pain hypersensitivity. IL-1\u03b2 in the primary afferent neurons is involved in physiological nociceptive signal transduction.<\/jats:p>","DOI":"10.1177\/17448069241285357","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T21:01:31Z","timestamp":1725570091000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Rapid cleavage of IL-1\u03b2 in DRG neurons produces tissue injury-induced pain hypersensitivity"],"prefix":"10.1177","volume":"20","author":[{"given":"Daisuke","family":"Fujita","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan"},{"name":"Research Unit for the Neurobiology of Pain, Kyoto Prefectural University of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Research Unit for the Neurobiology of Pain, Kyoto Prefectural University of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Yamakita","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan"},{"name":"Research Unit for the Neurobiology of Pain, Kyoto Prefectural University of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiko","family":"Horii","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan"},{"name":"Research Unit for the Neurobiology of Pain, Kyoto Prefectural University of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan"},{"name":"Research Unit for the 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