{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:00:05Z","timestamp":1790442005315,"version":"4.1.0"},"reference-count":61,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Natural Science Foundation of Guangdong Province of China","award":["2022A1515012198"],"award-info":[{"award-number":["2022A1515012198"]}]},{"name":"Natural Science Foundation of Guangdong Province of China","award":["2024A1515012479"],"award-info":[{"award-number":["2024A1515012479"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801111"],"award-info":[{"award-number":["81801111"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870873"],"award-info":[{"award-number":["81870873"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371236"],"award-info":[{"award-number":["82371236"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Science and Technology Program","award":["JCYJ20250604174812016"],"award-info":[{"award-number":["JCYJ20250604174812016"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Paclitaxel (PTX), a widely administered chemotherapeutic drug, is known to cause neuropathic pain as a severe adverse effect. Elevated calpain expression in tumor tissues not only mediates chemoresistance but may also participate in the paclitaxel-induced neuropathic pain (PINP). There is still controversy over whether Calpain-1 (CAPN1), a subtype of calpain protease, exerts neuroprotective effects or nociceptive effects. The role and underlying mechanism of calpain1 in PINP remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>To clarify the contribution of calpain to CIPN, we examined the protein expressions of CAPN1, CAPN2, Neuronal Calcium Sensor-1(NCS-1), and Transient Receptor Potential Vanilloid 4 (TRPV4) in the DRGs and spinal dorsal horn (SDH) of PTX-treated rats. Results showed no significant changes in CAPN1 and CAPN2 protein levels in the DRGs, but marked upregulation in the SDH, along with heightened calpain activity, as evidenced by the accumulation of spectrin degradation products (a known substrate of calpain). The abnormal enhancement of CAPN1 in PTX-treated rats, contrasting with its reduced expression in most chronic pain models, prompted further investigation into its potential involvement in chronic pain. Immunofluorescence double-staining confirmed that CAPN1 localization was predominantly neuronal. Intraspinal CAPN1 overexpression restricted to CaMKII neurons in the naive rats effectively reproduced paclitaxel-induced neuropathic pain (PINP) with a comparable extent and duration of pain threshold reduction. Western blot analysis revealed that CAPN1 overexpression in spinal CaMKII neurons elevated NCS-1 expression, a calcium-binding protein essential for maintaining calcium homeostasis, which in turn strengthen the expression of CAPN2 as well as the calpain enzymatic activity. These data indicate that CAPN1 does not confer neuroprotective effects in paclitaxel-induced pain models. Rather, its overexpression in spinal CaMKII neurons directly promotes nociceptive signaling, most likely through disruption of plasma membrane calcium dynamics. Collectively, the results identify CAPN1 as a candidate therapeutic target for the clinical treatment and prevention of PINP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17448069251413873","type":"journal-article","created":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T11:22:24Z","timestamp":1767439344000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Spinal overexpression of CAPN1 in CaMKII neurons mediates paclitaxel-induced neuropathic pain via NCS-1-TRPV4 signaling"],"prefix":"10.1177","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5753-3835","authenticated-orcid":false,"given":"Ya-Ning","family":"Zhang","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Brain Function and Disease, Department of Physiology, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, Guangdong, P. R. China"},{"name":"Pain Research Center, Zhongshan Medical School of Sun Yat-Sen University, Guangzhou, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7128-4501","authenticated-orcid":false,"given":"Shao-Xia","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7771-2399","authenticated-orcid":false,"given":"Qiao-Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Brain Function and Disease, Department of Physiology, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0501-8715","authenticated-orcid":false,"given":"Jia-Qi","family":"You","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Brain Function and Disease, Department of Physiology, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, Guangdong, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3667-9595","authenticated-orcid":false,"given":"Yao-Hui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Brain Function and Disease, Department of Physiology, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, Guangdong, P. R. 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