{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T18:43:49Z","timestamp":1772995429525,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["24ZR1414100"],"award-info":[{"award-number":["24ZR1414100"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC3500703"],"award-info":[{"award-number":["2022YFC3500703"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chemotherapy\u2010induced peripheral neuropathy (CIPN), characterised by a stocking\u2010glove distribution of numbness and pain, is a severe clinical challenge. Our previous study showed that overexpression of neuronal G protein\u2010coupled receptor kinase (GRK2) in the spinal dorsal horn (SDH) prevented cisplatin\u2010induced CIPN in mice. The underlying mechanism, however, remains unclear. This study aimed to explore the role of insulin\u2010like growth factor 1 (IGF1) in preventing CIPN through neuronal GRK2 in the SDH of mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CIPN model was established by intraperitoneally injecting cisplatin (23\u2009mg\/kg) in mice. Neuronal IGF1R or GRK2 in SDH was downregulated by intraspinally injecting an AAV vector delivering IGF1R or GRK2 shRNA with hSyn promoter. Mechanical allodynia and sensory deficits were assessed by von Frey test and adhesive removal test. The expression of IGF1, IGF1R and Iba1 was assessed by immunostaining. Neuroinflammation was assessed by real\u2010time PCR. The IGF1R and GRK2 levels were assessed by Western blot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cisplatin chemotherapy induced a decrease of IGF1 and p\u2010IGF1R in SDH; intrathecal (i.t) injection of recombinant IGF1 (rIGF1) significantly prevented cisplatin\u2010induced mechanical allodynia, sensory deficit, and microglia activation and neuroinflammation in SDH. IGF1R was primarily localised within neurons (~81%). Downregulation of neuronal IGF1R (AAV\u2010shIGF1R) inhibited the preventive effect of i.t. rIGF1 on CIPN, and on the upregulation of GRK2 in SDH. Furthermore, downregulation of neuronal GRK2 in SDH inhibited the preventive effect of i.t. rIGF1 on CIPN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>I.t. injection of rIGF1 regulates neuronal GRK2 through neuronal IGF1R in SDH, alleviates microglial activation and neuroinflammation, thereby preventing cisplatin\u2010induced CIPN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>This work elucidates the role of neuronal IGF1\/IGF1R in the process of CIPN prevention and provides new animal\u2010based evidence for CIPN prevention by targeting neuronal IGF1\/IGF1R in SDH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejp.70161","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T10:15:48Z","timestamp":1761905748000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting Upregulation of Neuronal\n                    <scp>IGF1<\/scp>\n                    \/\n                    <scp>IGF1R<\/scp>\n                    Signalling in the Spinal Cord Prevents Cisplatin\u2010Induced Peripheral Neuropathy in Mice"],"prefix":"10.1002","volume":"29","author":[{"given":"Chieh\u2010Ru","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, Institute of Acupuncture Research, Institutes of Integrative Medicine, Shanghai Medical College Fudan University  Shanghai People's Republic of 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