{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:33:40Z","timestamp":1785800020736,"version":"3.56.0"},"reference-count":61,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"935","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371229"],"award-info":[{"award-number":["82371229"]}],"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":["82200817"],"award-info":[{"award-number":["82200817"]}],"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":["31970938"],"award-info":[{"award-number":["31970938"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Signal."],"published-print":{"date-parts":[[2026,4,28]]},"abstract":"<jats:p>\n                    Neuropathic pain is a debilitating condition that lacks effective treatments. Corticotropin-releasing hormone (CRH) is associated with the central neural circuits involved in stress and pain. Here, we identified a peripheral CRH\u2013mediated signaling axis in dorsal root ganglion (DRG) and spinal neurons underlying neuropathic pain. Spared nerve injury (SNI) in male mice increased the abundance of CRH in small- and medium-diameter DRG neurons, specifically in their central terminals in the spinal dorsal horn. DRG-specific knockdown of CRH alleviated neuropathic pain. SNI increased\n                    <jats:italic toggle=\"yes\">Crh<\/jats:italic>\n                    expression by inducing the binding of the transcription factor SMAD1 to the\n                    <jats:italic toggle=\"yes\">Crh<\/jats:italic>\n                    promoter. Silencing SMAD1 in the DRG reduced neuropathic pain symptoms, which was accompanied by a decrease in the amount of CRH in the DRG tissue. Pharmacological antagonism of CRH receptor 2 (CRHR2), but not of CRHR1, attenuated neuropathic pain and suppressed the activation of spinal neurons and glia. Spinal CRHR2 predominantly localized to excitatory neurons and somatostatin-positive interneurons in the superficial dorsal horn. These findings reveal a SMAD1-CRH-CRHR2 axis in DRG-to-spine signaling that promotes neuropathic pain and suggest that CRHR2 antagonists be explored for its management.\n                  <\/jats:p>","DOI":"10.1126\/scisignal.aeb3953","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:58:31Z","timestamp":1777399111000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["SMAD1-mediated induction of peripheral CRH after nerve injury promotes neuropathic pain by activating spinal CRHR2"],"prefix":"10.1126","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9251-4871","authenticated-orcid":true,"given":"Cheng","family":"He","sequence":"first","affiliation":[{"name":"Department of Human Anatomy, Medical School of Nantong University, Nantong, Jiangsu 226001, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0664-6163","authenticated-orcid":true,"given":"Ling-Jie","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Pain Medicine and Special Environmental Medicine, Co-innovation Center of Neuroregeneration, Department of Pain Management of the Affiliated Hospital, Nantong University, Nantong, Jiangsu 226019, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5577-530X","authenticated-orcid":true,"given":"Yuan-Yuan","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Medical School of Nantong University, Nantong, Jiangsu 226001, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Medical School of Nantong University, Nantong, Jiangsu 226001, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Medical School of Nantong University, Nantong, Jiangsu 226001, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Medical School of Nantong University, Nantong, Jiangsu 226001, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Liang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sixth Affiliated Hospital of Nantong University, Yancheng Third People\u2019s Hospital, Yancheng, Jiangsu 224008, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Medical School of Nantong University, Nantong, Jiangsu 226001, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7432-7458","authenticated-orcid":true,"given":"Yong-Jing","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Pain Medicine and Special Environmental Medicine, Co-innovation Center of Neuroregeneration, Department of Pain Management of the Affiliated Hospital, Nantong University, Nantong, Jiangsu 226019, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6996-8683","authenticated-orcid":true,"given":"Zhi-Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Medical School of Nantong University, Nantong, Jiangsu 226001, China."},{"name":"Jiangsu Province Key Laboratory in University for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu 226001, China."},{"name":"Department of Rehabilitation Medicine, Affiliated Hospital of Nantong 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