{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T09:06:57Z","timestamp":1789117617552,"version":"build-2803163510"},"reference-count":19,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK142785"],"award-info":[{"award-number":["R01 DK142785"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>Neurotrophin-3 (NT3), one member of the nerve growth factor family of neurotrophins, is initially synthesized as a large precursor, termed proneurotrophin-3 (proNT3), which undergoes proteolytic cleavage to generate mature NT3. A growing body of evidence suggests that proNT3 and its mature form, NT3, have opposing roles in the nervous system. A systematic literature search of PubMed was conducted using predefined search terms related to NT3, proNT3, expression, dorsal root ganglion (DRG), and pain. The role of NT3 in neuropathic pain has been debated in earlier studies. Importantly, more recent studies have shown that proNT3, rather than NT3, is expressed in the DRG. In this review, we delineate the expression and distribution pattern of proNT3 in primary sensory neurons of the DRG under normal conditions, as well as its upregulation in injured DRG following peripheral nerve injury. We highlight that DRG proNT3 upregulation is required for the development and maintenance of neuropathic pain and discuss the role of C-C chemokine ligand 2 in mediating the contribution of proNT3-triggered TrkC activation to neuropathic pain in the DRG.<\/jats:p>","DOI":"10.1177\/17448069261460645","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T04:00:26Z","timestamp":1780718426000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Precursor signaling redefined: Proneurotrophin-3, not neurotrophin-3, in primary sensory neurons as an instigator in neuropathic pain"],"prefix":"10.1177","volume":"22","author":[{"given":"Huijie","family":"Shang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruhika","family":"Iyer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1777-3272","authenticated-orcid":false,"given":"Yuan-Xiang","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA"},{"name":"Department of Physiology, Pharmacology &amp; Neuroscience, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA"},{"name":"Department of Cell Biology &amp; Molecular Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.55782\/ane-2010-1816"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20768"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/1073858417697037"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80367-0"},{"issue":"1","key":"e_1_3_2_6_2","first-page":"29","article-title":"Activation of neurotrophins in lumbar dorsal root probably contributes to neuropathic pain after spinal nerve ligation","volume":"20","author":"Kazemi A","year":"2017","unstructured":"Kazemi A, Rahmati M, Eslami R, Sheibani V. Activation of neurotrophins in lumbar dorsal root probably contributes to neuropathic pain after spinal nerve ligation. Iran J Basic Med Sci 2017; 20(1): 29\u201335.","journal-title":"Iran J Basic Med Sci"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9398-6"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1227\/NEU.0b013e318208f9c4"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2000.7432"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2007.06.027"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02940-1"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00884.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00034-7"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3909-04.2005"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)91556-3"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-21-08459.1997"},{"issue":"24","key":"e_1_3_2_17_2","first-page":"6141","article-title":"Proneurotrophin-3 contributes to chemotherapy-induced neuropathic pain through TrkC-mediated CCL2 elevation in DRG neurons","volume":"26","author":"Sharma D","year":"2025","unstructured":"Sharma D, Feng X, Wang B, Shang H, Yasin B, Bekker A, Hu H, Tao YX. Proneurotrophin-3 contributes to chemotherapy-induced neuropathic pain through TrkC-mediated CCL2 elevation in DRG neurons. EMBO Rep 2025; 26(24): 6141\u20136158.","journal-title":"EMBO Rep"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2026.106256"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules200610657"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107581"}],"container-title":["Molecular Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17448069261460645","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17448069261460645","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17448069261460645","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:17:44Z","timestamp":1789114664000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17448069261460645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":19,"alternative-id":["10.1177\/17448069261460645"],"URL":"https:\/\/doi.org\/10.1177\/17448069261460645","relation":{},"ISSN":["1744-8069","1744-8069"],"issn-type":[{"value":"1744-8069","type":"print"},{"value":"1744-8069","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"article-number":"17448069261460645"}}