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Here, we show that systemic paclitaxel administration upregulates the expression of neurotrophin-3 (\n                    <jats:italic>Nt3<\/jats:italic>\n                    ) mRNA and its encoded proneurotrophin-3 (proNT3) protein in the neurons of dorsal root ganglia (DRG), but not in the spinal cord. Blocking this upregulation attenuates paclitaxel-induced mechanical, heat, and cold nociceptive hypersensitivities and spontaneous pain without altering acute pain and locomotor activity in male and female mice. Conversely, mimicking paclitaxel-induced upregulation of DRG proNT3 produces enhanced responses to mechanical, heat, and cold stimuli and spontaneous pain in naive male and female mice. Mechanistically, proNT3 triggers tropomyosin receptor kinase C (TrkC) activation and participates in the paclitaxel-induced increases of C-C chemokine ligand 2 (\n                    <jats:italic>Ccl2<\/jats:italic>\n                    ) mRNA and CCL2 protein in the DRG. Given that CCL2 is an endogenous initiator of CINP and that\n                    <jats:italic>Nt3<\/jats:italic>\n                    mRNA co-expresses with TrkC and\n                    <jats:italic>Ccl2<\/jats:italic>\n                    mRNAs in DRG neurons, proNT3 likely contributes to CINP through TrkC-mediated activation of the Ccl2 gene in DRG neurons. Thus, proNT3 may be a potential target for CINP treatment.\n                  <\/jats:p>","DOI":"10.1038\/s44319-025-00534-1","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T11:02:16Z","timestamp":1764154936000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Proneurotrophin-3 contributes to chemotherapy-induced neuropathic pain through TrkC-mediated CCL2 elevation in DRG neurons"],"prefix":"10.1038","volume":"26","author":[{"given":"Dilip","family":"Sharma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhou","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijie","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bushra","family":"Yasin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Bekker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2306-2514","authenticated-orcid":false,"given":"Huijuan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1777-3272","authenticated-orcid":false,"given":"Yuan-Xiang","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"534_CR1","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1002\/ejp.1169","volume":"22","author":"S Al-Mazidi","year":"2018","unstructured":"Al-Mazidi S, Alotaibi M, Nedjadi T, Chaudhary A, Alzoghaibi M, Djouhri L (2018) Blocking of cytokines signalling attenuates evoked and spontaneous neuropathic pain behaviours in the paclitaxel rat model of chemotherapy-induced neuropathy. 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