Proneurotrophin-3 contributes to chemotherapy-induced neuropathic pain through TrkC-mediated CCL2 elevation in DRG neurons.

ABSTRACT: Cancer patients undergoing treatment with antineoplastic drugs often experience chemotherapy-induced neuropathic pain (CINP), and therapeutic options for managing CINP are limited. Here, we show that systemic paclitaxel administration upregulates the expression of neurotrophin-3 (Nt3) 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

SUBMITTER: Sharma D 

PROVIDER: S-EPMC12714783 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature