Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia

• DOI: 10.1093/brain/awae071
• Publication Date: 2024-03-07T00:40:45Z
• Authors: Ana Paula Nascime...; Huiran Zhang; Lubin Chen; Philip R Effraim; Carolina Gomis-Perez; Xiaoyang Cheng; Jianying Huang; Stephen G Waxman; Sulayman D Dib-Hajj
• Keywords: Dorsal root ganglion; Allodynia

Abstract Vincristine-induced peripheral neuropathy is a common side effect of vincristine treatment, which accompanied by pain and can be dose-limiting. The molecular mechanisms that underlie vincristine-induced are not well understood. We have established an animal model to investigate pathophysiological pain. Our previous studies shown the tetrodotoxin-sensitive voltage-gated sodium channel Nav1.6 in medium-diameter dorsal root ganglion (DRG) neurons contributes maintenance allodynia. In this study, we investigated effects administration on excitability small-diameter DRG whether tetrodotoxin-resistant (TTX-R) Nav1.8 channels contribute mechanical Current-clamp recordings demonstrated small become hyper-excitable following with both reduced current threshold increased firing frequency. Using voltage-clamp neurons, now show increase TTX-R density −7.3 mV hyperpolarizing shift half-maximal potential (V1/2) activation vincristine-treated animals, likely hyperexcitability observed these neurons. Notably, treatment did enhance from knockout mice, development allodynia was delayed but abrogated mice. Together, our data suggest