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Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia.
- Source :
- Brain: A Journal of Neurology; Sep2024, Vol. 147 Issue 9, p3157-3170, 14p
- Publication Year :
- 2024
-
Abstract
- Vincristine-induced peripheral neuropathy is a common side effect of vincristine treatment, which is accompanied by pain and can be dose-limiting. The molecular mechanisms that underlie vincristine-induced pain are not well understood. We have established an animal model to investigate pathophysiological mechanisms of vincristine-induced pain. Our previous studies have shown that the tetrodotoxin-sensitive voltage-gated sodium channel Na<subscript>v</subscript>1.6 in medium-diameter dorsal root ganglion (DRG) neurons contributes to the maintenance of vincristine-induced allodynia. In this study, we investigated the effects of vincristine administration on excitability in small-diameter DRG neurons and whether the tetrodotoxin-resistant (TTX-R) Na<subscript>v</subscript>1.8 channels contribute to mechanical allodynia. Current-clamp recordings demonstrated that small DRG neurons become hyper-excitable following vincristine treatment, with both reduced current threshold and increased firing frequency. Using voltage-clamp recordings in small DRG neurons, we now show an increase in TTX-R current density and a −7.3 mV hyperpolarizing shift in the half-maximal potential (V<subscript>1/2</subscript>) of activation of Na<subscript>v</subscript>1.8 channels in vincristine-treated animals, which likely contributes to the hyperexcitability that we observed in these neurons. Notably, vincristine treatment did not enhance excitability of small DRG neurons from Na<subscript>v</subscript>1.8 knockout mice, and the development of mechanical allodynia was delayed but not abrogated in these mice. Together, our data suggest that sodium channel Na<subscript>v</subscript>1.8 in small DRG neurons contributes to the development of vincristine-induced mechanical allodynia. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00068950
- Volume :
- 147
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Brain: A Journal of Neurology
- Publication Type :
- Academic Journal
- Accession number :
- 179512126
- Full Text :
- https://doi.org/10.1093/brain/awae071