Effects of vincristine on the properties of low threshold mechanoreceptors and high threshold mechanoreceptors in the hindpaw glabrous skin of mice.

Abstract

Vincristine is an important chemotherapy drug to treat various types of cancer, but it induces peripheral neuropathy, leading to numbness and mechanical allodynia in the hands and feet of patients. The peripheral neuropathy is a dose-limiting toxicity of vincristine chemotherapy. How vincristine treatment causes numbness and mechanical allodynia remains incompletely understood. In the present study, we utilized Nav1.8-ChR2 transgenic mice in which Nav1.8-ChR2-positive and Nav1.8-ChR2-negative mechanoreceptors could be characterized using the opto-electrophysiological method. Nav1.8-ChR2-negative Aβ- and Aδ-fiber mechanoreceptors are primarily low-threshold mechanoreceptors (LTMRs). On the other hand, Nav1.8-ChR2-positive Aβ- and Aδ-fiber mechanoreceptors are mainly high-threshold mechanoreceptors (HTMRs). We have shown that the mechanical threshold of Nav1.8-ChR2-negative Aβ-fiber mechanoreceptors, but not Nav1.8-ChR2-negative Aδ-fiber mechanoreceptors, were increased significantly in the animals treated with vincristine. In contrast, the mechanical threshold of Nav1.8-ChR2-positive Aβ-fiber mechanoreceptors were significantly reduced following vincristine treatment. Vincristine treatment did not significantly affect the mechanical sensitivity of Nav1.8-ChR2-positive Aδ- and C-fiber mechanoreceptors. Vincristine treatment also did not affect the opto-sensitivity of Nav1.8-ChR2-positive Aβ-, Aδ-, and C-fiber mechanoreceptors. Our findings suggest that mechanical sensitivity is decreased in Aβ-fiber LTMRs and increased in Aβ-HTMRs following vincristine treatment, providing insights into vincristine-induced numbness and mechanical allodynia.