Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, United States; Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, Japan.
Department of Orthopaedic Surgery, Wakayama Medical University, Wakayama, Japan.
Neurosci Lett. 2020 Nov 1;738:135355. doi: 10.1016/j.neulet.2020.135355. Epub 2020 Sep 6.
Loss of the sense of touch in fingertips and toes is one of the earliest sensory dysfunctions in patients receiving chemotherapy with anti-cancer drugs such as vincristine. However, mechanisms underlying this chemotherapy-induced sensory dysfunction is incompletely understood. Whisker hair follicles are tactile organs in non-primate mammals which are functionally equivalent to human fingertips. Here we used mouse whisker hair follicles as a model system and applied the pressure-clamped single-fiber recording technique to explore how vincristine treatment affect mechanoreceptors in whisker hair follicles. We showed that in vivo treatment of mice with vincristine impaired whisker tactile behavioral responses. The pressure-clamped single-fiber recordings made from whisker hair follicle afferent nerves showed that mechanical stimulations evoked three types of mechanical responses, rapidly adapting response (RA), slowly adapting type 1 response (SA1) and slowly adapting type 2 response (SA2). Vincristine treatment significantly reduced SA1 responses but did not significantly affect RA and SA2 responses. Our findings suggest that SA1 mechanoreceptors were selectively impaired by vincristine leading to the impairment of in vivo whisker tactile behavioral responses.
指尖和脚趾失去触觉是接受长春新碱等抗癌药物化疗的患者最早出现的感觉功能障碍之一。然而，这种化疗引起的感觉功能障碍的机制尚不完全清楚。触须毛囊是无灵长类哺乳动物的触觉器官，其功能相当于人类的指尖。在这里，我们使用小鼠触须毛囊作为模型系统，并应用压力钳制单纤维记录技术来探索长春新碱治疗如何影响触须毛囊中的机械感受器。我们发现，体内给予长春新碱处理会损害小鼠的触须触觉行为反应。从触须毛囊传入神经进行的压力钳制单纤维记录显示，机械刺激引发了三种机械反应，即快速适应反应（RA）、缓慢适应型 1 反应（SA1）和缓慢适应型 2 反应（SA2）。长春新碱处理显著降低了 SA1 反应，但对 RA 和 SA2 反应没有显著影响。我们的研究结果表明，SA1 机械感受器被长春新碱选择性地损害，导致体内触须触觉行为反应受损。
