Wolfson Centre for Age Related Diseases, King's College London, UK Department of Neurology, Royal Free Hospital, London, UK Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK.
Pain. 2013 Sep;154(9):1569-1577. doi: 10.1016/j.pain.2013.04.030. Epub 2013 Apr 18.
TRPA1 is an ion channel of the TRP family that is expressed in some sensory neurons. TRPA1 activity provokes sensory symptoms of peripheral neuropathy, such as pain and paraesthesia. We have used a grease gap method to record axonal membrane potential and evoked compound action potentials (ECAPs) in vitro from human sural nerves and studied the effects of mustard oil (MO), a selective activator of TRPA1. Surprisingly, we failed to demonstrate any depolarizing response to MO (50, 250 μM) in any human sural nerves. There was no effect of MO on the A wave of the ECAP, but the C wave was reduced at 250 μM. In rat saphenous nerve fibres MO (50, 250 μM) depolarized axons and reduced the C wave of the ECAP but had no effect on the A wave. By contrast, both human and rat nerves were depolarized by capsaicin (0.5 to 5 μM) or nicotine (50 to 200 μM). Capsaicin caused a profound reduction in C fibre conduction in both species but had no effect on the amplitude of the A component. Lidocaine (30 mM) depolarized rat saphenous nerves acutely, and when rat nerves were pretreated with 30 mM lidocaine to mimic the exposure of human nerves to local anaesthetic during surgery, the effects of MO were abolished whilst the effects of capsaicin were unchanged. This study demonstrates that the local anaesthetic lidocaine desensitizes TRPA1 ion channels and indicates that it may have additional mechanisms for treating neuropathic pain that endure beyond simple sodium channel blockade.
TRPA1 是一种 TRP 家族的离子通道，在一些感觉神经元中表达。TRPA1 活性引发周围神经病变的感觉症状，如疼痛和感觉异常。我们使用油脂间隙法记录体外人腓肠神经的轴突膜电位和诱发复合动作电位 (ECAP)，并研究了芥末油 (MO) 的作用，MO 是 TRPA1 的选择性激活剂。令人惊讶的是，我们未能在任何人类腓肠神经中证明 MO（50、250 μM）有任何去极化反应。MO 对 ECAP 的 A 波没有影响，但在 250 μM 时 C 波减少。在大鼠隐神经纤维中，MO（50、250 μM）使轴突去极化并减少 ECAP 的 C 波，但对 A 波没有影响。相比之下，MO（0.5 至 5 μM）或尼古丁（50 至 200 μM）均可使人和大鼠神经去极化。辣椒素在两种物种中均导致 C 纤维传导的显著减少，但对 A 成分的幅度没有影响。利多卡因（30 mM）使大鼠隐神经急性去极化，当用 30 mM 利多卡因预处理大鼠神经以模拟手术中局部麻醉剂暴露于人神经时，MO 的作用被消除，而辣椒素的作用保持不变。本研究表明，局部麻醉剂利多卡因使 TRPA1 离子通道脱敏，并表明它可能具有治疗神经病理性疼痛的额外机制，这种机制超越了单纯的钠通道阻断。
