UCSF Headache Program, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
Pain. 2012 Nov;153(11):2226-2232. doi: 10.1016/j.pain.2012.07.006. Epub 2012 Aug 14.
The transient receptor potential vanilloid channel 1 (TRPV1) is a nociceptive transducer located on nociceptive neurons. TRPV1 channels located on peripheral neurons mainly transduce the sense of heat and are also activated by low pH or capsaicin. The role of centrally located TRPV1 channels is not fully understood. Likewise their importance in pain syndromes of central origin, such as migraine, is not known. Experimental data suggest a relationship to migraine. However, experimental studies with TRPV1 receptor antagonists indicate that the receptor may not be a useful target for new acute migraine treatments. Any potential role for the receptor in the chronification of migraine has not been investigated. The present study aimed at analyzing the use of the TRPV1 channel as a target to desensitize trigeminal neurons and thereby inhibit neuronal activity in the trigeminocervical complex. The TRPV1 receptor agonist olvanil was used for desensitization because, as compared with capsaicin, it is non-noxious and lacks capsaicin's pungency and CGRP release potential. We further investigated a possible effect of olvanil on cannabinoid (CB(1)) receptors, as an interaction between both receptor systems has been described previously. The results show that olvanil dose-dependently inhibited spontaneous and stimulus-induced activity within the trigeminocervical complex, whereas it had no effect on CSD susceptibility. We further demonstrated that the inhibiting effect of olvanil is mediated by vanilloid and cannabinoid receptor systems, thereby using the synergistic effects this dual mechanism offers. Curiously, TRPV1 receptor agonism may have anti-nociceptive properties through central mechanisms that would be of considerable interest to elucidate.
瞬时受体电位香草酸通道 1（TRPV1）是一种位于伤害性神经元上的伤害性感受器转导蛋白。位于周围神经元上的 TRPV1 通道主要转导热感觉，也可被低 pH 值或辣椒素激活。中枢定位的 TRPV1 通道的作用尚未完全阐明。同样，它们在偏头痛等中枢起源的疼痛综合征中的作用也不清楚。实验数据表明其与偏头痛有关。然而，TRPV1 受体拮抗剂的实验研究表明，该受体可能不是新的急性偏头痛治疗的有用靶点。该受体在偏头痛慢性化中的潜在作用尚未得到研究。本研究旨在分析将 TRPV1 通道作为脱敏三叉神经神经元的靶点，从而抑制三叉神经颈复合体中的神经元活动。TRPV1 受体激动剂 olvanil 用于脱敏，因为与辣椒素相比，它无刺激性且缺乏辣椒素的刺激性和 CGRP 释放潜力。我们进一步研究了 olvanil 对大麻素（CB(1)）受体的可能影响，因为先前已经描述了这两个受体系统之间的相互作用。结果表明，olvanil 剂量依赖性地抑制三叉神经颈复合体中的自发性和刺激诱导性活动，而对 CSD 易感性没有影响。我们进一步证明，olvanil 的抑制作用是通过香草素和大麻素受体系统介导的，从而利用了这种双重机制的协同作用。奇怪的是，TRPV1 受体激动剂可能通过中枢机制产生抗伤害感受特性，这将是阐明偏头痛的重要研究方向。
