Akerman S, Kaube H, Goadsby P J
Headache Group, Institute of Neurology, Queen Square, London WCIN 3BG.
Br J Pharmacol. 2003 Oct;140(4):718-24. doi: 10.1038/sj.bjp.0705486.
Capsaicin, the active substance in chilli peppers, activates the vanilloid type 1 receptor (VR1) rather than the vanilloid-like receptor (VRL1) in the trigeminal ganglion and nucleus of small and medium C- and Adelta-fibres. Capsaicin induces calcitonin gene-related peptide (CGRP) release when VR1 receptors are activated, and this can be reversed by both the VR1 receptor antagonist capsazepine and the CGRP blocker alphaCGRP8-37 in vitro. In this study we used intravital microscopy to look at the possible role of the VR1 receptor in the trigeminovascular system in producing dilation of dural blood vessels. Capsazepine (3 mg kg-1) was given to study the effect of the VR1 receptor in dural vessel dilation produced by either electrical stimulation, CGRP (1 microg x kg-1) or capsaicin (7 microg x kg-1) bolus injection. We also looked at the effect of the CGRP blocker alphaCGRP8-37 (300 microg x kg-1) on capsaicin-induced dilation so that we could see if the results found in vitro could also be found in vivo. Electrical stimulation of the dura mater produced a robust vasodilator response between 130 and 137% of baseline diameter that was no different across four repeat stimuli (F3,18=0.6, P=0.61). CGRP similarly produced a dilatation of 99-111% that was no different across four baseline infusions (F3,15=2.4, P=0.113). Capsaicin also produced a consistent dilation of between 112 and 120% of baseline across three injections (F2,10=0.6, P=0.567). Capsazepine did not inhibit the dilation brought about by either electrical stimulation or CGRP injection, while it was able to inhibit the dilation brought about by capsaicin (t5=3.4, P<0.05). AlphaCGRP8-37 also inhibited the capsaicin-induced dilation (t5=7.4, P<0.05) probably inhibiting the action of released CGRP at the CGRP receptor. The study demonstrates that capsaicin can repeatedly induce dural vessel dilation in vivo, presumably through inducing CGRP release from trigeminal sensory nerve fibres, while C-fibres may have been desensitised. The data imply that the VR1 receptor plays only a minor role in trigeminovascular-induced dural vessel dilation.
辣椒素是辣椒中的活性物质，它激活三叉神经节以及中小C纤维和Aδ纤维的细胞核中的1型香草酸受体（VR1），而非类香草酸受体（VRL1）。当VR1受体被激活时，辣椒素会诱导降钙素基因相关肽（CGRP）释放，在体外，VR1受体拮抗剂辣椒平以及CGRP阻滞剂αCGRP8 - 37均可逆转这种释放。在本研究中，我们使用活体显微镜观察VR1受体在三叉神经血管系统中引起硬脑膜血管扩张可能发挥的作用。给予辣椒平（3毫克/千克），以研究VR1受体对电刺激、CGRP（1微克/千克）或辣椒素（7微克/千克）推注所产生的硬脑膜血管扩张的影响。我们还观察了CGRP阻滞剂αCGRP8 - 37（300微克/千克）对辣椒素诱导的血管扩张的影响，以便了解体外研究结果是否也适用于体内。对硬脑膜进行电刺激可产生强烈的血管舒张反应，血管直径达到基线直径的130%至137%，在四次重复刺激中无差异（F3,18 = 0.6，P = 0.61）。CGRP同样可产生99%至111%的扩张，在四次基线输注中无差异（F3,15 = 2.4，P = 0.113）。辣椒素在三次注射中也可使血管持续扩张至基线的112%至120%（F2,10 = 0.6，P = 0.567）。辣椒平并未抑制电刺激或CGRP注射所引起的血管扩张，但能够抑制辣椒素引起的血管扩张（t5 = 3.4，P < 0.05）。αCGRP8 - 37也抑制了辣椒素诱导的血管扩张（t5 = 7.4，P < 0.05），可能是通过抑制释放的CGRP在CGRP受体上的作用。该研究表明，辣椒素在体内可反复诱导硬脑膜血管扩张，推测是通过诱导三叉神经感觉神经纤维释放CGRP实现的，而C纤维可能已发生脱敏。数据表明，VR1受体在三叉神经血管诱导的硬脑膜血管扩张中仅起次要作用。
