Anandamide is able to inhibit trigeminal neurons using an in vivo model of trigeminovascular-mediated nociception
Anandamide is able to inhibit trigeminal neurons using an in vivo model of trigeminovascular-mediated nociception
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DOI：
10.1124/jpet.103.059808
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发表时间：
2004-04-01
影响因子：
3.5
通讯作者：
Goadsby, PJ
中科院分区：
文献类型：
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作者：
Akerman, S;Kaube, H;Goadsby, PJ
花生四烯乙醇酰胺（anandamide，AEA）被认为是大麻素CB 1和CB 2受体的内源性配体。CB 1受体已被发现定位于三叉神经脊束和三叉神经脊束核尾侧的纤维上。大麻素的已知行为效应是抗伤害感受、僵硬、体温过低和运动活动抑制，类似于大麻的精神活性成分δ（9）-四氢坎南醇。它可能是治疗偏头痛的一个可能的靶点。在这项研究中，我们研究了CB 1受体在三叉神经血管系统中的可能作用，使用活体显微镜研究了anandamide对各种血管扩张剂的影响。Anandamide能够抑制由电刺激引起的硬脑膜血管扩张50%，降钙素基因相关肽（CGRP）30%，辣椒素45%，一氧化氮40%。CGRP（8-37）也能够使一氧化氮（NO）诱导的扩张减弱50%。CB 1受体拮抗剂AM 251可逆转大麻素的抑制作用。Anandamide还能降低CGRP引起的血压变化，这种作用不能被AM 251逆转。看来大麻素既在突触前起作用，防止三叉神经感觉纤维释放CGRP，又在突触后抑制CGRP诱导的硬脑膜动脉平滑肌NO释放。CB 1受体似乎参与了NO/CGRP关系，该关系存在于引起头痛和硬脑膜血管扩张中。另外，anandamide引起的一些血压变化似乎是由非大麻素受体介导的，因为AM 251无法逆转这些作用。可以认为，大麻素是紧张性释放的，在三叉神经血管系统中发挥某种形式的调节作用。
Arachidonylethanolamide (anandamide, AEA) is believed to be the endogenous ligand of the cannabinoid CB1 and CB2 receptors. CB1 receptors have been found localized on fibers in the spinal trigeminal tract and spinal trigeminal nucleus caudalis. Known behavioral effects of anandamide are antinociception, catalepsy, hypothermia, and depression of motor activity, similar to Delta(9)-tetrahydocannanbinol, the psychoactive constituent of cannabis. It may be a possible therapeutic target for migraine. In this study, we looked at the possible role of the CB1 receptor in the trigeminovascular system, using intravital microscopy to study the effects of anandamide against various vasodilator agents. Anandamide was able to inhibit dural blood vessel dilation brought about by electrical stimulation by 50%, calcitonin gene-related peptide (CGRP) by 30%, capsaicin by 45%, and nitric oxide by 40%. CGRP(8-37) was also able to attenuate nitric oxide (NO)-induced dilation by 50%. The anandamide inhibition was reversed by the CB1 receptor antagonist AM251. Anandamide also reduced the blood pressure changes caused by CGRP injection, this effect was not reversed by AM251. It would seem that anandamide acts both presynaptically, to prevent CGRP release from trigeminal sensory fibers, and postsynaptically to inhibit the CGRP-induced NO release in the smooth muscle of dural arteries. CB1 receptors seem to be involved in the NO/CGRP relationship that exists in causing headache and dural blood vessel dilation. It also seems that some of the blood pressure changes caused by anandamide are mediated by a noncannabinoid receptor, as AM251 was unable to reverse these effects. It can be suggested that anandamide is tonically released to play some form of modulatory role in the trigeminovascular system.