Activation of 5-HT1B/1D receptor in the periaqueductal gray inhibits nociception
Activation of 5-HT1B/1D receptor in the periaqueductal gray inhibits nociception
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DOI：
10.1002/ana.20193
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发表时间：
2004-09-01
影响因子：
11.2
通讯作者：
Goadsby, PJ
中科院分区：
文献类型：
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作者：
Bartsch, T;Knight, YE;Goadsby, PJ
据认为，作用于5-羟色胺5-HT 1B/1D受体（曲坦类）的无效抗偏头痛化合物的作用部位是三叉神经血管系统。我们测试了是否存在非三叉神经的作用部位。将5-HT 1B/1D激动剂那拉曲普坦微量注射到腹外侧导水管周围灰质（vlPAG）中，并监测三叉神经尾侧核（TNC）中的活性。记录了20个TNC背角的伤害性神经元，接受来自硬脑膜和面部的会聚输入。观察了注射那拉曲普坦前后神经元对硬脑膜、面部皮肤和角膜刺激的反应。那拉曲普坦降低硬膜对电刺激的兴奋性。A纤维反应降低24 +/- 4.1%（p < 0.001），C纤维反应降低42 +/- 8.2%（p < 0.001）。自发活动减少38 +/- 7.5%（p < 0.001）。注药后硬脑膜的机械阈值从（n = 14，p < 0.01）增加到（n = 14，p < 0.01）。注射那拉曲普坦不会改变对面部和角膜刺激的反应。这些结果表明，vlPAG中的5-HT 1B/1D受体活化激活抑制硬脑膜但不抑制面部和角膜伤害性输入的下行疼痛调节通路。这些研究结果的理解曲坦类药物在偏头痛和丛集性头痛的作用的影响，表明大脑位点以外的三叉神经核可能发挥作用的曲坦类药物的临床作用。
It is considered that the site of action of the abortive antimigraine compounds acting at serotonin, 5-HT1B/1D, receptors (triptans) is the trigeminovascular system. We tested whether there is a non-trigeminal site of action. The 5-HT1B/1D agonist, naratriptan, was microinjected into the ventrolateral periaqueductal gray (vlPAG), and activity in the trigeminal nucleus caudalis (TNC) was monitored. Recordings were made from 20 nociceptive neurons in the dorsal horn of the TNC that received convergent input from the dura mater and face. Responses of neurons to dural, facial cutaneous and corneal stimulation were studied before and after injection of naratriptan. Naratriptan decreased the excitability to electrical stimulation of the dura. mater as the A-fiber response decreased by 24 +/- 4.1% (p < 0.001) and the C-fiber response decreased by 42 +/- 8.2% (p < 0.001). Spontaneous activity was decreased by 38 +/- 7.5% (p < 0.001). After injection, the mechanical thresholds of the dura mater increased from (n = 14, p < 0.01). Responses to stimulation of the face and cornea were not altered by injection of naratriptan. These results suggest that 5-HT1B/1D receptor activation in the vlPAG activates descending pain-modulating pathways that inhibit dural, but not facial and corneal nociceptive input. These findings have implications for the understanding of the action of triptans in migraine and cluster headache, suggesting that brain loci other than the trigeminal nucleus may play a role in the clinical action of triptans.