Endocannabinoids in the Brainstem Modulate Dural Trigeminovascular Nociceptive Traffic via CB1 and "Triptan" Receptors: Implications in Migraine
Endocannabinoids in the Brainstem Modulate Dural Trigeminovascular Nociceptive Traffic via CB1 and "Triptan" Receptors: Implications in Migraine
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DOI：
10.1523/jneurosci.0943-13.2013
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发表时间：
2013-09-11
影响因子：
5.3
通讯作者：
Goadsby, Peter J.
中科院分区：
文献类型：
--
作者：
Akerman, Simon;Holland, Philip R.;Goadsby, Peter J.
三叉神经血管伤害性通路的激活和敏化被认为是偏头痛剧烈和搏动性疼痛的神经基础。众所周知，内源性大麻素除了具有生理止痛剂的作用外，还能抑制硬脑膜三叉神经血管的伤害性反应。它们还参与脑干对皮肤诱发的C纤维脊髓伤害性反应的下行调制。本研究的目的是确定内源性大麻素是否参与脑干腹外侧导水管周围灰质(VlPAG)对硬脑膜和/或皮肤三叉神经血管伤害性反应的下行调制。激活vlPAG的CB1受体可减弱硬脑膜诱发的A-增量纤维神经元(最大减弱19%)和大鼠三叉神经颈复合体的基础自发活动(最大减弱33%)，但对皮肤面部感受野反应无影响。通过vlPAG给予特异性CB1受体拮抗剂，或局部或全身给予5-HT1B/1D受体拮抗剂，可抑制这种抑制性vlPAG介导的调制。这些发现首次证明，脑干内源性大麻素对基础三叉神经血管神经元张力和A-增量纤维硬脑膜伤害性反应提供下行调制，这与脑干调节脊髓伤害性信息传递的方式不同。此外，我们的数据表明，在躯体感觉伤害性信息的处理过程中，5-羟色胺能系统和内源性大麻素系统之间存在着一种新的相互作用，这表明雷公藤多糖的一些治疗作用可能是通过vlPAG中含有内源性大麻素的神经元来实现的。
Activation and sensitization of trigeminovascular nociceptive pathways is believed to contribute to the neural substrate of the severe and throbbing nature of pain in migraine. Endocannabinoids, as well as being physiologically analgesic, are known to inhibit dural trigeminovascular nociceptive responses. They are also involved in the descending modulation of cutaneous-evoked C-fiber spinal nociceptive responses from the brainstem. The purpose of this study was to determine whether endocannabinoids are involved in the descending modulation of dural and/or cutaneous facial trigeminovascular nociceptive responses, from the brainstem ventrolateral periaqueductal gray (vlPAG). CB1 receptor activation in the vlPAG attenuated dural-evoked A delta-fiber neurons (maximally by 19%) and basal spontaneous activity (maximally by 33%) in the rat trigeminocervical complex, but there was no effect on cutaneous facial receptive field responses. This inhibitory vlPAG-mediated modulation was inhibited by specific CB1 receptor antagonism, given via the vlPAG, and with a 5-HT1B/1D receptor antagonist, given either locally in the vlPAG or systemically. These findings demonstrate for the first time that brainstem endocannabinoids provide descending modulation of both basal trigeminovascular neuronal tone and A delta-fiber dural-nociceptive responses, which differs from the way the brainstem modulates spinal nociceptive transmission. Furthermore, our data demonstrate a novel interaction between serotonergic and endocannabinoid systems in the processing of somatosensory nociceptive information, suggesting that some of the therapeutic action of triptans may be via endocannabinoid containing neurons in the vlPAG.