Bartsch T, Levy M J, Knight Y E, Goadsby P J
Headache Group, Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.
Pain. 2004 Jun;109(3):367-378. doi: 10.1016/j.pain.2004.02.005.
The novel neuropeptides orexin A and B are selectively synthesised in the lateral and posterior hypothalamus and are involved in hypothalamic regulation of autonomic and neuroendocrine functions. Recent findings point also to a role in nociception. As the posterior hypothalamus is involved in the central modulation of nociception we studied the effects of hypocretin/orexin receptor activation in the posterior hypothalamic area (PH) of the rat on dural nociceptive input. Orexins were microinjected into the PH and the effects on responses of neurones in the caudal trigeminal nucleus studied. Injection of orexin A decreased the A- and C-fibre responses to dural electrical stimulation as well as spontaneous activity. Responses to noxious thermal stimulation of the facial skin were also decreased by orexin A. Injection of orexin B into the PH, however, elicited increased responses to dural stimulation in A- and C-fibre responses and resulted in increased spontaneous activity. Responses to facial thermal stimulation were also increased by orexin B. Control injection of saline into the PH had no significant effect. The results show a differential modulation of dural nociceptive input by orexin A and B receptor activation in the PH. The results support the role of the PH in the nociceptive processing of meningeal input. As both peptides are also involved in hypothalamic regulation of neuroendocrine and autonomic functions, orexinergic mechanisms in the PH may provide a link for endocrine and autonomic changes as well as nociceptive phenomena seen in primary headache disorders.
新型神经肽食欲素A和B在下丘脑外侧和后部选择性合成，并参与下丘脑对自主神经和神经内分泌功能的调节。最近的研究结果还表明其在伤害感受中发挥作用。由于下丘脑后部参与伤害感受的中枢调节，我们研究了在大鼠下丘脑后部区域（PH）激活下丘脑泌素/食欲素受体对硬脑膜伤害性传入的影响。将食欲素微量注射到PH中，并研究其对尾侧三叉神经核中神经元反应的影响。注射食欲素A可降低A纤维和C纤维对硬脑膜电刺激的反应以及自发活动。食欲素A还可降低对面部皮肤有害热刺激的反应。然而，将食欲素B注射到PH中，可引起A纤维和C纤维对硬脑膜刺激的反应增加，并导致自发活动增加。食欲素B也可增加对面部热刺激的反应。向PH中注射生理盐水作为对照，没有显著影响。结果表明，PH中食欲素A和B受体激活对硬脑膜伤害性传入具有不同的调节作用。这些结果支持了PH在脑膜传入伤害感受处理中的作用。由于这两种肽也参与下丘脑对神经内分泌和自主神经功能的调节，PH中的食欲素能机制可能为原发性头痛疾病中出现的内分泌和自主神经变化以及伤害感受现象提供一个联系。
