Neurogenic nitric oxide facilitates the central nociceptive transmission of migraine attacks

摘要

Recent studies have shown that nitric oxide(NO) can induce migraine attacks at three possible sites of action:nitroxidergic nerves,the vascular endothelium,and the central nervous system.Most previous studies have focused on the former two sites of action.Several experiments using exogenic NO donors have suggested that nitroglycerin may induce migraine via central mechanisms.However,few studies have investigated the source of the NO involved in the central mechanisms of migraine.The present study used a cat model of migraine to represent migraine attacks in humans.We performed immunochemical staining of successive frozen sections of the brainstem and upper cervical spinal cord,and then used c-Fos protein expression to label nerve cell activation.We observed the effects of Nω-nitro-L-arginine methyl ester(L-NAME),a non-selective nitric oxide synthase(NOS) inhibitor,and 7-nitroindozole(7-NI),a selective neuronal NOS inhibitor,on c-Fos and nNOS expression,which were induced by electrical stimulation to the dura mater near the superior sagittal sinus.The results demonstrated that c-Fos or nNOS immunoreactive cells was concentrated in the superficial layers(laminae I and II) of the spinal nucleus of trigeminal nerve.L-NAME and 7-NI pre-treatment significantly decreased c-Fos and neurogenic NOS expression;and there was a significant linear correlation between c-Fos and NOS expression(r = 0.858 2,P < 0.01).These findings suggest that neurogenic NO could facilitate migraine nociceptive transmission to second-order neurons of the trigeminal nerve.However,L-NAME and 7-NI may block the activation of neurons in the spinal nucleus of the trigeminal nerve by inhibiting NO synthesis,and thereby attenuate acute migraine attacks.