Akerman Simon, Simon Bruce, Romero-Reyes Marcela
Department of Oral and Maxillofacial Pathology, Radiology and Medicine, New York University College of Dentistry, NY 10010, USA.
electroCore LLC, Basking Ridge, NJ 07920, USA.
Neurobiol Dis. 2017 Jun;102:96-104. doi: 10.1016/j.nbd.2017.03.004. Epub 2017 Mar 9.
Vagus nerve stimulation (VNS) has been reported to be effective in the abortive treatment of both migraine and cluster headache. Using validated animal models of acute dural-intracranial (migraine-like) and trigeminal-autonomic (cluster-like) head pain we tested whether VNS suppresses ongoing and nociceptive-evoked firing of trigeminocervical neurons to explain its abortive effects in migraine and cluster headache. Unilateral VNS was applied invasively via hook electrodes placed on the vagus nerve. A single dose of ipsilateral or contralateral VNS, to trigeminal recording and dural-stimulating side, suppressed ongoing spontaneous and noxious dural-evoked trigeminocervical neuronal firing. This effect was dose-dependent, with two doses of ipsilateral VNS prolonging suppression of ongoing spontaneous firing (maximally by ~60%) for up to three hours, and dural-evoked (Aδ-fiber; by ~22%, C-fiber: by ~55%) responses for at least two hours. Statistically, there was no difference between ipsilateral and contralateral groups. Two doses of VNS also suppressed superior salivatory nucleus-evoked trigeminocervical neuronal responses (maximally by ~22%) for 2.5h, to model nociceptive activation of the trigeminal-autonomic pathway. VNS had no effect on normal somatosensory cutaneous facial responses throughout. These studies provide a mechanistic rationale for the observed benefits of VNS in the abortive treatment of migraine and cluster headache. In addition, they further validate these preclinical models as suitable approaches to optimize therapeutic efficacy, and provide an opportunity to hypothesize and dissect the neurobiological mechanisms of VNS in the treatment of primary headaches.
据报道，迷走神经刺激（VNS）在偏头痛和丛集性头痛的预防性治疗中均有效。我们使用经过验证的急性硬脑膜-颅内（偏头痛样）和三叉神经-自主神经（丛集样）头痛的动物模型，测试VNS是否能抑制三叉神经颈神经元的持续放电和伤害性诱发的放电，以解释其在偏头痛和丛集性头痛预防性治疗中的作用。通过置于迷走神经上的钩状电极进行侵入性单侧VNS。对三叉神经记录侧和硬脑膜刺激侧给予单剂量的同侧或对侧VNS，可抑制持续的自发性和伤害性硬脑膜诱发的三叉神经颈神经元放电。这种效应具有剂量依赖性，两剂同侧VNS可将持续自发性放电的抑制时间延长至3小时（最大约60%），并将硬脑膜诱发的反应（Aδ纤维：约22%，C纤维：约55%）抑制至少2小时。在统计学上，同侧组和对侧组之间没有差异。两剂VNS还可抑制上涎核诱发的三叉神经颈神经元反应（最大约22%）达2.5小时，以模拟三叉神经-自主神经通路的伤害性激活。VNS对正常的面部躯体感觉皮肤反应始终没有影响。这些研究为VNS在偏头痛和丛集性头痛预防性治疗中观察到的益处提供了机制依据。此外，它们进一步验证了这些临床前模型是优化治疗效果的合适方法，并为推测和剖析VNS治疗原发性头痛的神经生物学机制提供了机会。
