title: Vagus nerve stimulation suppresses acute noxious activation of trigeminocervical neurons in animal models of primary headache.
abstract: 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.
authors.affiliation: Department of Oral and Maxillofacial Pathology, Radiology and Medicine, New York University College of Dentistry, NY 10010, USA. Electronic address: simon.akerman@nyu.edu.
authors.forename: Simon
authors.initials: S
authors.lastname: Akerman
authors.affiliation: electroCore LLC, Basking Ridge, NJ 07920, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Simon
authors.affiliation: Department of Oral and Maxillofacial Pathology, Radiology and Medicine, New York University College of Dentistry, NY 10010, USA.
authors.forename: Marcela
authors.initials: M
authors.lastname: Romero-Reyes
mesh_terms: D000200:Action Potentials; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D004388:Dura Mater / Q000503:physiopathology; D004567:Electrodes, Implanted; D007839:Functional Laterality / Q000502:physiology; D006261:Headache / Q000503:physiopathology* / Q000628:therapy*; D008297:Male; D009474:Neurons / Q000502:physiology*; D059226:Nociceptive Pain / Q000503:physiopathology / Q000628:therapy; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D014278:Trigeminal Nuclei / Q000503:physiopathology*; D055536:Vagus Nerve Stimulation / Q000379:methods
keywords: Cluster headache; Migraine; Trigeminal autonomic; Trigeminovascular; Vagus nerve stimulation