Vagus nerve stimulation inhibits trigeminal nociception in a rodent model of episodic migraine

Abstract

Noninvasive vagus nerve stimulation inhibited mechanical nociception and repressed the expression of proteins associated with sensitization of trigeminal neurons in a rodent model of episodic migraine.

Inhibition of Trigeminal Nociception by Non-invasive Vagus Nerve Stimulation: Investigating the Role of GABAergic and Serotonergic Pathways in a Model of Episodic Migraine

“…The experimental design for the first episodic migraine model was based on a prior study and involves activation of sensitized trigeminal neurons in response to exposure to a pungent odor (23). Animals were placed under 3% isoflurane and received 10 injections of 10 µl of complete Freund's adjuvant (CFA, Sigma-Aldrich, St. Louis, MO; 1:1 in 0.9% sterile saline) into the upper trapezius.…”

“…Animals were monitored for normal behaviors for a total of 8 days. To cause activation of trigeminal nociceptors, animals were exposed for 10 min to the volatile compounds from an oil extract obtained from California bay laurel tree leaves (CBL, World Spice, Seattle, WA) that was prepared as described previously (23).…”

“…The convergence in the upper spinal cord of nerves providing sensory innervation of neck/shoulder muscles and those emanating from the trigeminal ganglion may explain why neck/shoulder pathology is often cited as a risk factor for orofacial pain conditions including migraine (21,22). In support of this notion, neck muscle inflammation has been reported to promote sensitization of primary trigeminal neurons so that exposure to a known migraine trigger, the pungent odor from a CBL leaf extract, was sufficient to cause an increase in trigeminal nociception in response to mechanical stimulation (23). One of the main active molecules in CBL trees leaves is umbellulone, which has been shown to cause activation of TRPA1, the subsequent release of CGRP, and to increase trigeminal nociception (17).…”

A Review of Spinal and Peripheral Neuromodulation and Neuroinflammation: Lessons Learned Thus Far and Future Prospects of Biotype Development

“…The effects of VNS have also been studied in the treatment of other pain‐inducing conditions such as migraines, osteoarthritis, and Crohn's disease. In animal studies, VNS decreased pain‐induced activation of neurons in the trigeminal nucleus caudalis in addition to reducing pain behavior and trigeminal allodynia . Case report data from patients with invasive VNS, uncontrolled small‐scale clinical studies and larger RCT's (EVENT, PRESTO) investigating nVNS have shown a reduced number of headaches per day and decreased pain intensity scores (preventive use).…”

Saliva molecular inflammatory profiling in female migraine patients responsive to adjunctive cervical non-invasive vagus nerve stimulation: the MOXY Study

“…Of note, t-VNS duration lasted for 4 h per day during the 3 months study period [19]. In order to parallel acute and chronic head pain and to investigate possible VNS-induced changes in the trigemino-nociceptive system, several preclinical studies confirmed the clinical observed VNS responsiveness, although the precise pathways are not fully understood [20][21][22][23][24][25][26][27][28].…”