Migraine is a prevalent neurological disorder. The anatomical structure responsible for the pain caused by migraine is the trigeminovascular system. Carbon monoxide (CO) is a gas that can induce headache due to its toxicity, but when produced endogenously can regulate cerebral blood flow, nociception and neurotransmission; however, its role in the trigeminovascular system has not been investigated. The aim of our study was to analyze the effects of exogenous CO on the TRPV1 receptor-mediated activity of the rat TG nerve.

Action potentials (APs) of the trigeminal nerve were recorded using na extracellular electrode in a rat hemi-skull preparation. Capsaicin (1 µM) was used as an agonist of TRPV1 receptors; CORM-II (60 µM) was used as a CO donor, and MDL 12,330A (10 µM) was used as an inhibitor of adenylyl cyclase.

In control conditions, trigeminal nerve afferents demonstrated spontaneous regular activity. The application of the CO donor CORM-II resulted in a significant increase in the frequency of APs. The application of capsaicin induced a significant increase in the frequency of APs, which persisted for approximately one to two minutes until the TRPV1 receptors became desensitized. Application of capsaicin after incubation in CORM-II increased the duration of the capsaicine effect to 4-6 minutes. Preliminary inhibition of adenylyl cyclase by MDL prevented this effect.

In conclusion, the CO donor has pro-nociceptive effects on the afferents of the trigeminal nerve, and promotes TRPV1 receptor-mediated activity through adenylate cyclase. Further investigation is necessary to reveal the mechanisms of CO action in the trigemino-vascular system and its impact in nociception.

This work was supported by the Russian Science Foundation (№ 20-15-00100)