Nitric Oxide, Perivascular Neural Transmission, and Migraine

Abstract

Migraine attacks are known to involve alterations or even dysfunction in the regulation of tone in intra-and/or extra-cranial blood vessels (Iversen et al., 1990; Friberg et al., 1991; Olesen 1991; Thomsen et al., 1995). The nature of these alterations is not clearly established, and a number of candidate neurotransmitters have been discussed (Edvinsson et al. 1988). Some of these candidates have their origin in sympathetic, parasympathetic, or sensory neurons; endothelial cells; mast cells; or on blood-borne cells. An increasing number of perivascular neurotransmitters have been detected, and their receptor mechanisms and effects have been elucidated during the last decades (Jansen-Olesen and Edvinsson, 1999). In addition, endothelium-derived relaxing factors (EDRFs) have been demonstrated; today these include nitric oxide (NO) prostaglandin I2 (PGI2) and endothelium-derived hyperpolarizing factor (EDHF).These agents are released following the stimulation of receptors located on endothelial cells or following shear-stress phenomena causing relaxation. Thus, a number of mechanisms exist for regulation of tone in cranial blood vessels. Neurogenic inflammation has been suggested as a mechanism of migraine (Moskowitz, 1993). It involves the liberation of several neuropeptides, primarily substance P (SP) and calcitonin-gene-related peptide (CGRP) (Buzzi and Moskowitz 1990). Unfortunately, neurogenic inflammation has never been shown to occur around cranial blood vessels during migraine attacks and the concentration of SP in external and internal jugular venous blood remains normal during migraine attacks (Goadsby et al., 1990; Friberg et al., 1994).