Brainstem Modulation of Caudal Trigeminal Nucleus: A Model for Understanding Migraine Biology and Future Drug Targets

There is now considerable clinical and experimental evidence implicating a role for the brainstem in migraine pathophysiology. Studies point toward a possible dysfunction in sites such as the periaqueductal gray, nucleus raphe magnus, nucleus tractus solitarius, and locus coeruleus, since these structures affect the control of anti- and pronociception as well as cerebral blood flow. Numerous neurotransmitters in these structures provide potential pharmacological targets, notably adenosine (A1), opiates, GABA, cannabinoids, cholecystokinin and compounds targeting voltage-sensitive calcium channels. The possible mechanisms by which brainstem structures could drive a dysfunction in trigeminal nociception homeostasis are reviewed.