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.