Headache mechanisms

Abstract

Headache disorders involve widespread disturbances in nervous system function, resulting in a broad array of symptoms in addition to head pain. A general understanding of these disorders requires not only an understanding of the mechanisms underlying the pain, but also of those causing symptoms that may precede, accompany, or follow the pain. Imaging and clinical electrophysiological studies provide strong evidence that rather than being primarily vascular disorders, the major primary headaches disorders are fundamentally disorders of brain excitability. Changes in the activity of the thalamus and cortex appear to be particularly important in migraine, and alterations in hypothalamic function likely play a critical role in both migraine and cluster headache. Migraine aura involves propagated waves of activity in the cortex; cortical spreading depression (CSD) in animal models provides insight in the mechanisms of these waves. Elevations of extracellular potassium and release of the excitatory transmitter glutamate appear to be critical in the initiation of CSD, whereas sustained uncoupling of the normal relationship between neural and vascular activity occurs in the wake of CSD. Headache pain may be transmitted not only by trigeminal nerves, but also by the upper cervical nerves. The trigeminal nucleus caudalis, dorsolateral pons and midbrain, periaqueductal gray, thalamus, and sensory cortex may all play important roles in headache. Increasing evidence implicates the release of neuropeptides, particularly calcitonin gene-related peptide as a primary mediator of headache. Each of these and other basic mechanisms of headache may represent distinct therapeutic targets