Differential medication overuse risk of novel anti-migraine therapeutics.

Medication overuse headache is estimated to affect 2% of the population, and is ranked in the top 20 most disabling disorders due to its high level of disability. Several therapies used in the treatment of acute migraine are thought to be associated with medication overuse headache, including opioids and triptans. With limited treatment options, it is critical to determine the risk profile of novel therapies prior to their widespread use.

The role of the brainstem in migraine: Potential brainstem effects of CGRP and CGRP receptor activation in animal models.

Background: Migraine is a severe debilitating disorder of the brain that is ranked as the sixth most disabling disorder globally, with respect to disability adjusted life years, and there remains a significant unmet demand for an improved understanding of its underlying mechanisms. In conjunction with perturbed sensory processing, migraine sufferers often present with diverse neurological manifestations (premonitory symptoms) that highlight potential brainstem involvement. Thus, as the field moves away from the view of migraine as a consequence of purely vasodilation to a greater understanding of migraine as a complex brain disorder, it is critical to consider the underlying physiology and pharmacology of key neural networks likely involved.

Serotonin depletion can enhance the cerebrovascular responses induced by cortical spreading depression via the nitric oxide pathway.

Serotonin (5-HT) is an important neurotransmitter involved in the control of neural and vascular responses. 5-HT depletion can induce several neurological disorders, including migraines. Studies on a cortical spreading depression (CSD) migraine animal model showed that the cortical neurons sensitivity, vascular responses, and nitric oxide (NO) production were significantly increased in 5-HT depletion.

Serotonin depletion leads to cortical hyperexcitability and trigeminal nociceptive facilitation via the nitric oxide pathway.

Objective: To investigate the role of nitric oxide (NO) in the development of cortical hyperexcitability and trigeminal nociceptive facilitation induced by serotonin (5-HT) depletion.

Background: Nitric oxide and 5-HT are important in the pathogenesis of primary headaches. An increase in cortical excitability and trigeminal nociception has been demonstrated in animals with low 5-HT levels.