Basic Science: Mechanisms of Medication Overuse Headache

Headache caused by overuse of symptomatic medications to treat headache represents a challenging clinical problem. Recent studies exploring both the mechanisms of migraine headache and neuroplastic changes following sustained exposure to analgesic drugs suggest insights regarding the pathophysiology of medication overuse headache. In this review, changes that occur following chronic morphine that may be particularly relevant to the induction of medication overuse headache will be discussed. Peripherally, these changes include increased expression of calcitonin gene-related peptide (CGRP) in primary afferent neurons. Centrally, they include increased descending facilitation from the rostral ventromedial medulla and increased excitatory neurotransmission at the level of the dorsal horn. Interestingly, many of these same changes, including increased CGRP levels and peripheral and central sensitization, are apparent in inflammatory pain states. Recent revelations into the mechanisms of migraine headache suggest that neurogenic inflammation leads to both peripheral and central sensitization in the migraine sufferer. Furthermore, CGRP plays a prominent role in initiating vasodilation of the intracranial blood vessels and subsequent headache. Given the many parallels between the effects of chronic morphine exposure and processes that occur during migraine, it is evident that overuse of symptomatic medications to treat headache could lead to worsening of symptoms. In animals, the neural adaptations that occur after sustained morphine exposure are manifested behaviorally as an increased sensitivity to both tactile and thermal stimulation. In the headache sufferer, these adaptations could lead to medication overuse headache.