Medication overuse headache (MOH) is a challenging, debilitating disorder that develops from the frequent use of medications taken for the treatment of
migraine headache pain. MOH affects an estimated 3-5% of the general population. The mechanisms underlying the development of MOH remain unknown.
Opiates are one of the major classes of medications used for the treatment of
migraine at least in some countries, including the USA. Although the effects of repeated
opiate use for
headache are unknown, it is possible that
opiate use may contribute to increased frequency and occurrence of such
headaches. Recent preclinical studies exploring the neuroadaptive changes following sustained exposure to
morphine may give some insights into possible causes of MOH. Peripherally, these changes include increased expression of
calcitonin gene-related peptide (CGRP) in trigeminal primary afferent neurons. Centrally, they include increased excitatory neurotransmission at the level of the dorsal horn and nucleus caudalis. Critically, these neuroadaptive changes persist for long periods of time and the evoked release of CGRP is enhanced following
morphine pretreatment. Stimuli known to elicit
migraine, such as
nitric oxide donors or stress, produce
hyperalgesia in
morphine- but not in saline-pretreated rats even long after the discontinuation of the
opiate. CGRP plays a prominent role in initiating vasodilation of the intracranial blood vessels and subsequent
headache. Furthermore, studies have demonstrated increased excitability of the nociceptive pathway in
migraine sufferers, and
CGRP receptor antagonists have been shown to be efficacious in
migraine pain. Thus, such persistent neuroadaptive changes may be relevant to the processes that promote MOH.