Pathophysiology of medication overuse headache: insights and hypotheses from preclinical studies

Abstract

Introduction: Medication overuse headache (MOH) is a clinical concern in the management of migraine headache. MOH arises from the frequent use of medications used for the treatment of a primary headache. Medications that can cause MOH include opioid analgesics as well as formulations designed for the treatment of migraine, such as triptans, ergot alkaloids, or drug combinations that include caffeine and barbiturates.

Literature review: Gathering evidence indicates that migraine patients are more susceptible to development of MOH, and that prolonged use of these medications increases the prognosis for development of chronic migraine, leading to the suggestion that similar underlying mechanisms may drive both migraine headache and MOH. In this review, we examine the link between several mechanisms that have been linked to migraine headache and a potential role in MOH. For example, cortical spreading depression (CSD), associated with migraine development, is increased in frequency with prolonged use of topiramate or paracetamol.

Conclusions: Increased CGRP levels in the blood have been linked to migraine and elevated CGRP can be casued by prolonged sumatriptan exposure. Possible mechanisms that may be common to both migraine and MOH include increased endogenous facilitation of pain and/or diminished diminished endogenous pain inhibition. Neuroanatomical pathways mediating these effects are examined.

Figure 1

Schematic diagram illustrating the interaction of descending projections involved in the inhibition and facilitation of pain. Placement of the rat’s tail in hot water activates dorsal horn nociceptive neurons that project to the subnucleus reticularis dorsalis (SRD). Descending projections from the SRD inhibit nociceptive transmission produced by the activation of dural afferents. In addition, noxious tail stimulation activates pain-facilitating neurons in the rostral ventromedial medulla (RVM), mainly through indirect projections. Evidence indicates a shift in the balance between these two systems following chronic morphine exposure, such that descending facilitation dominates, masking DNIC.