Abstract
Introduction: Migraine is a common neurological disease and is listed second among the most disabling health conditions worldwide. Refractory migraine (RM) is a term used to emphasize the unresponsiveness of migraine to various treatment options, encompassing both episodic refractory and chronic refractory migraine. In this paper we discuss various known and possible mechanisms of pharmacological refractoriness in RM, such as possible involvement of the gut microbiome, the blood-brain barrier, migraine genetics and various mechanisms of pharmacokinetic and pharmacodynamic tolerance. Development of medication-overuse headache as a secondary disorder following migraine is also considered. We argue that the available literature is insufficient to fully explain the mechanisms of refractoriness and we present our hypothesis.
NSTL
Elsevier