The processes underlying chronic migraine pathophysiology and its treatment with botulinum toxin type A

Abstract

AbstractObjectiveTo comprehensively review both the models of migraine pathophysiology and transformation to chronic migraine, and align these with the known effects of botulinum toxin type A (BTX‐A).BackgroundMigraine is a relatively common, disabling, and debilitating condition that is notoriously difficult to manage by pain specialists. A comprehensive review of the mechanisms of its pathophysiology, chronification, and treatment with BTX‐A is lacking.MethodsThis narrative literature review is formed following an intensive search of scientific literature on PubMed, CENTRAL, and EMBASE databases using relevant key search terms.ResultsMigraine can be seen as a threshold disorder with multiple mechanisms: hyperexcitability of trigeminal afferents, impaired descending inhibition, and central sensitization. The mechanism of transformation to chronic migraine, where headache symptoms occur on at least 15 days per month, remains unclear, but key risk factors include sex (female), headache frequency, psychiatric co‐morbidities, obesity, and low socioeconomic status. Botulinum toxin A is an exotoxin produced by the gram‐positive rod bacterium Clostridium botulinum. Following the agent's initial use in aesthetic medicine, it is now an FDA‐approved treatment for chronic migraine. The toxin has multiple modes of action in chronic migraine, including neurotransmitter exocytosis blockade, inhibition of membrane receptor insertion, and anti‐inflammatory processes.ConclusionMigraine is likely caused by intrinsic hyperexcitability of the trigeminovascular nociceptive system, disrupted descending inhibitory pain networks, and central sensitization. Pathophysiology of chronification is poorly understood. BTX‐A acts primarily by attenuating neuropeptidergic signaling, inhibiting membrane receptor insertion, and downregulating expression of receptors implicated in cortical spreading depression.