Neural Plasticity in Migraine Chronification

Abstract

Chronic migraine (CM) is the ultimate and most burdensome form of the transformation from episodic migraine (EM), called chronification. The mechanism behind migraine chronification is poorly known and difficult to explore as CM has the same spectrum of pathogenesis as EM and the EM-CM transition is bidirectional. Central sensitization (CS) is a key phenomenon in migraine: its mechanisms include disturbed neural plasticity, which is the ability of the nervous system to adapt to endo- and exogenous changes. Cutaneous allodynia, a maker of central sensitization, may be an easy-to-determine marker of the EM-CM transition. Pituitary adenylate cyclase-activating peptide, a pro-inflammatory, vasodilatory and pain-producing neuropeptide, which has been proposed as an alternative to CGRP target in migraine, was shown to improve CS by regulating synaptic plasticity in the trigeminal nucleus caudalis in CM rats. Oxytocin and its receptor were found to influence CS through modulating synaptic plasticity in CM mice. Similar results were obtained for ephrin type-B receptor and its ligands. These and other studies suggest that neural plasticity may be important in CM pathogenesis. Still, its involvement in migraine chronification requires further studies which should include patients/animals with EM and CM. In this narrative/hypothesis paper, we review the current literature on the molecular mechanisms of CM pathogenesis and try to link them with neural plasticity and central sensitization to support the hypothesis that it is a key element in migraine chronification.