An underrepresented majority: A systematic review utilizing allodynic criteria to examine the present scarcity of discrete animal models for episodic migraine.

Abstract

Despite increasing evidence differentiating episodic and chronic migraine, little work has determined how currently utilized animal models of migraine best represent each distinct disease state. In this review, we seek to characterize accepted preclinical models of migraine-like headache by their ability to recapitulate the clinical allodynic features of either episodic or chronic migraine. From a search of the Pu bMed database for "animal models of migraine", "headache models" and "preclinical migraine", we identified approximately 80 recent (within the past 20 years) publications that utilized one of 10 different models for migraine research. Models reviewed fit into one of the following categories: Dural KCl application, direct electrical stimulation, nitroglycerin administration, inflammatory soup injection, CGRP injection, medication overuse, monogenic animals, post-traumatic headache, specific channel activation, and hormone manipulation. Recapitulation of clinical features including cephalic and extracephalic hypersensitivity were evaluated for each and compared. Episodic migraineurs comprise over half of the migraine population, yet the vast majority of current animal models of migraine appear to best represent chronic migraine states. While some of these models can be modified to reflect episodic migraine, there remains a need for non-invasive, validated models of episodic migraine to enhance the clinical translation of migraine research.