Advances in understanding migraine for the development of novel pharmacotherapies: the use of human provocation migraine models.

Abstract

Introduction: Whilst migraine treatment has advanced significantly over recent times, the mechanisms of attack genesis and heterogeneity in treatment response are two amidst several areas that remain poorly understood and require further development. Experimental migraine provocation is an area that holds promise in advancing this understanding.

Areas covered: We conducted a literature search using PubMed, of 'human migraine triggering' and 'human migraine provocation' to identify articles of interest. We discuss therapeutic targets that have emerged from such work, including calcitonin family peptides (amylin (AMY) and adrenomedullin (ADM)), pituitary adenylate cyclase-activating peptide (PACAP) and potassium channels. We discuss our views on the clinical translation of the outcomes of such studies, and their previous and potential future impact on migraine therapeutics.

Expert opinion: Migraine provocation models provide a valuable means to study human migraine phenotypically and biologically, as well as to assess treatment response. Downstream intracellular mechanisms of provocation agents can be targeted during cellular processing to alter cell function and influence migraine mechanisms. It is important to caveat the clinical translation of provocation studies, given that just because a substance triggers migraine experimentally, does not necessarily mean that the substance is involved in the spontaneous human condition.