Research Article: PACAP signaling is not involved in GTN- and levcromakalim-induced hypersensitivity in mouse models of migraine
Abstract:
Calcitonin gene-related peptide (CGRP) antagonizing drugs represents the most important advance in migraine therapy for decades. However, these new drugs are only effective in 50–60% of patients. Recent studies have shown that the pituitary adenylate cyclase-activating peptide (PACAP38) pathway is independent from the CGRP signaling pathway. Here, we investigate PACAP38 signaling pathways in relation to glyceryl trinitrate (GTN), levcromakalim and sumatriptan.
Introduction:
Over the past 20 years two endogenous neuropeptides, calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide (PACAP) have been of increasing interest in migraine [1]. The development and introduction of drugs targeting CGRP or its receptors represent the most important advances in migraine therapy for decades [2]. However, CGRP signaling pathway targeted therapies are effective only in 50–60% of patients [3,4,5,6]. The mechanisms in 40% of the patients who do not respond to CGRP…
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