Fig. 3
From: Hypersensitivity to BKCa channel opening in persistent post-traumatic headache

Possible Mechanisms and Sites of Action of Migraine-Like Headache induced by BKCa Channel Opening in Persons with PPTH. The figure outlines a proposed mechanism and site of action though which opening of BKCa channels contributes to the development of migraine-like headache in persons with PPTH. In this suggested model, the signaling molecules CGRP and PACAP-38 bind to their respective G protein-coupled receptors present on the vascular smooth muscle cells of intracranial arteries. This initiates the activation of cAMP-dependent signaling pathways, which then results in opening of BKCa channels. The subsequent release of potassium ions and accompanying vasodilation leads to activation and sensitization of perivascular meningeal nociceptors, a process facilitated by both chemical and mechanical stimulation. Modified from Al-Khazali et al., 2023 [21]. CGRP = calcitonin gene-related peptide; PACAP-38 = pituitary adenylate cyclase-activating polypeptide-38; AC = adenylate cyclase; ATP = adenosine triphosphate; cAMP = cyclic adenosine monophosphate; BKCa channels = large conductance calcium-activated potassium channels