Figure 6.

Connections between p-ERK, CGRP and COX-2 in the pathophysi-ological mechanisms of migraine. Electrical stimulation of the TG leads to neurogenic inflammation in trigeminal neurons and glial cells followed by mast cell degranulation. Mast cell degranulation in turn activates mast cells to release COX-2 followed by synthesis of PGE₂. Newly synthesized PGE₂ induces trigeminal neurons to release CGRP and also induces TRPV1 sensitization. The influx of Ca²⁺ via TRPV1 upregulates the level of p-ERK in the TG and causes peripheral and central hypersensitivity, which induces migraine attack and pain. p-ERK, phosphorylated extracellular signal-regulated kinase; CGRP, calcitonin gene-related peptide; COX-2, cyclooxygenase-2; TRPV1, transient receptor potential vanilloid receptor 1; TG, trigeminal ganglion; PGE₂, prostaglandin E₂.