miR‐34a‐5p up‐regulates the IL‐1β/COX2/PGE2 inflammation pathway and induces the release of CGRP via inhibition of SIRT1 in rat trigeminal ganglion neurons

Migraine is a debilitating neurological condition, with a global prevalence rate of 10.68% in men and 18.79% in women. Elucidation of the molecular mechanisms underlying migraines is of great importance for improving the quality of life of patients. The release of the neuropeptide calcitonin gene‐related peptide (CGRP) from trigeminal nerve terminals is involved in the pathogenesis of migraine. Recent studies have shown that up‐regulation of miR‐34a‐5p expression is associated with acute migraine attacks. Here, we investigated whether alteration of the expression of miR‐34a‐5p induces the release of the vasoactive peptide CGRP. We isolated primary rat trigeminal ganglion neurons and performed gain‐ and loss‐of‐function assays to alter the expression level of miR‐34a‐5p. Down‐regulation of miR‐34a‐5p inhibited the expression of interleukin‐1β (IL‐1β)/cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2), decreased IL‐1β, PGE2 and CGRP release, and up‐regulated the expression of silencing information regulator 1 (SIRT1) in trigeminal ganglion, whereas overexpression of miR‐34a‐5p enhanced the expression of IL‐1β/COX2/PGE2, increased the release of IL‐1β, PGE2 and CGRP, and decreased the expression of SIRT1 in trigeminal ganglion. In addition, overexpression of miR‐34a‐5p induced apoptosis in primary rat trigeminal neurons. In summary, these findings suggest that miR‐34a‐5p up‐regulates the IL‐1β/COX2/PGE2 inflammation pathway, induces apoptosis and enhances release of CGRP via inhibition of SIRT1 expression in trigeminal ganglion neurons; thus, miR‐34a‐5p may have potential as a therapeutic target for the treatment of migraine.