Pregnancy increases perivascular trigeminal innervation of cerebral arteries without changing reactivity to calcitonin gene‐related peptide (CGRP)

Abstract

This study investigated the influence of pregnancy and postpartum on trigeminal innervation of posterior cerebral arteries (PCA) and reactivity to CGRP. Third-order PCAs were dissected from nonpregnant (NP, n=35), late-pregnant (LP, day 19–20, n=32), or postpartum (PP, day 3–4, n=32) Sprague Dawley rats and either fixed for immunohistochemical staining of CGRP-reactive nerve fibers or mounted in an arteriograph chamber for concentration-response curves to CGRP (0.1–300nM). Nerve density was determined by Metamorph analysis as intersect points on a grid per area after confocal imaging. Pregnancy had a trophic influence on perivascular CGRP-containing nerve fibers, increasing nerve density from 0.6 ± 0.2 counts/μm2 in NP to 1.3 ± 0.3 counts/μm2 in LP (p<0.01). Nerve density significantly decreased in PP animals to 0.2 ± 0.1 counts/μm2 (p<0.01 vs. LP). The gestation-induced increase in CGRP innervation was not accompanied by a change in reactivity. Percent dilation from spontaneous tone at 300nM CGRP for NP, LP and PP animals was: 70±7%, 69±12% and 74±10% (p>0.05). These results demonstrate that trigeminal innervation of PCAs is increased during gestation that is not accompanied by changes in reactivity. It is possible that increased CGRP nerve density during pregnancy relates more to nociception and a predisposition to the neurologic symptoms of eclampsia than to changes in blood flow. Supported by RO1 NS045940 and AHA 0540081N.