The effect of neonatal capsaicin treatment on the CGRP-immunoreaction in the trigeminal subnucleus caudalis of mice

Abstract

The calcitonin-gene related peptide (CGRP) is a primary afferent neurotransmitter in the trigeminal system. Although a neonatal administration of capsaicin eliminates substance P (SP)-mediated nociceptive responses to induce a permanent functional reduction in C-fibers, little information is available regarding changes in CGRP-immunoreaction in mice undergoing neonatal capsaicin treatment (CP mice). This study examined postnatal changes in the distribution of CGRP-immunoreaction in the trigeminal subnucleus caudalis and-trigeminal ganglion of CP mice by immunohistochemical technique and a quantitative analysis. Immunohistochemistry for CGRP in the subnucleus caudalis (Vc) demonstrated two dense distributions of neurons in the CP mice as well as naïve mice: in the marginal layer and the region 400-600 μm deep. The quantitative analysis revealed no significant difference in the density of CGRP immunoreaction between naïve and CP mice 1-8 weeks of age. In the trigeminal ganglion of both groups, the size distribution of CGRP- positive neurons displayed a distribution pattern with one peak in 200-300 μm2 at week 1 and with two peaks in 200-300 μm2 and 600-700 μm2 at week 8 but no significant difference in neural density existed between these regions. When double staining in the naïve mice with CGRP or SP and VR1, a capsaicin receptor, was done, many trigeminal ganglion neurons co-expressed SP- and VR1-immunoreactions, but rarely exhibited CGRP/ VR1-co-localization. Taken together with previous data, these current observations suggest that CGRP containing afferent neurons possibly performs differing roles in nociceptive afferent input transmission within the Vc from SP-containing neurons in mice.