Regulation of CGRP Expression in an in Vivo Model of Temporomandibular Joint Inflammation

Vinit Patil

Date of Graduation

Fall 2006

Degree

Master of Science in Biology

Department

Biology

Committee Chair

Paul Durham

Abstract

Peripheral release of calcitonin gene-related peptide (CGRP) from sensory trigeminal ganglion neurons contributes to neurogenic inflammation within the temporomandibular joint (TMJ) and central release of CGRP mediates pain and central sensitization. The goal of this study was to determine the effects of inflammatory and anti-inflammatory agents on CGRP levels within trigeminal ganglion. Initially, neurons innervating the TMJ were localized within the ganglion by retrograde labeling using True Blue. Next, immunohistochemistry was used to identify CGRP and transit receptor potential vanilloid type 1 (TRPV1) expressing neurons within the entire trigeminal ganglion vanilloid type 1 (TRPV1) expressing neurons within the entire trigeminal ganglion. Almost all CGRP containing neuronal cells (>90%) also expressed TRPV1, a marker of sensory C-fibers that mediate pain transmission. Injection of capsaicin, a TRPV1 agonist, caused an ipsilateral decrease in CGRP levels in the posterior third of the ganglion after 2 hr. This decrease was attenuated by overnight pretreatment with a concentrated cocoa bean extract, enriched in polyphenolic compounds. Injection of the nitric oxide (NO) donor SNP at pH 5.5 caused an ipsilateral increase in CGRP levels after 24 hr that was blocked by pretreatment with polyphenolic compound catechin. In addition, Overnight treatment with SB 203580 repressed NO/proton stimulation at 24 hr. In conclusion, data from our study supports the use of this in vivo model to more thoroughly investigate the cellular and the molecular mechanisms that control CGRP synthesis and release from trigeminal ganglion neurons under normal, pathological, and therapeutic conditions.

Keywords

CGRP, TRPV1, TMJ, temporomandibular joint disease, true blue, retrograde labeling, trigeminal ganglion

Subject Categories

Biology

Copyright

© Vinit Patil

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Dissertation/Thesis

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