Differential Regulation of Calcitonin Gene-Related Peptide Secretion from Trigeminal Ganglion Neurons by Carbon Dioxide

Carrie Vause

Date of Graduation

Fall 2006

Degree

Master of Science in Biology

Department

Biology

Committee Chair

Paul Durham

Abstract

The neuropeptide calcitonin gene-related peptide (CGRP) is implicated in the pathophysiology of migraine and rhinitis. Recent clinical evidence supports the use of non-inhaled intranasal delivery of 100% carbon dioxide (CO2) for treatment of these conditions. Patients treated with CO2 report two distinct physiological events: first, a short duration stinging or burning sensation within the nose, and secondly, alleviation of primary symptoms. The goal of this study was to determine whether the physiological effects of CO2 involve regulation of CGRP secretion from trigeminal sensory neurons. I hypothesize that the anti-nociceptive effects of CO2 treatment involve the inhibition of CGRP release from trigeminal neurons via changes in intracellular pH and suppression of ion channel activity. Initially, incubation of primary trigeminal ganglia cultures at pH 5.0 or 5.5 was shown to significantly stimulate CGRP release. Similarly, exposure of cultures to 100% CO2 caused a time-dependent acidification of the media, achieving pH values of 5.5 – 6.0 that stimulated CGRP secretion. In addition, KCl, capsaicin, and nitric oxide donor also caused a significant increase in CGRP release. Interestingly, Co2 treatment of cultures under isohydric conditions, which prevents extracellular acidification while allowing changes in PCO2, significantly repressed the stimulatory effects of KCL, capsaicin, and nitric oxide in intracellular calcium. Results from this study provide the first evidence of a unique regulatory mechanism by which CO2 inhibits sensory nerve activation, and subsequent neuropeptide release. Furthermore, my data are suggestive that the suppressive effect of Co2 involves a decrease in intracellular pH and inhibition of high voltage-gated calcium channels.

Keywords

trigeminal, migraine, calcium, protons, CGRP

Subject Categories

Biology

Copyright

© Carrie Vause

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Dissertation/Thesis

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