CALCITONIN GENE-RELATED PEPTIDE (CGRP) is a recently discovered neuropeptide that exists in abundance in primary afferent neurons. It is located at both the primary central nervous system synapse and the specialized nerve endings of sensory nerves, being most heavily concentrated in non-myelinated C fiber endings. Two properties of CGRP are of special interest to clinicians: a) it is the most potent vasodilator identified to date and b) is believed to alter or sensitize surrounding nerves during noxious stimulation, producing a hyperalgesia. We are investigating the role of CGRP in modulating nociception after being released by sensory-efferent phenomena. To do this we have created a method that involves stimulation of the dorsal hindpaw skin of the mouse with radiant heat. After stimulation and measurement of heat nociceptive threshold, the tissue that was stimulated is removed and processed for CGRP content via radioimmunoassay. This allows us to correlate that level of CGRP (in tissue densely innervated with C-fibers) with heat noriceptive threshold. We have studied the correlation of CGRP levels and nocieptive threshold in a variety of normal and injured conditions. In addition, we are measuring the CGRP content of normal and inflamed dental pulp and comparing these findings to a number of clinical signs and symptoms. Finally, the vasodilatory effects of CGRP are being assessed in mouse skin under normal and injured conditions with laser doppler flowmetry. Taken together, these three pieces of information should help us distinguish the vaodilatory and sensitizing actions of CGRP as they relate to nociception. This research is directly applicable to my clinical training which consists of anesthesiology and the diagnosis and treatment of orafacial pain. Several chronic inflammatory conditions and vascular abnormalities cause pain through a vasodilatory mechanism. A better understanding of the actions of CGRP may contribute to the development of a CGRP antagonist to treat these disorders.
