Calcitonin Gene-Related Peptide Promotes Peripheral and Central Trigeminal Sensitization

Temporomandibular joint disorder is characterized by peripheral and central sensitization of trigeminal nociceptive neurons. Although CGRP is implicated in the development of central sensitization by stimulating glial activation via its receptor, the mechanism by which CGRP promotes and maintains sensitization of trigeminal nociceptive neurons is not well understood. The goal of my study was to investigate the role of calcitonin gene-related peptide (CGRP) on the initiation and maintenance of a nocifensive withdrawal response to mechanical stimulation following activation of primary trigeminal sensory neurons. For my studies, I used adult male Sprague Dawley rats that were injected with CGRP alone or co-injected with inhibitors and determined changes in nocifensive behavior and inflammatory proteins. Intrathecal injection of CGRP increased nocifensive responses to mechanical stimulation up to 48 hours and this stimulatory effect was blocked by the antagonist peptide CGRP8-37 and a protein kinase A inhibitor. Results from my cellular studies provide evidence that elevated levels of CGRP in the spinal cord can promote bidirectional signaling within the trigeminal system, a novel finding that helps to explain how central sensitization can lower the activation threshold of primary nociceptors in TMD patients