1522 M2 Muscarinic Agonists Inhibit Capsaicin-Sensitive Neurons in Peripheral Human Tissues
E. TREVINO, C. HUYNH, E. LOCKE, X. SUN, K. KEISER, and K. HARGREAVES, University of Texas - San Antonio / Health Science Ctr, USA

Muscarinic acetycholine receptors are widely expressed throughout the central and peripheral nervous systems, and are involved in many important physiological processes. Previous data collected from animals have shown that activation of peripheral muscarinic M2 receptors produces antinociception in vivo and the inhibition of nociceptor activity in vitro Objectives: In the present study, we evaluated the hypothesis that the selective muscarinic receptor agonist arecaidine inhibits neurosecretion of immunoreactive substance P (iSP) from isolated human nociceptors. Methods: The isolated sensory terminals were contained in clinical biopsies of periradicular connective tissues attached to the roots of extracted human teeth. Patients signed an IRB approved informed consent and teeth were extracted under local anesthesia. The apical 6mm segment of the root was resected and placed in a modified oxygenated Locke Ringers buffer, with collection of samples every 20 min. Released immunoreactive SP (iSP) was measured by enzyme-linked immunosorbent assay (ELISA), and the data were analyzed by 2 sample t-test. Test drugs did not interfere with the ELISA. Results: Application of a solution of 50uM capsaicin produced a 160% increase in iSP release over baseline levels. Pre-treatment with 1uM arecaidine significantly (p=0.001) inhibited capsaicin-evoked iSP release. Conclusions: These results indicate that muscarinics inhibit iSP release from terminals in isolated human biopsies. This method may have utility in evaluating the pharmacodynamics of peripheral muscarinics in peripheral human tissue. This work was supported by NIDCR T-32 DE14318 and NIH RO1 DA10510-0

Seq #187 - Orofacial Pain Mechanisms
10:45 AM-12:45 PM, Friday, 11 March 2005 Baltimore Convention Center 331

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