Variability in Capsaicin-stimulated Calcitonin Gene-related Peptide Release from Human Dental Pulp

Introduction: The unique innervation and anatomic features of dental pulp contribute to the remarkable finding that any physical stimulation of pulpal tissue is painful. Furthermore, when pathological processes such as caries affect teeth and produce inflammation of the pulp, the pain experienced can be quite intense and debilitating. To better understand these underlying neurobiological mechanisms and identify novel analgesic targets for pulpally derived pain; we have developed a powerful ex vivo model using human tooth slices. Methods: Noncarious, freshly extracted teeth were collected and sectioned longitudinally into 1 mm-thick slices containing both dental pulp and the surrounding mineralized tissues. Tooth slices from 36 patients were exposed to 60 mu mol/L capsaicin to stimulate the release of calcitonin gene-related peptide (CGRP) from nerve terminals in the pulp. Patient factors were analyzed for their effects on capsaicin-stimulated CGRP release using a mixed model analysis of variance. Results: Approximately one third of the variability observed in capsaicin-evoked CGRP release was attributable to differences between individuals. In terms of individual factors, there was no effect of anesthesia type, sex, or age on capsaicin-stimulated CGRP release. Using a within-subject study design, a significant effect of capsaicin on CGRP release was observed. Conclusions: Capsaicin-stimulated CGRP release from dental pulp is highly variable between individuals. A within subject study design improves the variability and maximizes the potential of this powerful translational model to test the efficacy of novel pharmacotherapeutic agents on human peripheral nociceptors.