Sex differences in neuropeptide content and release from rat dental pulp

Introduction: Studies to examine sex differences in response to pain have suggested that females exhibit lower threshold responses to painful stimuli and that threshold response varies greatly at different stages of the menstrual cycle. Additional studies suggest that sex differences may be caused by societal sex roles or differences in anxiety responses by men and women. Objective: The purpose of this study was to evaluate biologically evident sex differences in male and female rats chronically treated with a systemic algogen, the nerve growth factor (NGF), by measuring neuropeptides (calcitonin gene-related peptide) content and release from isolated dental pulp. Methods: Rats were injected subcutaneously every other day with either murine NGF (1 mg/kg) or vehicle for 7 or 13 days. Isolated incisor pulp tissue was evaluated from these male and female rats (n = 96). Capsaicin-evoked neurosecretion of CGRP and tissue content were measured using a previously validated radioimmunoassay. Results: Dental pulp from female rats at 7 days showed significantly increased capsaicin-evoked immunoreactive CGRP release (>50% increase) compared with tissue from male rats. After 13 days, this release was significantly increased only in NGF-treated female rats (3-fold increase) when compared with control females or both male groups. The CGRP content in tissue from both female groups was also significantly increased after 7 days of treatment (>3 fold), but after 13 days this content was only significantly increased in tissue from NGF-treated female rats (P =.0001). Conclusions: These data suggest that sex differences affect the role of NGF in the modulation of inflammation through the regulation of peripheral neuropeptide release and content.