The objectives of this project are 1) to evaluate the neuroendocrine responses to surgical stress and inflammation, 2) to determine the analgesic and anti-inflammatory effects of prototype and novel drugs which alter either the synthesis or the receptor activation of neuroendocrine mediators, and 3) to evaluate the clinical utility of these novel drugs in controlled clinical trials. Previous work on the physiologic function of plasma beta-endorphin and regulation of its release has provided evidence of enhanced release by a variety of stressors, including clinical pain following oral surgery. A recent study attempted to extend this line of investigation to evaluate the relationship between endorphin release and chest pain in patients with coronary artery disease. Plasma levels of beta-endorphin were measured at rest, at the peak of treadmill exercise, and following 10 minutes recovery in 46 patients with chest pain and normal coronaries, with coronary artery disease, and in volunteers with normal coronary arteries and no chest pain. A significant increase in beta- endorphin levels were seen over time but not between groups. Greatest levels were seen during recovery but did differ significantly between patients with chest pain and normal coronary arteries, patients with coronary artery disease, or normals. These data are consistent with previous observations that exercise stress is a sufficient stimulus for the release of pituitary beta-endorphin. The lack of differences between the three groups, however, does not provide any support for the hypothesis that a deficient release of endorphin during exercise occurs in patients with chest pain and normal coronary arteries. Rather the data demonstrate that the magnitude of endorphin release is secondary to the duration of the exercise stress, suggesting that endorphin release in these patient groups in response to physical exercise and associated pain is similar to normals. Increasing evidence suggests that the nociceptive afferent barrage which can occur during a surgical procedure can activate central processes leading to an increased perception of clinical pain long after the nociceptive input is removed. This hypothesis is being evaluated in the oral surgery model by randomly allocating local anesthesia or placebo anesthesia prior to the surgical removal of third molars with general anesthesia. Demonstration of a difference between groups at 24 and 48 hours, long after the local anesthetic has dissipated, will provide evidence to support the hypothesis that nociceptive afferent barrage produces central plasticity leading to increased postoperative pain.
