A progressive series of studies is proposed which will: 1) develop and refine a new animal model of pain; 2) define specific guidelines for the management of clinical pain in animals; and 3) provide a deeper understanding of the role played by endogenous opioid systems (EOS) in the modulation of pain in both animals and humans. In the initial studies, the cortical evoked potential (CEP) associated with electrical stimulation of the tooth pulp will be evaluated as a sensitive, specific, and reliable indicator of pain and analgesia in laboratory rats. Preliminary data from this laboratory strongly suggest that, as in humans and other animals, the magnitude of the CEP in rats is correlated with both stimulus intensity and pain perception. The value of the rat CEP model will be explored in a study comparing the efficacies of several analgesic drugs, most of which are already used in the treatment of clinical pain. Then, during the final 2 year of the award, the rat CEP model will be used to study the participation of EOS in natural mechanisms of pain and analgesia. Initially, radioimmunoassay techniques will be used to measure basal levels of representative opioid peptides in rat plasma. Subsequent studies will explore circumstantial and causal associations between experimental pain and several opioid peptides. These data should also provide preliminary indications as to which opioid receptor subtype(s) is (are) most important in modulating pain. Over the course of this 5-year project, the candidate will gain expertise and sharpen research skills necessary to continue a career of independent research into the physiological and biochemical basis of pain and analgesia. Her first research efforts in this area resulted in a master of science degree and a published evaluation of the analgesic efficacy of, and role of EOS in, the immobility response in rabbits. The candidate's mentor has considerable expertise in the scientific investigation of EOS, with numerous publications and several ongoing grants in this area. Other investigators with expertise in the fields of neurophysiology, pharmacology, and pain have contributed to the collection of preliminary data and will continue to function as consultants for this project. The research will be carried out in a well-equipped laboratory with ready access to support services and extensive medical and general libraries.
