This is a request for a Scientist Development Award for Clinicians (K2O) which will allow me to focus full-time on my basic research interest, developing new skills in molecular biology. The present research proposal outlines a strategy to develop and behaviorally and biochemically characterize a new model of mixed somatic/neuropathic pain that will allow the discovery of new non-opioid pain relievers that will both improve the management of cancer pain and the treatment of drug abuse. This new model will be developed in the BALB/c mice with sarcomatous compression of the sciatic nerve producing a behavioral hyperalgesia. This new model will be behaviorally characterized with the use of N-methyl-D-aspartate receptor antagonists, nitric oxide synthase (NOS) inhibitors and calcium channel antagonists for their ability to prevent behavioral hyperalgesia in this new model and compared with, modified ligation model, and the formalin model of somatic pain. Further biochemical characterization of these three models of hyperalgesia will be undertaken with the use of marker genes and antisense knockouts as a potential new therapy for hyperalgesia. Once these three models of hyperalgesia are behaviorally and biochemically characterized, they will be utilized to develop new models of opioid tolerance and dependence. This K2O grant will contribute profoundly to my career development as a future clinician/scientist by providing me with the opportunity to pursue full-time training in molecular biology and with the provision of salary support and supplies to undertake the studies outlined in this proposal.
