? The applicant is a veterinary surgeon with a long-standing interest in pain research and is applying for a Research Career Development Award (K). During the course of caring for client-owned pets (companion dogs) that present daily to the University of Pennsylvania Veterinary Hospital, she developed the idea that companion dogs with spontaneous chronic painful conditions have the potential to serve as preclinical models for human clinical pain research. This led to her desire to change her focus from clinical veterinary practice to pursuing a career as an independent clinician-scientist active in translational pain research. Therefore, this application involves both formal training and a mentor relationship in Clinical Epidemiology and Outcomes Research, leading to a Masters of Science in Clinical Epidemiology (MSCE) and through the design and implementation of two companion animal clinical trials the experience necessary to develop into a truly effective translational pain researcher. The candidate's mentor, Dr John Farrar is a neurologist and a senior scholar in the Center for Clinical Epidemiology and Biostatistics (CCEB), whose primary activity is NIH and other funded research in clinical pain management. Along with the other co-investigators, his expertise is in study design methodology including the evaluation of pain, the impact of therapeutic interventions and the development of measurement tools to assess the effects of those interventions. Since the primary limitation to the use of a companion dog model is the lack of validated assessment tools for chronic pain in dogs, this proposal involves: 1) the validation of human caregiver observation assessment tools (recently developed by the PI) in the well-validated canine osteoarthritis model of chronic pain; and 2) the use of those tools to demonstrate the efficacy of a novel, single intrathecal injection analgesic (resiniferatoxin) in companion dogs presenting with osteosarcoma. Osteosarcoma is a common spontaneous bone tumor in dogs that is histologically indistinguishable with and has a progression of disease closely mirroring the disease in humans. Pilot data suggests that this companion animal canine osteosarcoma (CACO) model of pain will help bridge the information gap between the induced rodent models of cancer pain and human clinical cancer pain research. It will provide insights into the treatment of human bone cancer pain through the testing of novel therapies. In addition, this proposal will generate the tools necessary to perform a multitude of outcome based research studies using companion dogs as a preclinical model and at the same time provide the training and experience necessary for the PI to develop a successful career as an independent investigator in translational pain research. ? ? ? ?
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