Pilot Projects

Congratulations to our 2013 Pilot Grant Recipients

Tamara King, Ph.D.

 Assistant Professor of Biomedical Sciences, College of Osteopathic Medicine. View bio

Project Title: 

Peripheral Mechanisms of Ongoing Osteoarthritis Pain

Project Summary:

Dr. King’s pilot project explores osteoarthritis (OA) pain, a condition affecting nearly a third of the U.S. population over 65. Though OA pain is predominantly treated with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), for many patients, NSAIDs become ineffective and joint replacement is used as a last resort. Understanding the mechanisms giving rise to this chronic, NSAID-resistant pain is important for improving therapies. However, the lack of preclinical animal models has posed a major setback. In the proposed studies, Dr. King examines a rat model of advanced OA pain that is both ongoing and NSAID-resistant. She hypothesizes that this advanced OA pain represents a neuropathic pain state in which changes in nerve structure and function at the periphery have led to central sensitization. To test this hypothesis, Dr. King will work closely with the Histology and Imaging Core using immunohistochemistry to study the structure and molecular composition of afferent fibers innervating the affected bone. She will also work with the behavior core, implementing a variety of behavioral assays, including conditioned place preference to pain relief, a test of motivated behavior, to monitor pain in this animal model.

John Streicher, Ph.D. 

Assistant Professor of Biomedical Sciences, College of Osteopathic Medicine. View bio

Project Title: 

Identification of the Activated Signaling Complex of the Mu Opioid Receptor

Project Summary: 

Dr. Streicher’s pilot project aims to discover better treatments for chronic pain by expanding our current understanding of the mu opioid receptor protein complex and how it functions before and after drug activation. Currently, the major treatment for chronic pain is opioid drugs, and while these drugs can provide effective pain relief, their efficacy is limited by negative side effects including constipation, tolerance, dependence, and addiction. Investigation into the receptor for these drugs, the mu opioid receptor, reveals that different downstream signaling pathways mediate different actions of the drugs. For instance, beta-arrestin2 is downstream of the mu opioid receptor and signaling through this pathway inhibits the anti-nociceptive action of opioids while promoting the negative side effects. Thus, designing opioids that are biased against beta-arrestin2 signaling can dramatically improve their side effect profile. This ability of specific drugs to preferentially activate one downstream signaling pathway over another at a given receptor is called functional selectivity and it represents a powerful tool for designing drugs with improved efficacy and fewer unwanted side effects. Yet, to fully capitalize on this potential, a complete characterization of the downstream pathways  and their output is necessary for the mu opioid receptor. Using immunoprecipitation and mass spectrometry, Dr. Streicher aims to identify the full complement of proteins comprising the mu opioid receptor complex and to characterize their downstream pathways in order to determine which pathways are best to target for future drug design and improved pain therapy.