2014 Pilot Grant Recipients
Glenn Stevenson, Ph.D.
Associate Professor, College of Arts and Sciences.
Tamara King, Ph.D.
Associate Professor of Biomedical Sciences, College of Osteopathic Medicine. View bio
Characterization of Delta/Mu Opioid Receptor Interactions on Chronic Osteoarthritis Pain-depressed Behaviors
In their study, Dr. Stevenson and Dr. King are looking to develop safer and more effective ways to treat osteoarthritis pain with delta and mu opioid receptor agonists. Currently, mu opioid receptor agnosits are among the frontline treatments for chronic pain; however, these medications have a number of negative side effects, including bone fractures and bone loss. According to experimental evidence on delta/mu opioid receptor interactions, the addition of delta agonists enhances the anti-nociceptive effects of mu agonists while not attenuating undesirable side effects. Therefore, exploiting these interactions could produce enhanced pain relief without negatively influencing bone pathology. Since the effects of delta/ mu agonists have been studied in acute pain, Drs. Stevenson and King plan to look at the effectiveness of this treatment in a model of chronic pain (osteoarthritis) to determine if delta/mu agonist mixtures will provide optimal pain relief. These studies will utilize the Histology and Imaging Core facilities to evaluate the effect of delta and mu receptor agonist treatment on bone and joint pathology in rats.
John Streicher, Ph.D.
Assistant Professor of Biomedical Sciences, College of Osteopathic Medicine. View bio
Identification of the Activated Signaling Complex of the Mu Opioid Receptor
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.