Alpha-2 Adrenergic and Opioid Spinal Analgesic Synergy: Utility and Cellular Mechanisms
Department of Pharmacology, Paul Insel Lab
University of California, San Diego
Undergraduate Institution and Major/Degree:
University of Minnesota, BS, Neuroscience, 2002 (Psychology Minor)
Opioid and alpha2-adrenergic receptors mediate diverse physiological functions, including analgesia. Opioids are used clinically in the treatment of moderate to severe pain states, but the usefulness of this class of drugs is limited during prolonged administration because of the development of adverse side-effects such as tolerance, dependence, and addiction. Although many approaches have been investigated in attempts to overcome these problems, several reports have described enhanced opiate-mediated spinal antinociception following coadministration with low doses of alpha2AR agonists. It has also been shown experimentally that alpha2AR agonists interact synergistically with opioid agonists although the mechanisms underlying this phenomenon have yet to be characterized. The main goal of my research is to elucidate the mechanisms underlying opioid/adrenergic analgesic synergy in the spinal cord using neurochemical and electrophysiological techniques. This information may be important in managing chronic, opioid-insensitive pain because synergy-enabled decreases in drug doses may mitigate the unwanted side-effects observed clinically.
- Chris Gomez
- George Wilcox
- Carolyn Fairbanks
Courses Taken Beyond the Core Courses:
- PHCL5110 Intro Pharmacology
- PHCL5462 Neuroscience Principles of Drug Abuse
- PHCL8207 Psychopharmacology Sem
- PHM8481 Advanced Neuropharmaceutics
Graduate Level Minor:
- Society for Neuroscience, Fall 2004
- Esam El-Fakahany
- George Wilcox
- Carolyn Fairbanks
- Lucy Vulchanova
- Schuster DJ, Kitto KF, Overland AC, Messing RO, Stone LS, Fairbanks CA, Wilcox GL. Protein kinase Cε is required for spinal analgesic synergy between delta opioid and alpha-2A adrenergic receptor agonist pairs. J Neurosci. 2013 Aug 14;33(33):13538-46.
- Overland, A.C., Kitto, K.F., Chabot-Doré, A.J., Rothwell, P.E., Fairbanks, C.A., Stone, L.S., Wilcox, G.L., 2009, “Protein kinase C (PKC) mediates the synergistic interaction between agonists acting at 2-adrenergic and -opioid receptors (AR & DOP) in spinal cord,” J. Neurosci., Oct 21; 29(42): 13264-73.
- Riedl, M.S., Schnell, S.A., Overland, A.C., Chabot-Doré, A.J., Taylor, A.M., Ribeiro-da-Silva, A., Elde, R.P., Wilcox, G.L., Stone, L.S., 2009, “Coexpression of alpha 2A-adrenergic and delta-opioid receptors in substance P-containing terminals in rat dorsal horn,” J. Comp. Neurol., Apr 1;513(4):385-98.
- Stein, C., Clark, J.D., Oh, U., Vasko, M.R., Wilcox, G.L., Overland, A.C., Vanderah, T.W., Spencer, R.H., 2009, “Peripheral mechanisms of pain and analgesia,” Brain Res. Rev., Apr;60(1):90-113. Review.
- Goracke-Postle, C.J., Overland, A.C., Riedl, M.S., Stone, L.S., Fairbanks, C.A., 2007, “Potassium- and capsaicin-induced release of agmatine from spinal nerve terminals,” J. Neurochem., 102: 1738-1748.
- Goracke-Postle, C.J., Overland, A.C., Stone, L.S., Fairbanks, C.A., 2007, “Agmatine transport into spinal nerve terminals is modulated by polyamine analogs,” J. Neurochem., 100(1):132-41.
- Nguyen HO, Goracke-Postle CJ, Kaminski LL, Overland AC, Morgan AD, Fairbanks CA. Neuropharmacokinetic and dynamic studies of agmatine. Annals of the New York Academy of Sciences. 2003. 1009:82-105.
- Hiraoka, K, Trexler A., Fujioka B, Guo Z, Zhang HJ, Overland A, Oberbroeckling J, Sageshima J, Shibata S, Sutherland DER, Hering BJ. Optimal temperature in pancreas preservation by the two-layer cold storage method before islet isolation. Transplant. Proc. 2001. 33: 891-892.
- Aaron C. Overland, Laura S. Stone, Carolyn A. Fairbanks, George L.
Wilcox. Depolarization-dependent release dynamics of agmatine and D-aspartate from spinal synaptosomes: Inhibition by delta opioid receptor activation. American Pain Society Annual Meeting Abstracts. 2007.
Awards and Honors:
- 2005-present, Neuroscience Training in Drug Abuse Research, Training Grant
- American Pain Society
- Duluth, MN