Neurobiology of Pain and Cognition: Edward Bilsky, Ph.D.

Research Interests

bilskyProf. Bilsky’s laboratory is focused primarily on opioid pharmacology, and how it relates to chronic pain and drug addiction. By understanding the molecular and neurochemical mechanisms of these disease states, more effective pharmacological treatments can presumably be developed.

The research involves close collaborations with medicinal chemists, molecular biologists and pharmaceutical companies to design and test novel pharmacological agents. Recent work has included synthesis and evaluation of opioid glycopeptides that produce analgesia equivalent to morphine, with decreased side-effects related to addiction liability, respiratory depression and constipation.

A second project is investigating the role of basal signaling at the mu opioid receptor. This signaling plays an important role in opioid tolerance and physical dependence. Compounds termed neutral antagonists may offer clinical advantages over naloxone (Narcan) and naltrexone (Revia) for the treatment of heroin overdose and addiction, and in the management of constipation in chronic pain patients.

The laboratory is also investigating the genetic and molecular factors that may predispose individuals to addiction, through the use of quantitative trait loci mapping techniques. The most recent research is looking at the role of pro-dynorphin gene expression in age-related cognitive dysfunction and the use of antidepressants as cognitive enhancers.

Current Laboratory Positions and Professional Training Opportunities

Prof. Bilsky’s laboratory currently employees three permanent/full-time personnel (including Maine residents and graduates of UNE). There are typically two medical and four undergraduate students conducting research each year. The skills acquired in the research laboratory are similar to those needed in the biotech and pharmaceutical industries.

Research Grants

• Glycopeptides as Analgesics: Non-Toxic Alternatives to Morphine for Combat Casualty Care, Office of Naval Research, ONR-NRD-255 Bilsky (Co-PI). The primary goal of this project is to develop and characterize opioid glyco- and glycolipopeptides in an effort to increase CNS bioavailability of opioid analgesics. It is hypothesized that these compounds will have superior analgesic and side-effect profiles compared to morphine.
   
• Novel Non-Peptide Ligands for the Opioid Receptors, National Institute on Drug Abuse/NIH, 2 R01 DA08883-04A1 Ananthan (PI). The primary goal of this project is to develop and characterize nonpeptidic mixed mu agonists/delta antagonists. It is hypothesized that these compounds will produce less tolerance and physical dependence compared to a mu agonist.
   
• Effects of Systemic Secretin Administration on Mouse Leaning and Memory, Repligen Corporation, Waltham, MA, 02453, Bilsky (PI). The goals of the research are to assess the effects of the peptide secretin on learning and memory performance in inbred strains of mice.
   
• Cognitive Enhancing Actions of Milnacipran in Mice, Cypress Bioscience Inc., San Diego, CA92121, Bilsky (PI). The primary goal of this project is to test a series of antidepressants that differ in terms of their selectivity toward norepinephrine and serotonin transporters in models of depression, locomotor activity and memory and learning tasks. The study is assessing potential strain differences in response to these drug effects.
   
• ASPET Summer Undergraduate Research Fellowship, American Society for Pharmacology and Experimental Therapeutics, Bethesda, MD 20814, Bilsky (PI). The purpose of this grant is to support undergraduate research and interest in the pharmacological science by offering student summer research fellowships.
   
• AFPE Undergraduate Research Fellowship, American Foundation for Pharmaceutical Education, Bilsky (PI), The purpose of this grant is to support an undergraduate research fellow in the PIs laboratory.
   
• Pfizer Visiting Professorship Program in Pain Medicine, Pfizer Inc., Bilsky (PI), The purpose of this foundation grant is to bring in a leader in the pain medicine field to meet with physicians and basic science researchers that are part of the pain management and research group at the University of New England.


Recent Publications

• Ananthan, S., Khare, N.K., Saini, S.K., Seitz, L.E., Bartlett, J.L., Davis, P., Dersch, C.M., Porreca, F., Rothman, R.B. and Bilsky, E.J. Identification of Opioid Ligands Possessing Mixed Mu Agonist/Delta Antagonist Activity Among Pyridomorphinans Derived from Naloxone, Oxymorphone, and Hydropmorphone. Journal of Medicinal Chemistry, 47: 1400-1412, 2004.
   
• Wang, D., Raehal, K.M., Lin, E.T., Lowery, J.J., Kieffer, B.L., Bilsky, E.J. and Sadée, W. Basal Signaling Activity of Mu Opioid Receptor in Mouse Brain: Role in Narcotic Dependence. Journal of Pharmacology and Experimental Therapeutics, 308: 512-520, 2004 (e-pub 11/2003).
   
• Wang, D., Raehal, K.M., Bilsky, E.J. and Sadée, W. Inverse agonists and neutral antagonists at mu opioid receptor (MOR): Possible role of basal receptor signaling in narcotic dependence. Journal of Neurochemistry, 77: 1590-1600, 2001.
   
• Bilsky, E.J., Egleton, R.D., Huber, J.D., Jones, H., Yamamura, H.I., Janders, J., Davis, T.P., Davis, P., Porreca, F., Hruby, V.J., Mitchell, S.A., Palian, M.M. and Polt, R. Natural analgesics from enkephalins with reduced dependence liability. Journal of Medicinal Chemistry, 43: 2586-2590, 2000.
   
• Wells, J.L., Bartlett, J.L., Ananthan, S. and Bilsky, E.J. In vivo pharmacological characterization of SoRI 9409, a nonpeptidic opioid mu agonist/delta antagonist that produces limited antinociceptive tolerance and attenuates morphine physical dependence. Journal of Pharmacology and Experimental Therapeutic, 297: 597-605, 2001.
   
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