J. Michael Walker

A.B., Indiana University, 1973
Ph.D., The Ohio State University, 1979
Postdoctoral Fellow, University of Michigan

Research Interests

We investigate the neurochemistry of pain with the aim of 1) identifying neurochemicals that produce and inhibit pain, 2) determining the interactions between these neurochemicals and the circuits within the nervous system that carry pain messages or modulate pain, and 3) finding out how we may manipulate the chemistry within these circuits to shut pain off. During the past decade much of our energy focused on studies of cannabinoids (molecules similar to THC, the active ingredient in marijuana) to determine whether cannabinoids suppress neural circuits that carry pain messages to the brain and whether endocannabinoids (marijuana-like substances produced by the body) serve naturally to modulate pain sensitivity. These studies of endocannabinoids led us to a more recent line of work in which we identified a number of new biomolecules that influence pain sensitivity. One of these, which we named NADA, has the surprising quality of producing pain through the same molecular mechanism as that used by hot chili peppers. In fact, NADA (and its cousin OLDA) have a striking structural similarity to capsaicin, the component of peppers that gives them their "heat." We conjecture that NADA and OLDA serve naturally to produce burning pain sensations when they are produced. The effort to identify these compounds is part of a larger enterprise that has been termed lipidomics, which refers to research that aims to identify all of the important biological lipids. In the coming years, we hope to identify and characterize important new molecules that control pain sensitivity, and to better understand the controls over the synthesis and secretion of pain-related molecules in the brain and other parts of the body. A more complete description of the research in our laboratory can be found on our lab webpage (Walker Lab Website).

Representative Publications

Chu, C.J., Huang, S.M., De Petrocellis, L., Gisogno, T., Ewing, S.A., Miller, J.D., Zipkin, R.E., Daddario, N., Appendino, G., Di Marzo, V., and Walker, J.M. (2003). N- Oleoyldopamine: a novel endogenous capsaicin-like lipid that produces hyperalgesia. Journal of Biological Chemistry, 278: 13633-13639.

Huang, S.M., Bisogno, T., Trevisani, M., Al-Hayani, A., De Petrocellis, L., Fezza, F., Tognetto, M., Petros, T.J., Krey, J.F., Chu, C.J., Miller, J.D., Davies, S.N., Geppetti, P., Walker, J.M., and DiMarzo, V. (2002). An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proceedings of the National Academy of Sciences (USA), 99: 8400-8405.

Walker, J.M. and Huang, S.M. (2002). Endocannabinoids in pain modulation. Prostaglandins, Leukotrienes, and other Fatty Acids, 66: 234-242.

Walker, J.M. and Huang, S.M. (2002). Cannabinoid Analgesia. Pharmacology and Therapeutics, 95: 122-135.

Burstein, S.H., Huang, S.M., Petros, T.J., Rossetti, R.G., Walker, J.M., and Zurier, R.B. (2002). regulation of anandamide tissue levels by N-arachidonylglycine. Biochemical Pharmacology, 64: 1147-1150.

Walker, J.M., Krey, J.F., Chu, C.J., and Huang, S.M. (2002). Endocannabinoids and related fatty acid derivatives in pain modulation. Chemistry and Physics of Lipids, 121: 59-72.

Walker, J.M., Strangman, N.M., and Huang, S.M. (2001). Cannabinoids and pain. Pain Research and Management, 6: 74-79.

Huang, S.M., Bisogno, T., Petros, T.J., Chang, S.Y., Zavitsanos, P.A., Zipkin, R.E., Sivakumar, R., Coop, A., Maeda, D.Y., De Petrocellis, L., Burstein, S., Di Marzo, V., and Walker, J.M. (2001). Identification of a new class of molecules, the arachidonyl amino acids, and characterization of one member that inhibits pain . Journal of Biological Chemistry, 276: 42639-42644.

Walker, J.M., Huang, S.M., Strangman, N.M., and Sañudo-Peña, M.C. (2000). Identification of the role of endogenous cannabinoids in pain modulation: strategies and pitfalls. Journal of Pain, 1: 20-32.

Sañudo-Peña, M.C., Tsou, K., Romero, J., Mackie, K., and Walker, J.M. (2000). Role of the superior collicullus in the motor effects of cannabinoids and dopamine. Brain Research, 853:207-214.