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INDIVIDUAL RESEARCHER

Lindsay B. Hough , Ph.D.
Professor
e-mail: houghl@mail.amc.edu


Education

1978 - Ph.D. from University of Michigan


Current Research

 
Pain can be a severe, debilitating, chronic condition for which there are no adequate, safe, non-addicting medications. The brain contains neuronal circuitry for processing painful stimuli from the environment, but also posesses intrinsic neuronal networks capable of relieving pain. 
 
Our neuropharmacology lab seeks to understand the chemical basis of neuronal pain relief by studying the mechanism(s) of action of centrally-acting analgesic drugs.  Earlier studies of the pain-relieving properties of histamine-containing neurons led to the discovery of improgan, a powerful new pain-relieving drug that acts independently of known opioid mechanisms. One of the current lab interests is to identify the improgan analgesic receptor. 
 
In searching for the improgan receptor, we recently found a critical role for enzymes of the cytochrome P450 family in the actions of both opioid and non-opioid analgesic drugs.  A second current project is to identify the specific analgesia-relevant enzymes, and to understand the nature of these enzymatic reactions. These studies may help to develop new analgesics based on these reactions. 
 
Our lab is also interested in the pain-relieving properties of drugs acting at the histamine H3 receptor.



References

  1. Conroy, J. L., Fang, C., Gu, J., Zeitlin, S. O., Yang, W., Yang, J., VanAlstine, M. A., Nalwalk, J. W., Albrecht, P.J., Mazurkiewicz, J. E., Snyder-Keller, A., Shan, Z., Zhang, S., Wentland, M.P., Behr, M., M. P., Knapp, B. I., Bidlack, J. M., Zuiderveld, O. P., Leurs, R., Ding, X., and Hough, L. B., Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling, Nature Neurosci. 2010, 13:284-286.


  2. Hough, L.B. and Rice, F., “H3 Receptors and Pain Modulation: Peripheral, Spinal and Brain Interactions”, J. Pharmacol. Exp. Ther. 2011, 336:30-37.


  3. Haas, H.L., Blandina, P., Leurs, R ,and Hough, L.B. “Histamine” in Basic Neurochemistry, 8th Ed., ed. S.T. Brady, R.W. Albers, and D.L. Price, Elsevier Academic Press, Amsterdam, 2012, pp. 323-341.


  4. Hough, L.B., Nalwalk, J.W., Cleary, R.A., Phillips, J.G., Fang, C. Yang, W. and Ding, X., Deficits in neuronal cytochrome P450 activity attenuate opioid analgesia but not opioid side effects, Eur. J. Pharmacol. 2014, 740: 255-262.


  5. Hough, L. B., Nalwalk, J. W., Yang, J., Conroy, J. L., VanAlstine, M.A., Yang, W., Gargano, J., Shan, Z., Zhang, S.-Z., Wentland, M.P., Phillips, J.G., Knapp, B. I., Bidlack, J. M., Zuiderveld, O. P., Leurs, R., and Ding, X., Brain P450 epoxygenase activity is required for the antinociceptive effects of improgan, a non-opioid analgesic, Pain, 2011, 152:878-887.


  6. Hough, L.B., Nalwalk, J.W., Yang, W. and Ding, X., Significance of neuronal cytochrome P450 activity in opioid-mediated stress-induced analgesia, Brain Research, 2014, 1578: 30-37.