Frank Porreca,
Professor of Pharmacology, Ph.D., Temple University, 1982.
frankp@u.arizona.edu

Neurobiology of pain.

Research Activities

The research explores the neural basis of normal and pathological pain states. Our emphasis is on understanding chronic neuropathic pain, the type of pain often associated with injuries to peripheral nerves. This type of pain affects some 50 million people in the US alone. Such pain is debilitating and less than 50% of all patients report any significant benefit from currently available medical therapies. The pain is abnormal because it is produced by innappropriate, low-intensity stimuli which are normally innocuous making normal activies (e.g., clothing, bathing etc) difficult or impossible. The physiological basis of such abnormal pain and how the nervous system is altered so that innocuous sensory signals are now interpreted as pain is investigated using behavioral, biochemical and immunohistochemical approaches.

A key characteristic of the post-nerve-injury state is the tremendous plasticity that is seen in both the peripheral and the central nervous system. It is hypothesized that such neural plasticity is responsible for generating the abnormal pain. Changes in the expression of endogenous neurotransmitters in the spinal cord are studied as a possible basis by which alteration of sensory processing occurs. Changes in expression of sodium channels at peripheral nerve terminals are also hypothesized to be the basis of such abnormal pain. Finally, changes in expression of substances in the brainstem and sustained discharge of cells in the brainstem to activate descending pain modulatory (facilitatory) systems are also explored as a basis of the chronic pain state. The ultimate goals of this research are to identify novel pharmacotherapies for treatment of abnormal pain, and further, to simply understand the plasticity of the nervous system where the nerve-injury is simply a perturbation of the normal functioning of the nervous system. Along this line, a new area of interest is the role of trophic factors in maintenance of the phenotype of cells in the dorsal root ganglia and in the spinal dorsal horn. Our research is currently focusing on the role of NGF and GDNF in the expression of specific immunohistochemical markers in these areas and the changes that occur after injury.

Publications (Query PubMed for this investigator)

Sun, H., Ren, K., Zhong, C.M., Ossipov, M.H., Malan, Jr., T.P., Lai, J. and Porreca, F.: Tactile Allodynia after Peripheral Nerve Injury is Mediated Through Ascending Spinal Dorsal Column Projections. In press, Pain, 2001.

Wang, Z., Gardell, L.R., Ossipov, M.H., Vanderah, T.W., Brennan, M.B., Hochgeschwender, U., Hruby, V.J., Malan, Jr., T.P., Lai, J. and Porreca, F.: Pronociceptive Actions of Dynorphin Maintain Chronic Neuropathic Pain. In Press, Journal of Neuroscience, 2001.

Vanderah, T.W., Suenaga, N.M.H., Ossipov, M.H., Malan, Jr., T.P., Lai, J. and Porreca, F.: Tonic Descending Facilitation from the Rostral Ventromedial Medulla Mediates Opioid-Induced Abnormal Pain and Antinociceptive Tolerance. Journal of Neuroscience 21:279-286, 2001.

Kovelowski, C.J., Ossipov, M.H., Sun, H., Lai, J., Malan, Jr., T.P. and Porreca, F.:  Supraspinal cholecystokinin may drive tonic descending facilitation mechanisms to maintain neuropathic pain in the rat. Pain 87:265-273, 2000.

Malan, Jr., T.P., Ossipov, M.H., Gardell, L.R., Ibrahim, M., Bian, D., Lai, J. and Porreca, F.:  Extraterritorial Neuropathic Pain Correlates with Multisegmental Elevation of Spinal Dynorphin in Nerve-Injured Rats. Pain 86: 185-194, 2000.

Vanderah, T.W., Gardell, L.R., Burgess, S.E., Ibrahim, M., Dogrul, A., Zhong, C.-M., Zhang, E.-T., Malan, Jr., T.P., Ossipov, M.H., Lai, J. and Porreca, F. Dynorphin Promotes Abnormal Pain and Spinal Opioid Antinociceptive Tolerance. Journal of Neuroscience, 20:7074-7079, 2000.

Porreca, F., Lai., J., Bian, D., Wegert, S., Ossipov, M.H., Eglen, R.M., Kassotakis, L., Novakovic, S., Sangameswaran, L. and Hunter, J.C. Blockade of neuropathic pain by antisense targeting of PN3/SNS, a TTX-resistant sodium channel, in sensory neurons. Proceedings of the National Academy of Science (USA) 96:7640-7644, 1999.

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