Todd W. Vanderah,
Assistant Professor of Anesthesiology and Pharmacology, Ph.D., University of Arizona, 1995
vanderah@u.arizona.edu

Mechanisms and pharmacology of acute and chronic models of pain; endogenous opioid systems; sensory neural systems; opioid tolerance; antinociceptive synergy between cannabinoids and opioids.

Research Activities

Opioids, such as morphine and codeine, are currently the medicine of choice for pain relief. Yet, the presence of increased pain requires increasing doses of an opioid to elicit the same degree of pain relief - more pain means a need for more opioid.  The increased need for opioid to attain the same level of pain relief has been termed “opioid tolerance”.  In addition, clinical reports have described patients being treated with higher and higher doses of opioids for an extended period of time result in the development of unexpected, paradoxical pain (pain in regions unrelated to the original site of injury) due to the opioid itself. Our current research goal is to understand the neural-mediated mechanism underlying opioid tolerance and opioid-induced pain.

Our laboratory is measuring the release of neurotransmitters at the level of the spinal cord in animals treated with opioids. Data suggest that the activation of specific neurons at the level of the brainstem result in the manifestation of increased pain in the presence of opioids.  For these reasons, it appears that opioid antinociceptive tolerance may, in fact, be the result of increased levels of pain elicited by activation of supraspinal pain facilitation mechanisms and enhanced pain neurotransmitter release at the level of the spinal cord.  Furthermore, using microdialysis, we are measuring neurotransmitter release both at the level of the spinal cord and brain in regions responsible for modulating sensory input. Studies are currently being performed to look at how both pharmacological compounds as well as antisense oligodeoxynucleotide to endogenous proteins alter the behavioral and neurotransmitter response.  The ultimate goals of this research are to identify novel pharmacotherapies for the treatment of pain, further understand the physiological basis of pain, and discover how the nervous system adapts to persistent sensory input from specific types of nerve fibers.

Publications (Query PubMed for this investigator)

Wang, Z., Gardell, L.R., Ossipov, M.H., Vanderah, T.W., Brennan, M.B., Hochgeschwneder, U., Hruby V.J., Malan Jr., T.P., Lai, J. and Porreca, F.:  Pronociceptive actions of dynorphin maintain chronic neuropathic pain. J. Neurosci., in press, 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. J. Neurosci., 21:(1)279-286, 2001.

Hosohata, Y, Vanderah, T.W., Burkey, T.H., Ossipov, M.H., Kovelowski, C.J., Ichiro, S., Uhl, G.R., Zhang, X., Rice, K.C., Roeske, W.R., Hruby, V.J., Yamamura, H.I., Lai, J., and Porreca, F.: Delta-Opioid receptor agonists produce antinociception and [35S]GTPgammaS binding in µ receptor knockout mice. European Jouranl of Pharmacology, 388:241-248, 2000.

Hosohata, K., Logan, J.K., Varga, E., Burkey, T.H., Vanderah, T.W., Porreca, P., Hruby, V.J., Roeske, W.R. and Yamamura, H.I.: The role of G protein Gamma2 subunit in opioid antinociception in mice. European Jouranl of Pharmacology, 392:R9-R11, 2000.

Vanderah, T.W., Gardell, L.R., Burgess, S.E., Ibrahim, M., Zhong, C-M., Ossipov, M.H., Lai, J., Malan, Jr. T.P. and Porreca, F.: Repeated Spinal Opioid Administration Produces Abnormal Pain and Antinociceptive Tolerance which is Reversed by Dynorphin Antiserum. J Neurosci., 20:(18) 7074-7079, 2000.

Porreca, F., Vanderah, T.W., Zhong, C.-M., Burgess, S.E.,  Gardell, L.R., Malan Jr., T.P.,  Ossipov, M.H.,  Rogers, S., Lappi, D.A., Lai, J. and Mantyh, P.W.: Mediation of Neuropathic Pain by Tonic Activity of Descending Facilitation in the Rostral Ventromedial Medulla, submitted, Nature, 2000.

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. J. Neurosci., in Press, 2000.

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