The Medical Student Research Program

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Todd W. Vanderah, Ph.D.
Associate Professor, Pharmacology and Anesthesiology

Department of Pharmacology
Life Sciences North 0560
P.O. Box 245050
Tucson AZ 85724-5050
Phone: 626-7801; Fax: 626-2204
E-mail: vanderah@email.arizona.edu

EDUCATION:

-University of Arizona, 1995 (Ph.D.)

HONORS AND AWARDS:

Dean's List for Excellence in Teaching, 2008

MAJOR AREAS OF RESEARCH INTEREST:

- mechanisms and pharmacology of acute and chronic models of pain
- neuronal integration in pain pathways
- neurochemical release during conditions of neuropathy
- neuronal plasticity
- antinociceptive synergy between cannabinoids and opioids
- endogenous opioid systems
- sensory neural systems
- opioid tolerance
- activation of cannabionoid receptors
- opioid receptor pharmacology
- novel targets for drug discovery

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.

Selected Publications:

King T, Ossipov MH, Vanderah TW, Porreca F, Lai J: Is paradoxical pain induced by sustained opioid exposure an underlying mechanism of opioid antinociceptive tolerance?. NeuroSignals. 14(4):194-205, 2005.

King T, Gardell LR, Wang R, Vardanyan A, Ossipov MHM Malan TP Jr., Vanderah TW, Hunt SP, Hruby VJ, Lai J, Porreca F: Role of NK-1 neurotransmission in opioid-induced hyperalgesia. Pain. 116(3):276-88, 2005.

Ossipov MH, Lai J, King T, Vanderah TW, Porreca F: Underlying mechanisms of pronociceptive consequences of prolonged morphine exposure. Biopolymers. 80(2-3):319-24, 2005.

Gavva NR, Tamir R, Qu Y, Klionsky L, Zhang TJ, Immke D, Wang J, Zhu D, Vanderah TW, Porreca F, Doherty EM, Norman MH, Wild KD, Bannon AW, Louis JC, Treanor JJ: AMG 9810 [(E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)acrylamide], a novel vanilloid receptor 1 (TRPV1) antagonist with antihyperalgesic properties. Journal of Pharmacology & Experimental Therapeutics. 313(1):474-84, 2005.

Varga EV, Hosohata K, Borys D, Navratilova E, Nylen A, Vanderah TW, Porreca F, Roeske WR, Yamamura HI: Antinociception depends on the presence of G protein gamma2-subunits in brain. European Journal of Pharmacology. 508(1-3):93-8, 2005.