William D. Willis Jr. Home Page

William D. Willis, Jr., M.D., Ph.D.

A major focus of research in our program at the University of Texas Medical Branch is the study of pain mechanisms. A group of 7 faculty investigators are doing collaborative research using several different experimental models and a number of different approaches, including immunocytochemistry, electron microscopy, electro physiology, neuropharmacology, neurochemical measurements, as well as behavioral analysis, to help solve the difficult problems encountered in the field.

Credentials

Research program

The particular types of pain under investigation include inflammatory pain (arthritis), visceral pain, neuropathic pain and central pain. We also interact with clinicians in the UTMB pain clinic to increase our knowledge of human pain states and current therapeutic methods to treat acute and chronic pain. The two general lines of investigation in my laboratory are the analysis of ascending nociceptive pathways originating in the spinal cord and of descending control systems that allow the brain to modify activity in the ascending nociceptive pathways.

In many studies we record from identified spinothalamic tract cells in anesthetized monkeys as seen in the following figure. The techniques used include extracellular and sometimes intracellular recordings of responses to peripheral stimulation and of alterations produced by electrical stimuli applied at sites in the brain known to modulate behavioral responses to painful stimuli. In many experiments, the release of neurotransmitters is determined using microdialysis, and the effects of drugs are examined using iontophoresis or administration of the drugs by microdialysis.

Changes in the responses of an STT cell to mechanical stimuli applied away from the site of an intradermal injection of capsaicin. (A) Background activity of the cell prior to injection of capsaicin. (B) Capsaicin was injected at the time indicated by the arrow. Note the change in time scale. The injection site is indicated by the arrow on the drawing at the bottom. (C) Responses to brushing the skin at sites 1-5 (shown on the drawing). (D) Increased responses after capsaicin injection. Similarly, (E) and (F) show the responses to pressure (PRESS) and (G) and (H) to pinch before and after injection of capaicin. The receptive field increased in size following capsaicin injection (compare doubly and singly hatched areas on the drawing).

Recent Publications

Dougherty, P.M., Palecek, J., Paleckova, V., Sorkin, L.S. and Willis, W.D. The role of NMDA and non-NMDA excitatory amino acid receptors in the excitation of primate spinothalamic tract neurons by mechanical, chemical, thermal and electrical stimuli. J. Neurosci. 12:3025-3041, 1992.

Palecek, J., Dougherty, P.M., Kim, S.H., Paleckova, V., Lekan, H., Chung, J.M., Carlton, S.M. and Willis, W.D. Responses of spinothalamic tract neurons to mechanical and thermal stimuli in an experimental model of peripheral neuropathy in primates. J. Neurophysiol. 68:1951-1966, 1992.

Dougherty, P.M., Palecek, J., Zorn, S. and Willis, W.D. Combined application of excitatory amino acids and substance P produces long-lasting changes in responses of primate spinothalamic tract neurons. Brain Res. Rev. 18:227-246, 1993.

Lin, Q., Peng, Y. and Willis, W.D. Glycine and GABAA antagonists reduce the inhibition of primate spinothalamic tract neurons produced by stimulation in periaqueductal gray. Brain Res. 654:286-302, 1994.

Dougherty, P.M., Palecek, J., Paleckova, V. and Willis, W.D. Neurokinin 1 and 2 antagonists attenuate the responses and NK1 antagonists prevent the sensitization of primate spinothalamic tract neurons after intradermal capsaicin. J. Neurophysiol. 72:1464-1475, 1994.

Rees, H., Sluka, K.A., Westlund, K.N. and Willis, W.D. The role of glutamate and GABA receptors in the generation of dorsal root reflexes by acute arthritis in the anaesthetized rat. J. Physiol. 484:437-445, 1995.

and Internet guidelines.

Last updated: 05/20/03