The Laboratory of Experimental Neurology at the VAMC is dedicated to studies of the neurobiology of pain perception using highly selective targeted toxins, specifically, substance P-saporin, which specifically destroys lamina I neurons in the dorsal horn of the spinal cord that express the substance P receptor. Intrathecal injection of this toxin uniquely blocks the development of hyperalgesia after repetitive C nociceptor activation. Other toxins include dermorphin-saporin which is targeted at the mu opiate receptor and is being used to analyze the site of action of morphine as well as the endogenous descending analgesic system along with anti-DBH-saporin (noradrenergic toxin). Lesions from these toxins are assessed using immunohistochemistry and image analysis techniques. The lab also is active in developing and characterizing operant behavioral tests of pain perception in rodents. Ultimately, the targeted toxins are being developed for clinical trials in treatment of chronic, intractable pain. Opportunites are available for short or long research experiences in the neurobiology of pain.

Selected Bibliography:

Wiley, R.G. and Lappi, D.A. Destruction of Neurokinin-1 receptor expressing cells in vitro and in vivo using substance P-saporin in rats. Neurosci. Lett. 1997;230:97-100.

Mantyh,P.W., Rogers, S.D., Honore, P., Allen, B.J., Ghilardi, J.R., Li, J., Daughters, R.S., Lappi, D.A., Wiley, R.G., Simone, D.A. Inhibition of Hyperalgesia by Ablation of Lamina I Spinal Neurons Expressing the Substance P Receptor. Science 1997; 278:275-279.

Wiley, R.G. and Lappi, D.A. Targeting neurokinin-1 receptor-expressing neurons with [Sar9,Met(O2)11]substance P-saporin. Neurosci. Lett. 1999;277:1-4.