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Science 10 October 1997:
Vol. 278. no. 5336, pp. 275 - 279
DOI: 10.1126/science.278.5336.275
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Reports

Inhibition of Hyperalgesia by Ablation of Lamina I Spinal Neurons Expressing the Substance P Receptor

Patrick W. Mantyh, * Scott D. Rogers, Prisca Honore, Brian J. Allen, Joseph R. Ghilardi, Jun Li, Randy S. Daughters, Douglas A. Lappi, Ronald G. Wiley, Donald A. Simone

Substance P is released in the spinal cord in response to painful stimuli, but its role in nociceptive signaling remains unclear. When a conjugate of substance P and the ribosome-inactivating protein saporin was infused into the spinal cord, it was internalized and cytotoxic to lamina I spinal cord neurons that express the substance P receptor. This treatment left responses to mild noxious stimuli unchanged, but markedly attenuated responses to highly noxious stimuli and mechanical and thermal hyperalgesia. Thus, lamina I spinal cord neurons that express the substance P receptor play a pivotal role in the transmission of highly noxious stimuli and the maintenance of hyperalgesia.

P. W. Mantyh, S. D. Rogers, P. Honore, B. J. Allen, J. R. Ghilardi, Molecular Neurobiology Laboratory (151), Veterans Administration Medical Center, Minneapolis, MN 55417; and Department of Preventive Sciences, School of Dentistry, University of Minnesota and the Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455, USA.
J. Li, R. S. Daughters, D. A. Simone, Department of Preventive Sciences, School of Dentistry, University of Minnesota and the Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455, USA.
D. A. Lappi, Advanced Targeting Systems, 1600 Faraday Avenue, Carlsbad, CA 92008, USA.
R. G. Wiley, Neurology Service (147), Veterans Administration Medical Center, Nashville, TN 37212, USA.
*   To whom correspondence should be addressed. E-mail: manty001{at}maroon.tc.umn.edu

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