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

• Published in: Science (American Association for the Advancement of Science) Vol. 278; no. 5336; pp. 275 - 279
• Main Authors: Mantyh, Patrick W., Rogers, Scott D., Honore, Prisca, Allen, Brian J., Ghilardi, Joseph R., Li, Jun, Daughters, Randy S., Lappi, Douglas A., Wiley, Ronald G., Simone, Donald A.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 10-10-1997; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Antibodies; Biological and medical sciences; Body Weight; Capsaicin; Cell Membrane - metabolism; Cells, Cultured; Cytotoxicity; Fluorescent Antibody Technique; Fluorescent antibody techniques; Hyperalgesia; Hyperalgesia - physiopathology; Hyperalgesia - therapy; Immunotoxins; Injections, Spinal; Internalization; Medical sciences; N-Glycosyl Hydrolases; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neurons; Neurons - cytology; Neurons - metabolism; Neuroscience; Pain; Pain - physiopathology; Pain Management; Pain Measurement; Plant Proteins - metabolism; Plant Proteins - pharmacology; Proteins; Rats; Rats, Sprague-Dawley; Receptors; Receptors, Neurokinin-1 - biosynthesis; Receptors, Neurokinin-1 - metabolism; Ribonucleic acid; Ribosome Inactivating Proteins, Type 1; RNA; Saporins; Signal Transduction; Spinal cord; Spinal Cord - cytology; Spinal Cord - metabolism; Stimuli; Substance P - metabolism; Substance P - pharmacology; Toxicity; Noxious stimulus; Nervous system diseases; Spinal cord; Substance P; Central nervous system; Peptidergic receptor; Gene expression; Neuropeptide; Tachykinin; Hyperalgesia
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.278.5336.275

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, laminal 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.