Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor.
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.
Mantyh
P W
PW
Molecular Neurobiology Laboratory (151), Veterans Administration Medical Center, Minneapolis, MN 55417, USA. manty001@maroon.tc.umn.edu
Rogers
S D
SD
Honore
P
P
Allen
B J
BJ
Ghilardi
J R
JR
Li
J
J
Daughters
R S
RS
Lappi
D A
DA
Wiley
R G
RG
Simone
D A
DA
D000818:Animals; D002211:Capsaicin; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D006930:Hyperalgesia / Q000503:physiopathology / Q000628:therapy*; D000922:Immunotoxins; D007278:Injections, Spinal; D009699:N-Glycosyl Hydrolases; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010146:Pain / Q000503:physiopathology; D059408:Pain Management; D010147:Pain Measurement; D010940:Plant Proteins / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000096:biosynthesis / Q000378:metabolism*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism; D013373:Substance P / Q000378:metabolism* / Q000494:pharmacology
D000922:Immunotoxins; D010940:Plant Proteins; D018040:Receptors, Neurokinin-1; D054789:Ribosome Inactivating Proteins, Type 1; D013373:Substance P; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D002211:Capsaicin