Transmission of chronic nociception by spinal neurons expressing the substance P receptor.
Substance P receptor (SPR)-expressing spinal neurons were ablated with the selective cytotoxin substance P-saporin. Loss of these neurons resulted in a reduction of thermal hyperalgesia and mechanical allodynia associated with persistent neuropathic and inflammatory pain states. This loss appeared to be permanent. Responses to mildly painful stimuli and morphine analgesia were unaffected by this treatment. These results identify a target for treating persistent pain and suggest that the small population of SPR-expressing neurons in the dorsal horn of the spinal cord plays a pivotal role in the generation and maintenance of chronic neuropathic and inflammatory pain.
Nichols
M L
ML
Department of Preventive Sciences, University of Minnesota, Minneapolis, MN 55455, USA.
Allen
B J
BJ
Rogers
S D
SD
Ghilardi
J R
JR
Honore
P
P
Luger
N M
NM
Finke
M P
MP
Li
J
J
Lappi
D A
DA
Simone
D A
DA
Mantyh
P W
PW
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D000922:Immunotoxins; D007249:Inflammation / Q000503:physiopathology; D008026:Ligation; D009699:N-Glycosyl Hydrolases; D009437:Neuralgia / Q000188:drug therapy / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology*; D010940:Plant Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013127:Spinal Nerves; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D000922:Immunotoxins; D010940:Plant Proteins; D018040:Receptors, Neurokinin-1; D054789:Ribosome Inactivating Proteins, Type 1; D013373:Substance P; D009699:N-Glycosyl Hydrolases; D000076985:Saporins