Characterization of the hyperalgesic effect induced by intrathecal injection of substance P.
Substance P (SP) was administered to awake rats by injection into the lumbar subarachnoid space via an indwelling cannula. Intrathecal (i.t.) injection of substance P produced a dose-related hyperalgesic response in the tail-pressure assay. This hyperalgesic effect peaked at 1 min and returned to control level within 15 min. Tachyphylaxis to the action of substance P was not observed by successive intrathecal injections. The hyperalgesic effect induced by substance P was increased by pretreatment with naloxone and blocked by a large dose of morphine. A synthetic analogue (D-Pro2, D-Trp7,9)-substance P, was not found to block the action of substance P on mechanical responses. These results suggest that substance P apparently produces a direct action on spinal substance P receptors and the antagonistic effect of morphine on the hyperalgesia induced by substance P may be mediated through a postsynaptic mechanism in the spinal cord.
Matsumura
H
H
Sakurada
T
T
Hara
A
A
Sakurada
S
S
Kisara
K
K
D000818:Animals; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology
D013373:Substance P; D009270:Naloxone; D009020:Morphine; C032132:substance P, prolyl(2)-tryptophan(7,9)-