Substance P N-terminal metabolites and nitric oxide mediate capsaicin-induced antinociception in the adult mouse.
The present investigation describes the antinociceptive effect of capsaicin in the acetic acid-induced abdominal stretch assay and its mediation by substance P(1-7) fragment [SP(1-7)] and nitric oxide (NO). When injected intrathecally 24 hr before testing, SP(1-7) produced a dose-related decrease in the number of abdominal stretches induced by an i.p. injection of acetic acid. The antinociceptive effect of SP(1-7) (10 nmol) persisted for 62 hr after its injection, a time course that was similar to that produced by a dose of capsaicin (2.6 nmol) that produced an effect of similar magnitude. Antinociception induced by 10 nmol of SP(1-7) was completely reversed by coadministration of 10 nmol of D-SP(1-7); the equivalent antinociception produced by capsaicin was reversed by as small a dose as 1 nmol of D-SP(1-7). The guanylate cyclase inhibitor, methylene blue, at a dose of 10 nmol, prevented both SP(1-7)- and capsaicin-induced antinociception. Capsaicin-induced, but not SP(1-7)-induced, antinociception was prevented by Nw-nitro-L-arginine methyl ester, an NO synthase inhibitor. This inhibition of capsaicin was reversed by coadministration of 120 nmol of L-arginine. Reduced hemoglobin did not prevent capsaicin-induced antinociception. These findings suggest NO is produced and acts within capsaicin-sensitive primary afferent fibers in the dorsal spinal cord to mobilize substance P, resulting in N-terminal induced-antinociception.
Kreeger
J S
JS
Department of Veterinary PathoBiology, University of Minnesota, St. Paul.
Kitto
K F
KF
Larson
A A
AA
D000698:Analgesia; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology*
D010446:Peptide Fragments; D009569:Nitric Oxide; D013373:Substance P; C036877:substance P (1-7); D001120:Arginine; D002211:Capsaicin; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester