Involvement of dynorphin A and not substance P in the spinal antianalgesic action of capsaicin against morphine-induced antinociception in mice.
In previous publications we proposed that dynorphin A (1-17) (Dyn) functions as an antianalgesic agent in the spinal cord of mice. Whether endogenously released or administered directly to the spinal cord, this antianalgesic action attenuates the antinociceptive effect of morphine (Mor) in the mouse tail-flick test. Because this action of Dyn in the spinal cord appeared to be congruous with the function of substance P (SP), experiments were designed to compare the actions of the two on Mor-induced antinociception. Inhibition of the tail-flick response induced by i.c.v. administration of Mor was attenuated by intrathecal (i.t.) administration of SP or Dyn. This antianalgesic effect of Dyn (5 fmol) but not SP (74 pmol) was antagonized by naloxone and nor-binaltorphimine administered i.t. Capsaicin (Cap) i.t. at a 0.1-microgram dose, like SP and Dyn, antagonized the antinociceptive effect of Mor given i.c.v. Excellent evidence exists to indicate that, in rats, Cap (30-70 micrograms i.t.) releases SP in the spinal cord and that Mor inhibits this release. Present experiments indicated, however, that i.t. administration of low doses of Cap (0.05-0.5 microgram) in mice preferentially released Dyn and not SP as based on the following results. 1) The antianalgesic action of Cap i.t. against Mor i.c.v. was antagonized by naloxone and nor-binaltorphimine i.t. as was Dyn i.t. (but not SP i.t.). 2) A SP antagonist, (D-Pro2, D-Phe7, D-Trp9)-SP, did not reverse the effect of Cap or Dyn given i.t., even though it antagonized the effect of SP.(ABSTRACT TRUNCATED AT 250 WORDS)
Arts
K S
KS
Research Service, C. J. Zablocki Veterans Administration Medical Center, Milwaukee, Wisconsin.
Fujimoto
J M
JM
Tseng
L F
LF
D000698:Analgesia; D000818:Animals; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000037:antagonists & inhibitors*; D013131:Spine / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*
D013373:Substance P; D004399:Dynorphins; D009020:Morphine; D002211:Capsaicin