MK-801 inhibits the effects of capsaicin in the adult mouse by an action involving phencyclidine (PCP) sites not linked to NMDA activity.
Capsaicin in the adult animal causes antinociception due to the massive release of neurotransmitters, including substance P (SP), from primary afferent C-fibers. The results of the present study indicate that capsaicin-induced antinociception in the adult is sensitive to inhibition by dizocilpine (MK-801). The failure of a high dose (10 nmoles) of (+-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) to mimic the effect of MK-801 (1 nmole) on antinociception induced by 0.8 micrograms of capsaicin suggests that the inhibition by MK-801 is mediated by a phencyclidine (PCP) site but is not associated with NMDA activity. The inability of haloperidol (1 nmole) to affect the actions of capsaicin argues against an interaction with sigma sites. Behavioral sensitization to intrathecally administered kainic acid (KA) has been proposed to reflect similar neuronal activity to that underlying pain transmission. KA sensitization is inhibited by pretreatment with capsaicin (0.8 microgram) or SP(1-7) (10 nmoles) and the influence of MK-801, CPP and haloperidol on these inhibitory effects of capsaicin and SP(1-7) were identical to those on capsaicin-induced antinociception. These data are consistent with the hypothesis that the antinociceptive effect of capsaicin in the adult is similar to that of the N-terminus of SP, both of which involve a pathway sensitive to MK-801 but not mediated by NMDA-type activity.
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Department of Veterinary Pathobiology, University of Minnesota, St. Paul 55108.
Larson
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D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002211:Capsaicin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D007278:Injections, Spinal; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017478:Receptors, Phencyclidine / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology
D010446:Peptide Fragments; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D017478:Receptors, Phencyclidine; D013373:Substance P; D016291:Dizocilpine Maleate; C036877:substance P (1-7); C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D006220:Haloperidol; D002211:Capsaicin; D007608:Kainic Acid