Acetaminophen blocks spinal hyperalgesia induced by NMDA and substance P

Abstract

Nmol) or substance P (SP, 0.5 nmol) to the rat provoked a specific behaviour characterized by biting, scratching and licking (BSD. This behaviour was antagonized by pretreatment with acetaminophen for NMDA and SP but not for AMPA. Further, the antinociceptive effect of acetaminophen was readily reversed by administration of the natural substrate for nitric oxide synthase (NOS), l-arginine, but not by d-arginine. This suggests that the analgesic effect of acetaminophen is related to inhibition of NO generation. Potential mechanisms for this may involve NMDA and SP. Our data suggest that a significant portion of the analgesic effect of acetaminophen, when used clinically, may be related to an interaction with the central nervous system l-arginine-NO pathway. Abbreviations: N-methyl-d-aspartate; Nitric oxide; Acetaminophen; Nociception; Hyperalgesia; (Rat); ∗Corresponding author: Roland Björkman, Department of Pharmacology, Medicinargatan 7, University of Gothenburg, S-413 90 Gothenburg, Sweden. Tel.: 031-89-26-71 or 031-85-34-21; FAX: 031-45-28-47 or 031-82-17-95. Submitted May 20, 1993; revised October 28, 1993; accepted November 12, 1993. © Lippincott-Raven Publishers....