ACETAMINOPHEN BLOCKS SPINAL HYPERALGESIA INDUCED BY NMDA AND SUBSTANCE-P

Citation
R. Bjorkman et al., ACETAMINOPHEN BLOCKS SPINAL HYPERALGESIA INDUCED BY NMDA AND SUBSTANCE-P, Pain, 57(3), 1994, pp. 259-264
Citations number
25
Categorie Soggetti
Neurosciences
Journal title
PainACNP
ISSN journal
03043959
Volume
57
Issue
3
Year of publication
1994
Pages
259 - 264
Database
ISI
SICI code
0304-3959(1994)57:3<259:ABSHIB>2.0.ZU;2-P
Abstract
The hypothesis tested was that inhibition of the L-arginine-nitric oxi de (NO) pathway may represent a potential central mechanism of action for acetaminophen (paracetamol). Spinal administration of N-methyl-D-a spartate (NMDA, 0.5 nmol), pha-amino-3-hydroxy-5-methyl-4-isoxazolepro pionate (AMPA, 0:1 nmol) or substance P (SP, 0.5 nmol) to the rat prov oked a specific behaviour characterized by biting, scratching and lick ing (BSL). This behaviour was antagonized by pretreatment with acetami nophen 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 acetaminoph en is related to inhibition of NO generation. Potential mechanisms for this may involve NMDA and SP. Our data suggest that a significant por tion of the analgesic effect of acetaminophen, when used clinically, m ay be related to an interaction with the central nervous system L-argi nine-NO pathway.