对乙酰氨基酚可阻断由N-甲基-D-天冬氨酸和P物质诱导的脊髓痛觉过敏。

Acetaminophen blocks spinal hyperalgesia induced by NMDA and substance P.

作者信息

Björkman R, Hallman K M, Hedner J, Hedner T, Henning M

机构信息

Department of Pharmacology, University of Gothenburg and Sahlgren's Hospital, GothenburgSweden Department of Clinical Pharmacology, University of Gothenburg and Sahlgren's Hospital, GothenburgSweden.

出版信息

Pain. 1994 Jun;57(3):259-264. doi: 10.1016/0304-3959(94)90001-9.

DOI:10.1016/0304-3959(94)90001-9

PMID:7524008

Abstract

The hypothesis tested was that inhibition of the L-arginine-nitric oxide (NO) pathway may represent a potential central mechanism of action for acetaminophen (paracetamol). Spinal administration of N-methyl-D-aspartate (NMDA, 0.5 nmol), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, 0.1 nmol) or substance P (SP, 0.5 nmol) to the rat provoked a specific behaviour characterized by biting, scratching and licking (BSL). 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.

摘要

所检验的假设是，抑制L-精氨酸-一氧化氮（NO）途径可能是对乙酰氨基酚（扑热息痛）潜在的中枢作用机制。向大鼠脊髓注射N-甲基-D-天冬氨酸（NMDA，0.5纳摩尔）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA，0.1纳摩尔）或P物质（SP，0.5纳摩尔）会引发一种以咬、抓和舔（BSL）为特征的特定行为。对NMDA和SP而言，这种行为会被对乙酰氨基酚预处理所拮抗，但对AMPA则不然。此外，一氧化氮合酶（NOS）的天然底物L-精氨酸给药可轻易逆转对乙酰氨基酚的镇痛作用，而D-精氨酸则不能。这表明对乙酰氨基酚的镇痛作用与抑制NO生成有关。其潜在机制可能涉及NMDA和SP。我们的数据表明，临床上使用对乙酰氨基酚时，其镇痛作用的很大一部分可能与它和中枢神经系统L-精氨酸-NO途径的相互作用有关。