Miranda H F, Lemus I, Pinardi G
Faculty of Medicine, University of Chile, Pharmacology Program, 7 Santiago, Chile.
Brain Res Bull. 2003 Aug 30;61(4):417-25. doi: 10.1016/s0361-9230(03)00144-8.
The antinociceptive activity of nonsteroidal anti-inflammatory drugs (NSAIDs) has been explained mainly on the basis of their inhibition of the enzyme cyclooxygenase (COX); however, this inhibition is not enough to completely explain the analgesic efficacy of these drugs. The modulation exerted by serotonergic systems on antinociception is well known. The purpose of the present work was to further explore the role of serotonin in the antinociceptive activity of NSAIDs using the writhing test and the tail-flick test of the mice after the inhibition of serotonin biosynthesis with intraperitoneal p-chlorophenylalanine (p-CPA). Pretreatment with p-CPA produced a significant decrease in the antinociceptive activity of NSAIDs administered either by the intraperitoneal or intrathecal routes, in both algesiometric tests. These results suggest a complementary mechanism of antinociception for NSAIDs, independent of their ability to inhibit the activity of COX, involving the activation of descending serotonergic pathways. By the pharmacological nature of the study, one limitation was the absence of biochemical measurement of the synthesis of 5-HT, since the reduction of the brain 5-HT synthesis by pretreatment with p-CPA will be expressed as a diminished antinociceptive activity of NSAIDs, which would be a new argument to consider NSAIDs acting as central analgesic agents.
非甾体抗炎药（NSAIDs）的抗伤害感受活性主要基于其对环氧化酶（COX）的抑制作用来解释；然而，这种抑制作用不足以完全解释这些药物的镇痛效果。血清素能系统对伤害感受的调节作用是众所周知的。本研究的目的是在腹腔注射对氯苯丙氨酸（p-CPA）抑制血清素生物合成后，利用小鼠扭体试验和甩尾试验进一步探讨血清素在NSAIDs抗伤害感受活性中的作用。在两种痛觉测量试验中，p-CPA预处理均显著降低了腹腔注射或鞘内注射NSAIDs后的抗伤害感受活性。这些结果表明，NSAIDs存在一种独立于其抑制COX活性能力的抗伤害感受补充机制，涉及下行血清素能通路的激活。由于本研究的药理学性质，一个局限性是缺乏5-羟色胺合成的生化测量，因为p-CPA预处理导致的脑5-羟色胺合成减少将表现为NSAIDs抗伤害感受活性降低，这将是认为NSAIDs作为中枢镇痛药起作用的一个新论据。
