Potent analgesic and anti-inflammatory actions of a novel thymulin-related peptide in the rat
Potent analgesic and anti-inflammatory actions of a novel thymulin-related peptide in the rat
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DOI：
10.1038/sj.bjp.0704793
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发表时间：
2002-07-01
影响因子：
7.3
通讯作者：
Saadé, NE
中科院分区：
文献类型：
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作者：
Safieh-Garabedian, B;Dardenne, M;Saadé, NE
本研究探讨了PAT（胸腺素肽类似物）在两种大鼠炎症性痛觉过敏模型中的作用。2 .用PAT（1、5或25马克杯，100毫升生理盐水，1、1、5或25马克杯）预处理，以剂量依赖的方式，减少了由爪压（PP）试验确定的机械性痛觉过敏和由热板（HP）、爪浸（PI）和甩尾（TF）试验确定的热痛觉过敏与已知能拮抗白细胞介素(IL)-1 β或IL-1 β和PGE(2)机制的三肽K(D)PT和K(D)PV相比，低剂量的PAT具有更强的抗痛觉作用当与甾体（地塞米松）和非甾体（吲哚美辛）抗炎药（NSAID）的效果比较时，PAT表现出相同的镇痛作用经PAT预处理后，il -1 β、IL-6、tnf - α和NGF浓度升高明显降低。注射ET产生以痛觉过敏和发热为特征的疾病行为。7 . PAT预处理可预防痛觉过敏，使体温维持在正常范围内，并伴有肝脏中促炎细胞因子和PGE2水平的下调在使用的所有剂量中，PAT都没有导致大鼠的生理参数或正常行为的任何明显变化PAT的抗痛觉和抗炎作用可归因于，至少部分归因于促炎介质的下调。
I The present study examines the effect of PAT (peptide analogue of thymulin) in two rat models of inflammatory hyperalgesia induced by either i.pl. (1.25 mug in 50 mul saline) or i.p. (50 mug in 100 mul) injections of endotoxin ET.2 Pretreatment with PAT (1, 5 or 25 mug in 100 mul saline, i.p.) decreased, in a dose dependent manner, both mechanical hyperalgesia, determined by the paw pressure (PP) test and thermal hyperalgesia determined by the hot plate (HP), the paw immersion (PI) and the tail flick (TF) tests.3 Compared to the tripeptides K(D)PT and K(D)PV, known to antagonize interleukin (IL)-1beta or IL-1beta and PGE(2) mechanisms, PAT, at lower dosages, exerted stronger anti-hyperalgesic effects.4 When compared with the effect of a steroidal (dexamethasone) and a non-steroidal (indomethacin) anti-inflammatory drugs (NSAID), PAT demonstrated equal analgesic actions.5 Pretreatment with PAT, reduced significantly the increased concentration of IL-1beta, IL-6, TNF-alpha and NGF due to i.pl. injection of ET.6 Injection of i.p. ET produced sickness behaviour characterized by hyperalgesia and fever. Pretreatment with PAT prevented the hyperalgesia and maintained the body temperature within the normal range and was accompanied by a down-regulation of the levels of pro-inflammatory cytokines and PGE2 in the liver.7 PAT, in all doses used, did not result in any evident changes in the physiological parameters or in the normal behaviour of the rats.8 The anti-hyperalgesic and anti-inflammatory effects of PAT can be attributed, at least partially, to the down-regulation of pro-inflammatory mediators.