Long-lasting hyperalgesia induced by fentanyl in rats -: Preventive effect of ketamine
Long-lasting hyperalgesia induced by fentanyl in rats -: Preventive effect of ketamine
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DOI：
10.1097/00000542-200002000-00029
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发表时间：
2000-02-01
期刊：
影响因子：
8.8
通讯作者：
Simonnet, G
中科院分区：
文献类型：
--
作者：
Célèrier, E;Rivat, C;Simonnet, G
背景资料：据报道，μ-阿片受体激活导致N-甲基-D-天冬氨酸（NMDA）受体水平上谷氨酸突触有效性的持续增加，这是一种与对疼痛的中枢超敏反应相关的系统。一种假设是，术后疼痛可能部分来自阿片类药物治疗本身引起的NMDA疼痛易化过程的激活。作者在这里测试的有效性阿片类镇痛芬太尼引起延迟增强疼痛sensitivity.Methods：的后果四团注射（每15分钟）芬太尼（20-100 μ g/kg每次注射，皮下）立即（数小时）和长期（数天）的敏感性伤害性刺激大鼠（爪压发声试验）进行了评价。NMDA受体拮抗剂氯胺酮联合应用的效果结果：芬太尼给药表现出双相的时间依赖性效应：第一，及早作出反应（2-5小时）与伤害性阈值的显著增加相关（镇痛），第二，与伤害性阈值持续降低相关的后期反应（最长效果为5天）低于基础值（最大效果降低30%），表明痛觉过敏。芬太尼剂量越高，芬太尼诱导的痛觉过敏越明显。氯胺酮预处理，这对自己没有镇痛作用，增强了早期的反应（镇痛），并防止发展的长期持久的hyperalgesia.Conclusions：芬太尼激活NMDA疼痛易化过程，反对镇痛，并导致持久的增强疼痛敏感性。
Background: It has been reported that mu-opioid receptor activation leads to a sustained increase in glutamate synaptic effectiveness at the N-methyl-D-aspartate (NMDA) receptor level, a system associated with central hypersensitivity to pain. One hypothesis is that postoperative pain may result partly from the activation of NMDA pain facilitatory processes induced by opiate treatment per se. The authors tested here the effectiveness of the opiate analgesic fentanyl for eliciting a delayed enhancement in pain sensitivity.Methods: The consequences of four bolus injections (every 15 min) of fentanyl (20-100 mu g/kg per injection, subcutaneously) on immediate (for several hours) and long-term (for several days) sensitivity to nociceptive stimuli in the rat (paw-pressure vocalization test) were evaluated. The effects of the combination of the NMDA-receptor antagonist ketamine (10 mg/kg, subcutaneously) with fentanyl also were assessed.Results: Fentanyl administration exhibited a biphasic time-dependent effect: first, an early response (for 2-5 h) associated with a marked increase in nociceptive threshold (analgesia), and second, a later response associated with sustained lowering of the nociceptive threshold (5 days for the longest effect) below the basal value (30% of decrease for the maximal effect) indicative of hyperalgesia. The higher the fentanyl dose used, the more pronounced was the fentanyl-induced hyperalgesia. Ketamine pretreatment, which had no analgesic effect on its own, enhanced the earlier response (analgesia) and prevented the development of long-lasting hyperalgesia.Conclusions: Fentanyl activates NMDA pain facilitatory processes, which oppose analgesia and lead to long-lasting enhancement in pain sensitivity.