Role of opioid receptors in the reduction of formalin-induced secondary allodynia and hyperalgesia in rats
Role of opioid receptors in the reduction of formalin-induced secondary allodynia and hyperalgesia in rats
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DOI：
10.1016/j.ejphar.2009.08.001
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发表时间：
2009-10-01
影响因子：
5
通讯作者：
Granados-Soto, Vinicio
中科院分区：
文献类型：
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作者：
Ambriz-Tututi, Monica;Rocha-Gonzalez, Hector I.;Granados-Soto, Vinicio
这项研究评估了外周或鞘内使用Mu、Delta、kappa和伤害素/孤儿FQ(NOP)阿片受体激动剂(吗啡)治疗前后的效果。U-50488[trans-(+/-)-3，4-dichloro-Nmethyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide盐酸盐、D-丙氨酸-亮氨酸-脑啡肽[D-丙氨酸-亮氨酸-5-脑啡肽]和伤害素)对甲状旁腺素诱导的大鼠继发性机械痛和痛觉过敏的影响。1%福尔马林注射后出现急性伤害性行为(缩腿和舔/抬)，继发长期触觉继发性超敏和痛觉过敏。外周(注入福尔马林)或鞘内吗啡治疗后均不能逆转福尔马林引起的继发性超敏和痛觉过敏。相比之下，吗啡的预处理可以阻止这些疼痛行为的发展。鞘内和外周用U-50488或DADLE治疗后，但不是用药前，可显著减少继发性超敏和痛觉过敏。有趣的是，无论给药地点或治疗时间如何，伤害素都能减少这两种疼痛行为。吗啡、去甲肾上腺素、U-50488或伤害素的局部抗伤害性反应分别被纳曲酮、纳曲多、5-胍基吲哚和伤害素(1-13)NH_2阻断。这些结果表明，福尔马林诱导的长期伤害性行为受选择性阿片受体激动剂的不同调节。此外，数据表明，当伤害性行为建立时，外周和脊髓的三角洲和kappa阿片受体是重要的。相比之下，在感觉系统没有改变的情况下，在损伤开始时，u阿片受体更重要。NOP受体参与抑制伤害性行为的发展和维持。结果表明，福尔马林注射引起的大量传入输入启动了外周和脊髓加工的长期差异改变，从而影响阿片受体激动剂的疗效。(C)2009爱思唯尔B.V.保留所有权利。
This study assesses the effects of peripheral or intrathecal pre-treatment or post-treatment with mu, delta, kappa and nociceptin/orphanin FQ (NOP) opioid receptor agonists (morphine. U-50488 [trans-(+/-)-3,4-dichloro-Nmethyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide hydrochloride], DADLE [D-Ala2-Leu5-enkephalin] and nociceptin, respectively) on formal in-induced secondary mechanical allodynia and hyperalgesia in rats. 1% Formalin injection produced acute nociceptive behaviors (flinching and licking/lifting) followed by long-term tactile secondary allodynia and hyperalgesia. Neither peripheral (into the formalin-injected paw) nor intrathecal morphine post-treatment reversed formalin-induced secondary allodynia and hyperalgesia. In contrast, morphine pre-treatment prevented the development of these pain behaviors. Intrathecal and peripheral post- but not pre-treatment with U-50488 or DADLE significantly reduced secondary allodynia and hyperalgesia. Interestingly, nociceptin reduced both pain behaviors regardless of the administration site or treatment time. Local antinociceptive effects of morphine, DADLE, U-50488 or nociceptin were blocked by naltrexone, naltrindole, 5-guanidinonaltrindole and [Nphe(1)]nociceptin(1-13)NH2, respectively. These results suggest that the long-term nociceptive behaviors induced by formalin are differentially modulated by selective opioid receptor agonists. In addition, data suggest that peripheral and spinal delta and kappa opioid receptors are important when nociceptive behaviors are established. In contrast, mu opioid receptors are more important at the beginning of the injury when the sensory system has not changed. NOP receptors participate diminishing both the development and maintenance of nociceptive behaviors. Results suggest that a barrage of afferent input induced by formalin injection initiates a long-term differential change in peripheral and spinal processing that affect the efficacy of opioid receptor agonists. (C) 2009 Elsevier B.V. All rights reserved.