Differential effects of opioid-related ligands and NSAIDs in nonhuman primate models of acute and inflammatory pain.
Differential effects of opioid-related ligands and NSAIDs in nonhuman primate models of acute and inflammatory pain.
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DOI：
10.1007/s00213-013-3341-0
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发表时间：
2014-04
影响因子：
3.4
通讯作者：
Ko, Mei-Chuan
中科院分区：
文献类型：
--
作者：
Sukhtankar, Devki D.;Lee, Heeseung;Rice, Kenner C.;Ko, Mei-Chuan
关键词：
角叉菜胶致痛敏是一种广泛应用于啮齿类动物的疼痛模型。然而，在非人类灵长类动物中，卡拉胶引起的痛敏反应的特征以及在这些条件下止痛药物的效果尚不清楚。本研究的目的是建立角叉菜胶诱导的恒河猴痛敏模型，并与非甾体抗炎药比较，确定在该模型中选择四种阿片受体亚型的激动剂对急性疼痛的疗效和效力。尾部注射角叉菜胶会在猴子身上产生持久的热痛敏。全身应用阿片受体激动剂芬太尼(MU/MOP)、U-50488H(KAPPA/KOP)、SNC80(Delta/DOP)和Ro-6198(伤害素/孤儿FQ/NOP)可剂量依赖性地减弱角叉菜胶热痛敏。在没有角叉菜胶的情况下，除SNC80外，这些激动剂均可阻断急性热伤害性感受。阿片类相关配体，尤其是Ro-6198，其抗痛敏作用远强于抗伤害感受作用。这两种作用都是由相应的受体机制介导的。只有芬太尼在止痛和止痛剂量下产生抓挠，与其对人类的瘙痒作用一致，这说明了MOP激动剂在非人类灵长类动物中的翻译图谱。与SNC80相似，全身应用非甾体类抗炎药酮咯酸和萘普生可剂量依赖性地减轻卡拉胶引起的痛敏，但不能减轻急性痛觉。在非人类灵长类动物中使用两种不同的止痛方式，比较了临床上可用的镇痛剂如芬太尼、酮咯酸和萘普生的有效性，并与选择性KOP、DOP和NOP激动剂进行了比较。阿片类相关配体在调节同一受试者的痛觉过敏和急性伤害性感受方面表现出不同的药理学特性。这种临床前灵长类动物模型可用于研究新型止痛药。
Carrageenan-induced hyperalgesia is a widely used pain model in rodents. However, characteristics of carrageenan-induced hyperalgesia and effects of analgesic drugs under these conditions are unknown in nonhuman primates. The aims of this study were to develop carrageenan-induced hyperalgesia in rhesus monkeys and determine the efficacy and potency of agonists selective for the four opioid receptor subtypes in this model versus acute pain, as compared to NSAIDs. Tail-injection of carrageenan produced long-lasting thermal hyperalgesia in monkeys. Systemically administered agonists selective for opioid receptor subtypes i.e. fentanyl (mu/MOP), U-50488H (kappa/KOP), SNC80 (delta/DOP) and Ro 64-6198 (nociceptin/orphanin FQ/NOP) dose-dependently attenuated carrageenan-induced thermal hyperalgesia with different potencies. In absence of carrageenan, these agonists, except SNC80, blocked acute thermal nociception. Opioid-related ligands, especially Ro 64-6198, were much more potent for their antihyperalgesic than antinociceptive effects. Both effects were mediated by the corresponding receptor mechanisms. Only fentanyl produced scratching at antihyperalgesic and antinociceptive doses consistent with its pruritic effects in humans, illustrating a translational profile of MOP agonists in nonhuman primates. Similar to SNC80, systemically administered NSAIDs ketorolac and naproxen dose-dependently attenuated carrageenan-induced hyperalgesia but not acute nociception. Using two different pain modalities in nonhuman primates, effectiveness of clinically available analgesics like fentanyl, ketorolac and naproxen was distinguished and their efficacies and potencies were compared with the selective KOP, DOP, and NOP agonists. The opioid-related ligands displayed differential pharmacological properties in regulating hyperalgesia and acute nociception in the same subjects. Such preclinical primate models can be used to investigate novel analgesic agents.
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影响因子：
7.3
作者：
BARBER, A;BARTOSZYK, GD;SEYFRIED, CA
通讯作者：
SEYFRIED, CA
DOI：
10.1124/jpet.111.189902
发表时间：
2012-05-01
影响因子：
3.5
作者：
Bianchi, Bruce R.;Zhang, Xu-Feng;Chen, Jun
通讯作者：
Chen, Jun
DOI：
10.1124/jpet.103.052381
发表时间：
2003-09-01
影响因子：
3.5
作者：
Butelman, ER;Ball, JW;Kreek, MJ
通讯作者：
Kreek, MJ
影响因子：
2.9
作者：
Itoh, M;Takasaki, I;Kuraishi, Y
通讯作者：
Kuraishi, Y
影响因子：
8.8
作者：
ELLIS, DJ;MILLAR, WL;REISNER, LS
通讯作者：
REISNER, LS