Acute thermal hyperalgesia elicited by low-dose morphine in normal mice is blocked by ultra-low-dose naltrexone, unmasking potent opioid analgesia
Acute thermal hyperalgesia elicited by low-dose morphine in normal mice is blocked by ultra-low-dose naltrexone, unmasking potent opioid analgesia
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DOI：
10.1016/s0006-8993(00)03010-9
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发表时间：
2001-01-05
期刊：
影响因子：
2.9
通讯作者：
Shen, KF
中科院分区：
文献类型：
--
作者：
Crain, SM;Shen, KF
我们之前对培养的背根神经节（DRG）神经元的伤害性类型的电生理学研究表明，极低的fM-nM浓度的吗啡和许多其他双峰作用的mu， delta和kappa阿片受体激动剂可以引起直接的兴奋性阿片受体介导的作用，而较高的（muM）阿片受体浓度则引起抑制作用。pM纳洛酮或纳曲酮（NTX）与fM-nM吗啡联合治疗阻断了这些低阿片类药物浓度的兴奋作用，并揭示了这些低阿片类药物浓度的有效抑制作用。在目前的研究中，在52度的温度下对小鼠进行热水浸尾厚抗痛觉试验表明，极低剂量的吗啡（约0.1杯/公斤）实际上可以引起急性痛觉过敏作用。表现为给药后快速开始的甩尾潜伏期减少，持续时间为3 ~ 3小时。与超低剂量NTX（约1-100 pp/kg）联合治疗可阻断这种阿片类药物引起的痛觉过敏，并揭示有效的阿片类药物镇痛作用。体外和体内证据的一致性表明，当阿片样物质的过敏效应被适当低剂量的阿片样物质拮抗剂阻断时，远低于目前临床治疗疼痛所需的吗啡剂量可能会有效。这种低剂量吗啡联合治疗程序应显著减弱吗啡耐受性、依赖性和其他不良副作用。(C) 2001 Elsevier Science B.V.版权所有
Our previous electrophysiologic studies on nociceptive types of dorsal root ganglion (DRG) neurons in culture demonstrated that extremely low fM-nM concentrations of morphine and many other bimodally-acting mu, delta and kappa opioid agonists can elicit direct excitatory opioid receptor-mediated effects, whereas higher (muM) opioid concentrations evoked inhibitory effects. Cotreatment with pM naloxone or naltrexone (NTX) plus fM-nM morphine blocked the excitatory effects and unmasked potent inhibitory effects of these low opioid concentrations. In the present study, hot-water-immersion tail-hick antinociception assays at 52 degreesC on mice showed that extremely low doses of morphine (ca. 0.1 mug/kg) can, in fact, elicit acute hyperalgesic effects. manifested by rapid onset of decreases in tail-flick latency for periods >3 h after drug administration. Cotreatment with ultra-low-dose NTX (ca. 1-100 pp/kg) blocks this opioid-induced hyperalgesia and unmasks potent opioid analgesia. The consonance of our in vitro and in vivo evidence indicates that doses of morphine far below those currently required for clinical treatment of pain may become effective when opioid hyperalgesic effects are blocked by coadministration of appropriately low doses of opioid antagonists. This low-dose-morphine cotreatment procedure should markedly attenuate morphine tolerance, dependence and other aversive side-effects. (C) 2001 Elsevier Science B.V. All rights reserved.