Evaluation of the effects of specific opioid receptor agonists in a rodent model of spinal cord injury.
Evaluation of the effects of specific opioid receptor agonists in a rodent model of spinal cord injury.
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DOI：
10.1038/sc.2016.28
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发表时间：
2016-10
期刊：
影响因子：
2.2
通讯作者：
Hook, M. A.
中科院分区：
文献类型：
--
作者：
Aceves, M.;Mathai, B. B.;Hook, M. A.
目前的研究旨在评估特定阿片受体系统对吗啡镇痛和有害作用的贡献，在先前的研究中观察到脊髓损伤后。我们使用特异性阿片受体激动剂来评估μ-（DAMGO）、δ-（DPDPE）和κ-（GR 89696）阿片受体激活对啮齿动物挫伤模型（T12）中运动（BBB、锥形梁、梯形试验）和感觉（腰带、触觉和甩尾试验）恢复的影响。我们还使用[+]-吗啡测试了非经典阿片类药物结合的贡献。首先，生成每种阿片类激动剂的镇痛功效的剂量-反应曲线。损伤后24小时评估基线运动和感觉反应性。受试者，然后治疗与鞘内剂量的特定激动剂和重新测试后30分钟。为了评估对恢复的影响，受试者进行了治疗与单剂量的激动剂和运动和感觉功能进行了监测21天。除了[+]-吗啡对映体以外，所有经典阿片受体激动剂在相当于先前显示产生强镇痛作用的吗啡剂量（0.32 μmol）的浓度下产生抗伤害感受。DAMGO和[+]-吗啡不影响长期恢复。然而，在所有测试剂量下，GR 89696显著破坏运动功能的恢复。基于这些数据，我们假设吗啡的镇痛作用主要是通过与经典的μ-阿片受体结合来介导的。相反，吗啡的副作用可能与κ-阿片受体的激活有关。最终，阐明吗啡作用的分子机制是必要的，以便在临床环境中开发安全有效的药理学干预措施。美国
The current study aimed to evaluate the contribution(s) of specific opioid receptor systems to the analgesic and detrimental effects of morphine, observed after spinal cord injury in prior studies. We used specific opioid receptor agonists to assess the effects of µ- (DAMGO), δ- (DPDPE), and κ- (GR89696) opioid receptor activation on locomotor (BBB, tapered beam, ladder tests) and sensory (girdle, tactile, and tail-flick tests) recovery in a rodent contusion model (T12). We also tested the contribution of non-classic opioid binding using [+]- morphine. First, a dose-response curve for analgesic efficacy was generated for each opioid agonist. Baseline locomotor and sensory reactivity was assessed 24 h after injury. Subjects were then treated with an intrathecal dose of a specific agonist and re-tested after 30 min. To evaluate effects on recovery, subjects were treated with a single dose of an agonist and both locomotor and sensory function were monitored for 21 d. All agonists for the classic opioid receptors, but not the [+]- morphine enantiomer, produced antinociception at a concentration equivalent to a dose of morphine previously shown to produce strong analgesic effects (0.32 μmol). DAMGO and [+]- morphine did not affect long-term recovery. GR89696, however, significantly undermined recovery of locomotor function at all doses tested. Based on these data, we hypothesize that the analgesic efficacy of morphine is primarily mediated by binding to the classic μ-opioid receptor. Conversely, the adverse effects of morphine may be linked to activation of the κ-opioid receptor. Ultimately, elucidating the molecular mechanisms underlying the effects of morphine is imperative in order to develop safe and effective pharmacological interventions in a clinical setting. USA
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影响因子：
15.1
作者：
Hutchinson, Mark R.;Zhang, Yingning;Shridhar, Mitesh;Evans, John H.;Buchanan, Madison M.;Zhao, Tina X.;Slivka, Peter F.;Coats, Benjamen D.;Rezvani, Niloofar;Wieseler, Julie;Hughes, Travis S.;Landgraf, Kyle E.;Chan, Stefanie;Fong, Stephanie;Phipps, Simon;Falke, Joseph J.;Leinwand, Leslie A.;Maier, Steven F.;Yin, Hang;Rice, Kenner C.;Watkins, Linda R.
通讯作者：
Watkins, Linda R.
影响因子：
2.7
作者：
Hook, Michelle A.;Liu, Grace T.;Grau, James W.
通讯作者：
Grau, James W.
影响因子：
2.9
作者：
Cui, Y;Chen, Y;Chen, PX
通讯作者：
Chen, PX
影响因子：
4.2
作者：
Christensen, MD;Hulsebosch, CE
通讯作者：
Hulsebosch, CE
影响因子：
4.2
作者：
Ferguson, AR;Hook, MA;Grau, JW
通讯作者：
Grau, JW