Effect of naltrexone on neuropathic pain in mice locally transfected with the mutant μ-opioid receptor gene in spinal cord.
Effect of naltrexone on neuropathic pain in mice locally transfected with the mutant μ-opioid receptor gene in spinal cord.
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纳曲酮对脊髓局部转染突变型μ-阿片受体基因的小鼠神经性疼痛的影响。
DOI：
10.1111/bph.12790
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发表时间：
2015
影响因子：
7.3
通讯作者：
Tao,Pao-Luh
中科院分区：
文献类型：
--
作者：
Kao,Jen-Hsin;Gao,Man-Jun;Yang,Pao-Pao;Law,Ping-Yee;Loh,HoraceH;Tao,Pao-Luh
背景和目的阿片拮抗剂，如纳洛酮和纳曲酮，对突变的μ受体MOR - S196ACSTA表现出激动作用。在我们之前的研究中，在鞘内给药双链腺相关病毒- MOR - S196ACSTA - eGFP 2周后，全身纳洛酮（10mg·kg - 1, s.c）引起了抗伤害性作用，但没有诱导耐受性、依赖性或奖励效应。在这里，我们研究了这种抗感觉范式在神经性疼痛的小鼠模型中是否有效。实验方法在雄性C57BL/6小鼠鞘内注射编码MOR‐S196ACSTA‐eGFP结构的慢病毒（LV‐MOR‐S196ACSTA） 3或4周后结扎脊髓神经。通过von Frey试验评估每日s.c注射生理盐水、纳曲酮（10mg·kg−1）或吗啡（10mg·kg−1）的抗异动作用。经生理盐水、纳曲酮或吗啡治疗14天后，于最后一次注射后22和46小时测量自然戒断迹象。为了确定吗啡或纳曲酮诱导的奖励效应，采用条件位置偏好试验。von Frey试验显示，脊髓中转染LV - MOR - S196ACSTA的小鼠在纳曲酮或吗啡治疗后抗异动作用增强。停止吗啡治疗，而不是纳曲酮，诱导自然戒断和奖励效应。结论和意义在脊髓中表达突变的μ阿片受体MOR - S196ACSTA后全身注射纳曲酮可能具有治疗慢性神经性疼痛的潜力，而不会产生依赖性或成瘾性。本文是阿片类药物主题部分的一部分：功能选择性的新途径。要查看本节中的其他文章，请访问http://dx.doi.org/10.1111/bph.2015.172.issue-2
Background and PurposeOpioid antagonists, such as naloxone and naltrexone, exhibit agonistic properties at the mutated μ receptor, MOR‐S196ACSTA. In our previous study, systemic naloxone (10 mg·kg−1, s.c.) elicited antinociceptive effect without the induction of tolerance, dependence or rewarding effect in mice 2 weeks after intrathecal administration of double‐stranded adeno‐associated virus‐MOR‐S196ACSTA‐eGFP. Here, we have investigated if this antinociceptive paradigm would be effective in a mouse model of neuropathic pain.Experimental ApproachSpinal nerves were ligated in male C57BL/6 mice 3 or 4 weeks after intrathecal injection of the lentivirus encoding the construct of MOR‐S196ACSTA‐eGFP (LV‐MOR‐S196ACSTA). Anti‐allodynic effects of daily s.c.injections of saline, naltrexone (10 mg·kg−1) or morphine (10 mg·kg−1) were assessed by the von Frey test. After 14 days of treatment with saline, naltrexone or morphine, signs of natural withdrawal were measured at 22 and 46 h after the last injection. To determine the rewarding effects induced by morphine or naltrexone, the conditioned place preference test was carried out.Key ResultsAnti‐allodynic effects, as measured by von Frey test, increased after naltrexone or morphine treatment in mice transfected with LV‐MOR‐S196ACSTA in the spinal cord. Cessation of treatment with morphine, but not naltrexone, induced natural withdrawal and rewarding effects.Conclusions and ImplicationsSystemic injection of naltrexone after the expression of a mutant μ opioid receptor, MOR‐S196ACSTA, in the spinal cord may have therapeutic potential for chronic neuropathic pain, without the development of dependence or addiction.Linked ArticlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
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影响因子：
--
作者：
KATOW, H;SOLURSH, M
通讯作者：
SOLURSH, M
形态发生和海胆发育的细胞基础。
DOI：
10.1016/s0074-7696(08)61117-1
发表时间：
1963
期刊：
International review of cytology
影响因子：
--
作者：
T. Gustafson;L. Wolpert
通讯作者：
L. Wolpert
腹主动脉和下腔静脉结扎后血液中二氧化碳和氧气的含量
DOI：
10.3181/00379727-10-109
发表时间：
1913
影响因子：
--
作者：
J. Murlin;L. Edelmann;R. Giles
通讯作者：
R. Giles
DOI：
10.1083/jcb.41.1.227
发表时间：
1969-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Tilney LG;Gibbins JR
通讯作者：
Gibbins JR
海胆胚胎基底层的个体发育。
影响因子：
2.7
作者：
Wessel,GM;Marchase,RB;McClay,DR
通讯作者：
McClay,DR