Blockade of adrenomedullin receptors reverses morphine tolerance and its neurochemical mechanisms
Blockade of adrenomedullin receptors reverses morphine tolerance and its neurochemical mechanisms
复制标题
阻断肾上腺髓质素受体可逆转吗啡耐受及其神经化学机制
DOI：
10.1016/j.bbr.2011.02.046
复制
发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Yanguo Hong
中科院分区：
文献类型：
--
作者：
Dongmei Wang;Peiwen Chen;Qi Li;Rémi Quirion;Yanguo Hong
肾上腺髓质素（AM）已被证明参与阿片耐受性的发展。本研究进一步探讨了AM在维持吗啡耐受、吗啡相关痛觉过敏中的作用及其细胞机制。鞘内注射吗啡6天后，镇痛效果下降，痛觉过敏。急性给药AM受体拮抗剂am22 - 52恢复吗啡效价呈剂量依赖性（12、35.8和71.5 μg, i.t）。am22 - 52治疗也抑制了吗啡耐受性相关的痛觉过敏。此外，给药35.8 μg的am22 - 52可逆转吗啡诱导的脊髓背角和/或背根神经节（DRG） nNOS（神经元一氧化氮合酶）和CGRP免疫反应性的增强。有趣的是，长期给药吗啡降低了内源性阿片肽牛肾上腺髓质22 （BAM22）在DRG中小神经元中的表达，这种减少被AM22-52 （35.8 μg）部分逆转。这些结果提示AM受体的激活不仅通过上调前感觉介质nNOS和CGRP，还通过下调疼痛抑制分子BAM22介导吗啡耐受的维持。我们的数据支持这一假设，即前感觉介质和内源性疼痛抑制分子的水平对吗啡镇痛的效力有影响。靶向AM受体是一种很有前途的方法，以维持吗啡镇痛效力在慢性使用这种药物。
Adrenomedullin (AM) has been demonstrated to be involved in the development of opioid tolerance. The present study further investigated the role of AM in the maintenance of morphine tolerance, morphine-associated hyperalgesia and its cellular mechanisms. Intrathecal (i.t.) injection of morphine for 6 days induced a decline of its analgesic effect and hyperalgesia. Acute administration of the AM receptor antagonist AM22–52resumed the potency of morphine in a dose-dependent manner (12, 35.8 and 71.5 μg, i.t.). The AM22–52treatment also suppressed morphine tolerance-associated hyperalgesia. Furthermore, i.t. administration of AM22–52at a dose of 35.8 μg reversed the morphine induced-enhancement of nNOS (neuronal nitric oxide synthase) and CGRP immunoreactivity in the spinal dorsal horn and/or dorsal root ganglia (DRG). Interestingly, chronic administration of morphine reduced the expression of the endogenous opioid peptide bovine adrenal medulla 22 (BAM22) in small- and medium-sized neurons in DRG and this reduction was partially reversed by the administration of AM22–52(35.8 μg). These results suggest that the activation of AM receptors was involved in the maintenance of morphine tolerance mediating by not only upregulation of the pronociceptive mediators, nNOS and CGRP but also the down-regulation of pain-inhibiting molecule BAM22. Our data support the hypothesis that the level of both pronociceptive mediators and endogenous pain-inhibiting molecules has an impact on the potency of morphine analgesia. Targeting AM receptors is a promising approach to maintain the potency of morphine analgesia during chronic use of this drug.
登录
查看更多内容
DOI：
--
发表时间：
1985-12
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
A. Dray;L. Nunan;W. Wire
通讯作者：
A. Dray;L. Nunan;W. Wire
影响因子：
7.3
作者：
Hong, YG;Dai, PF;Zeng, XA
通讯作者：
Zeng, XA
DOI：
10.1523/jneurosci.16-07-02342.1996
发表时间：
1996-04
期刊：
--
影响因子：
--
作者：
Daniel P M6nard;Denise Van Rossurn;S Kar;S. St;Pierre;M. Sutak;K. Jhamandas;R6mi Quirionl
通讯作者：
Daniel P M6nard;Denise Van Rossurn;S Kar;S. St;Pierre;M. Sutak;K. Jhamandas;R6mi Quirionl
DOI：
--
发表时间：
1995-05
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
D. Ménard;D. van Rossum;S. Kar;F. Jolicoeur;K. Jhamandas;R. Quirion
通讯作者：
D. Ménard;D. van Rossum;S. Kar;F. Jolicoeur;K. Jhamandas;R. Quirion
影响因子：
5.9
作者：
Chang, Grace;Chen, Lucy;Mao, Jianren
通讯作者：
Mao, Jianren