UPREGULATION OF PRONOCICEPTIVE MEDIATORS AND DOWNREGULATION OF OPIOID PEPTIDE BY ADRENOMEDULLIN FOLLOWING CHRONIC EXPOSURE TO MORPHINE IN RATS
UPREGULATION OF PRONOCICEPTIVE MEDIATORS AND DOWNREGULATION OF OPIOID PEPTIDE BY ADRENOMEDULLIN FOLLOWING CHRONIC EXPOSURE TO MORPHINE IN RATS
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大鼠长期暴露于吗啡后肾上腺髓质素对促感受介质的上调和阿片肽的下调
DOI：
10.1016/j.neuroscience.2014.08.048
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发表时间：
2014-11
期刊：
影响因子：
3.3
通讯作者：
Hong Y.
中科院分区：
文献类型：
--
作者：
Wang D.;Li J.;Chen P.;Hong Y.
肾上腺髓质素 (AM) 属于降钙素基因相关肽 (CGRP) 家族，已被证明在炎症中长期使用吗啡和神经元一氧化氮合酶 (nNOS) 后可募集 CGRP。本研究调查了 AM 引发其他分子变化的可能性，这些变化有助于长期使用吗啡耐受性的发展。鞘内 (i.t.) 共同施用 AM 受体拮抗剂 AM22–52（35.8 μg）会抑制对吗啡诱导的镇痛的耐受性，而每日注射 AM 受体激动剂 AM1–50（8 μg，i.t.，推注）9 天会导致吗啡镇痛和热痛觉过敏的效力下降。培养的背根神经节 (DRG) 外植体持续暴露于吗啡 (3.3 μM) 4 天，导致 AM 和 CGRP mRNA 水平增加。然而，吗啡在 AM22–52(2 µM) 存在的情况下无法产生这些效果。它。给予吗啡 6 天增加了脊髓背角和 DRG 神经元中 nNOS 的表达，但降低了 DRG 中小型神经元中内源性阿片肽牛肾上腺髓质 22 (BAM22) 的表达。特别是，联合施用 AM22–52（35.8 μg）可抑制吗啡诱导的 nNOS 和 BAM22 变化。这些结果表明，nNOS和CGRP表达的增加以及BAM22的减少归因于慢性吗啡诱导的AM受体信号传导增加。本研究支持这样的假设：AM 生物活性的增强引发了促伤害感受介质的上调和疼痛抑制分子的下调，从而促进吗啡耐受的发展。
Adrenomedullin (AM) belongs to a calcitonin gene-related peptide (CGRP) family and has been demonstrated to recruit CGRP following chronic use of morphine and neuronal nitric oxide synthase (nNOS) in inflammation. The present study investigated the possibility that AM initiates the changes of other molecules contributing to the development of morphine tolerance in its chronic use. Intrathecal (i.t.) co-administration of the AM receptor antagonist AM22–52(35.8 μg) inhibited tolerance to morphine-induced analgesia while a daily injection of the AM receptor agonist AM1–50(8 μg, i.t., bolus) for 9 days induced a decrease in the potency of morphine analgesia and thermal hyperalgesia. Persistent exposure of cultured dorsal root ganglion (DRG) explants to morphine (3.3 μM) for 4 days resulted in an increase in AM and CGRP mRNA levels. However, morphine failed to produce these effects in the presence of AM22–52(2 μM). The i.t. administration of morphine for 6 days increased the expression of nNOS in the spinal dorsal horn and DRG neurons but decreased expression of the endogenous opioid peptide bovine adrenal medulla 22 (BAM22) in small- and medium-sized neurons in DRG. Particularly, the co-administration of AM22–52(35.8 μg) inhibited the morphine-induced alterations in nNOS and BAM22. These results indicated that the increase in nNOS and CGRP expressions and the decrease in BAM22 were attributed to the increased AM receptor signaling induced by chronic morphine. The present study supports the hypothesis that the enhancement of AM bioactivity triggered upregulation of pronociceptive mediators and downregulation of pain-inhibiting molecule in a cascade contributing to the development of morphine tolerance.
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影响因子：
6.1
作者：
R. Przewłocki;H. Machelska;B. Przewłocka
通讯作者：
R. Przewłocki;H. Machelska;B. Przewłocka
影响因子：
4.7
作者：
Toyohiro Fujita;Y. Kamisaki;N. Yonehara
通讯作者：
Toyohiro Fujita;Y. Kamisaki;N. Yonehara
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
影响因子：
7.3
作者：
Hong, YG;Dai, PF;Zeng, XA
通讯作者：
Zeng, XA
影响因子：
3
作者：
Bhargava, HN;Cao, YJ;Zhao, GM
通讯作者：
Zhao, GM