Adenosine-A1 receptor agonist induced hyperalgesic priming type II.
Adenosine-A1 receptor agonist induced hyperalgesic priming type II.
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DOI：
10.1097/j.pain.0000000000000421
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发表时间：
2016-03
期刊：
影响因子：
7.4
通讯作者：
Levine JD
中科院分区：
文献类型：
--
作者：
Araldi D;Ferrari LF;Levine JD
我们最近发现，初级传入伤害感受器的外周末端反复暴露于 mu-阿片受体 (MOR) 激动剂 DAMGO（[D-Ala2、N-Me-Phe4、Gly5-ol]-脑啡肽醋酸盐）会诱导向慢性疼痛转变的模型，我们将其称为 II 型痛觉过敏引发。与 I 型痛觉过敏启动类似，随后给予促痛细胞因子，典型的前列腺素 E2 (PGE2)，反应显着延长。然而，II 型痛觉过敏引发与 I 型的不同之处在于，II 型痛觉过敏引发快速诱导，依赖于蛋白激酶 A (PKA)，而不是 PKCε，不会被蛋白质翻译抑制剂逆转，发生在雌性和雄性大鼠中，并且依赖于异凝集素 B4 阴性神经元。我们报告说，与重复注射 MOR 激动剂一样，在 A1-腺苷受体（也是一种 Gi 蛋白偶联受体）N6-环戊基腺苷 (CPA) 上重复注射激动剂也会产生类似于 DAMGO 诱导的 II 型痛觉过敏启动的启动。在本研究中，我们证明反复暴露于这种 A1-腺苷受体激动剂诱导的启动与 MOR 激动剂诱导的启动具有相同的机制。然而，重复给予CPA诱导的PGE2痛觉过敏的延长取决于G蛋白αi亚基的激活，这与DAMGO诱导的II型启动不同，后者取决于β/γ亚基。这些数据暗示了 II 型痛觉过敏启动中存在一种新形式的 Gi 蛋白信号传导途径，该启动是通过向伤害感受器的外周末端重复施用 A1-腺苷受体激动剂而诱导的。
We have recently shown that repeated exposure of the peripheral terminal of the primary afferent nociceptor to the mu-opioid receptor (MOR) agonist DAMGO ([D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin acetate salt) induces a model of the transition to chronic pain that we have termed Type II hyperalgesic priming. Similar to Type I hyperalgesic priming, there is a markedly prolonged response to subsequent administration of proalgesic cytokines, prototypically prostaglandin E2 (PGE2). However, Type II hyperalgesic priming differs from Type I in being rapidly induced, protein kinase A (PKA), rather than PKCε dependent, not reversed by a protein translation inhibitor, occurring in female as well as in male rats, and isolectin B4-negative neuron dependent. We report that as with the repeated injection of a MOR agonist, the repeated administration of an agonist at the A1-adenosine receptor, also a Gi-protein coupled receptor, N6-Cyclopentyladenosine (CPA), also produces priming similar to DAMGO-induced Type II hyperalgesic priming. In this study we demonstrate that priming induced by repeated exposure to this A1-adenosine receptor agonist shares the same mechanisms as MOR-agonist induced priming. However, the prolongation of PGE2 hyperalgesia induced by repeated administration of CPA depends on G-protein αi subunit activation, differently from DAMGO-induced Type II priming, in which it depends on the β/γ subunit. These data implicate a novel form of Gi-protein signaling pathway in the Type II hyperalgesic priming induced by repeated administration of an agonist at A1-adenosine receptor to the peripheral terminal of the nociceptor.
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DOI：
10.1523/jneurosci.5138-11.2012
发表时间：
2012-02-08
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bogen O;Alessandri-Haber N;Chu C;Gear RW;Levine JD
通讯作者：
Levine JD
影响因子：
4
作者：
Ferrari, Luiz F.;Levine, Jon D.
通讯作者：
Levine, Jon D.
DOI：
10.1523/jneurosci.4346-09.2010
发表时间：
2010-01-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
Chen Y;Yang C;Wang ZJ
通讯作者：
Wang ZJ
影响因子：
5.3
作者：
Ferrari, Luiz F.;Bogen, Oliver;Levine, Jon D.
通讯作者：
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Gi 的激活会诱发应激后机械痛觉过敏或炎症。
影响因子：
3.3
作者：
Dina, O. A.;Khasar, S. G.;Gear, R. W.;Levine, J. D.
通讯作者：
Levine, J. D.