Delta-opioid receptor analgesia is independent of microglial activation in a rat model of neuropathic pain.
Delta-opioid receptor analgesia is independent of microglial activation in a rat model of neuropathic pain.
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DOI：
10.1371/journal.pone.0104420
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Przewlocka B
中科院分区：
文献类型：
--
作者：
Mika J;Popiolek-Barczyk K;Rojewska E;Makuch W;Starowicz K;Przewlocka B
δ-阿片受体（DOR）配体在神经性疼痛中的镇痛作用与其他阿片受体配体相比没有减弱，所述其他阿片受体配体失去其作为镇痛剂的有效性。在这项研究中，我们研究了这种效应是否与神经损伤诱导的小胶质细胞激活有关。因此，我们研究了米诺环素诱导的抑制小胶质细胞活化对阿片受体激动剂吗啡，DAMGO，U 50，488 H，DPDPE，Deltorphin II和SNC 80在大鼠坐骨神经慢性压迫性损伤（CCI）后的镇痛作用的影响。预先和重复施用米诺环素（30 mg/kg，i. p.）如CCI后第7天所测量的，超过7天显著降低了异常性疼痛和痛觉过敏。鞘内（i.t.）二甲胺四环素后，大鼠给予吗啡（10-20 μg）、DAMGO（1-2 μg）和U 50，488 H（25-50 μg）后，显著增强，但给予DPDPE（10-20 μg）、deltorphin II（1.5-15 μg）和SNC 80（10-20 μg）后，未观察到此类变化。此外，神经损伤诱导的脊髓和背根神经节中所有类型阿片受体的下调不受米诺环素的影响，这表明阿片配体的作用依赖于其他变化，可能是神经免疫相互作用。我们使用qRT-PCR、蛋白质印迹和免疫细胞化学对大鼠原代小胶质细胞培养的研究证实了μ-阿片受体（莫尔）和κ-阿片受体（KOR）的存在，进一步我们提供了小胶质细胞上缺乏DOR的第一个证据。总之，DOR镇痛不同于由莫尔和KOR受体诱导的镇痛，因为它不依赖于损伤诱导的小胶质细胞活化。DOR激动剂似乎是治疗神经性疼痛的新药的最佳候选者。
The analgesic effect of delta-opioid receptor (DOR) ligands in neuropathic pain is not diminished in contrast to other opioid receptor ligands, which lose their effectiveness as analgesics. In this study, we examine whether this effect is related to nerve injury-induced microglial activation. We therefore investigated the influence of minocycline-induced inhibition of microglial activation on the analgesic effects of opioid receptor agonists: morphine, DAMGO, U50,488H, DPDPE, Deltorphin II and SNC80 after chronic constriction injury (CCI) to the sciatic nerve in rats. Pre-emptive and repeated administration of minocycline (30 mg/kg, i.p.) over 7 days significantly reduced allodynia and hyperalgesia as measured on day 7 after CCI. The antiallodynic and antihyperalgesic effects of intrathecally (i.t.) administered morphine (10–20 µg), DAMGO (1–2 µg) and U50,488H (25–50 µg) were significantly potentiated in rats after minocycline, but no such changes were observed after DPDPE (10–20 µg), deltorphin II (1.5–15 µg) and SNC80 (10–20 µg) administration. Additionally, nerve injury-induced down-regulation of all types of opioid receptors in the spinal cord and dorsal root ganglia was not influenced by minocycline, which indicates that the effects of opioid ligands are dependent on other changes, presumably neuroimmune interactions. Our study of rat primary microglial cell culture using qRT-PCR, Western blotting and immunocytochemistry confirmed the presence of mu-opioid receptors (MOR) and kappa-opioid receptors (KOR), further we provide the first evidence for the lack of DOR on microglial cells. In summary, DOR analgesia is different from analgesia induced by MOR and KOR receptors because it does not dependent on injury-induced microglial activation. DOR agonists appear to be the best candidates for new drugs to treat neuropathic pain.
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影响因子：
1.6
作者：
Gavériaux-Ruff C;Kieffer BL
通讯作者：
Kieffer BL
DOI：
10.1097/qad.0b013e3283639804
发表时间：
2013-09-10
期刊：
AIDS (London, England)
影响因子：
--
作者：
El-Hage N;Dever SM;Podhaizer EM;Arnatt CK;Zhang Y;Hauser KF
通讯作者：
Hauser KF
影响因子：
5.3
作者：
Fillpovic, Radmila;Zecevic, Nada
通讯作者：
Zecevic, Nada
影响因子：
4.8
作者：
George, SR;Fan, T;O'Dowd, BF
通讯作者：
O'Dowd, BF
影响因子：
3.4
作者：
Gonzalez, Jose Carlos;Egea, Javier;Hernandez-Guijo, Jesus M.
通讯作者：
Hernandez-Guijo, Jesus M.