Spinal and Peripheral Mechanisms Involved in the Enhancement of Morphine Analgesia in Acutely Inflamed Mice
Spinal and Peripheral Mechanisms Involved in the Enhancement of Morphine Analgesia in Acutely Inflamed Mice
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DOI：
10.1007/s10571-009-9436-9
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Menendez, Luis
中科院分区：
文献类型：
--
作者：
Gonzalez-Rodriguez, Sara;Hidalgo, Agustin;Menendez, Luis
在实验性炎症过程中，阿片类药物诱导的镇痛作用常常增强。我们在这里描述，较低剂量的全身吗啡是必要的，以增加热戒断lasting测量在两个后爪的小鼠与角叉菜胶急性发炎比健康的。这种双侧增强似乎是通过脊髓阿片受体介导的，因为它被鞘内（i.t.）而不是足底内（i.pl.）阿片样物质受体拮抗剂纳洛酮-甲碘化物的给药，并且当吗啡是i.t.管理。此外，i.pl.向角叉菜胶发炎的小鼠施用一氧化氮（NO）合酶抑制剂1-NMMA或K（ATP）（+）-通道阻断剂格列本脲抑制了接受药物注射的爪中全身吗啡的增强作用，而不影响在对侧爪中观察到的增强作用。i.pl.给予l-NMMA也部分拮抗i.t.吗啡在发炎的老鼠身上。最后，增加镇痛效果诱发的i. pl.在角叉菜胶发炎小鼠的发炎或对侧爪中施用NO供体SIN-1表明，对NO的外周镇痛作用的增强的反应性也可能是急性发炎小鼠中吗啡诱导的镇痛的双侧增强的基础。
The analgesic effect induced by opiates is often potentiated during experimental inflammatory processes. We describe here that lower doses of systemic morphine are necessary to increase thermal withdrawal latencies measured in both hind paws of mice acutely inflamed with carrageenan than in healthy ones. This bilateral potentiation seems mediated through spinal opioid receptors since it is inhibited by the intrathecal (i.t.), but not intraplantar (i.pl.) administration of the opioid receptor antagonist naloxone-methiodide, and also appears when morphine is i.t. administered. Furthermore, the i.pl. administration of the nitric oxide (NO) synthase inhibitor, l-NMMA, or the K (ATP) (+) -channel blocker, glibenclamide, to carrageenan-inflamed mice inhibits the enhanced effect of systemic morphine in the paw that receives the injection of the drug, without affecting the potentiation observed in the contralateral one. The i.pl. administration of l-NMMA also partially antagonised the analgesic effect induced by i.t. morphine in inflamed mice. Finally, the increased analgesic effect evoked by the i.pl. administration of the NO donor SIN-1 either in the inflamed or in the contralateral paw of carrageenan-inflamed mice suggests that enhanced responsiveness to the peripheral analgesic effect of NO may be also underlying the bilateral potentiation of morphine-induced analgesia in acutely inflamed mice.