Peripheral antinociceptive effects of μ- and δ-opioid receptor agonists in NOS2 and NOS1 knockout mice during chronic inflammatory pain
Peripheral antinociceptive effects of μ- and δ-opioid receptor agonists in NOS2 and NOS1 knockout mice during chronic inflammatory pain
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DOI：
10.1016/j.ejphar.2008.11.019
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发表时间：
2009-01-05
影响因子：
5
通讯作者：
Pol, Olga
中科院分区：
文献类型：
--
作者：
Leanez, Sergi;Hervera, Arnau;Pol, Olga
本研究的目的是探讨诱导型（NOS2）或神经元型（NOS1）一氧化氮合酶合成的一氧化氮是否参与慢性炎性疼痛中阿片受体激动剂和阿片受体激动剂产生的局部抗痛觉作用。在NOS2和NOS1基因敲除小鼠及其野生型仔鼠足底下给药完全弗氏佐剂（30 μ l）诱导外周炎性疼痛。分别通过测量足部直径、von Frey纤维和足底试验来评估完全弗氏佐剂引起的足部炎症、机械性异常痛和热痛感过敏的存在。在慢性炎症期间，与野生型相比，NOS2缺失小鼠脚掌水肿恢复更快，热痛觉过敏减轻。相比之下，与野生型相比，NOS1基因敲除小鼠的足部水肿和机械异常性疼痛减轻，并且从热痛觉过敏中适度快速恢复。NOS2基因敲除小鼠足底下注射吗啡（第4天和第7天）或[D-Pen(2.5)]脑啡肽（DPDPE）（第1天和第4天）不能完全逆转完全弗氏佐剂诱导的热痛感过敏。此外，局部给药吗啡或DPDPE也未能逆转NOS1敲除小鼠在10天的外周炎症中完全弗氏佐剂引起的同侧足爪戒断潜伏期的减少。这些结果提示NOS2和NOS1合成的一氧化氮在维持慢性炎性疼痛引起的机械性异位痛和热痛觉过敏中所起的不同作用，以及在炎性疼痛期间mu-和delta-阿片受体激动剂产生的抗痛觉作用中所起的不同作用。(C) 2008 Elsevier B.V.版权所有
The aim of this study is to investigate the involvement of nitric oxide synthesized by the inducible (NOS2) or neuronal (NOS1) nitric oxide synthases in the local antinociceptive effects produced by mu- and delta-opioid receptor agonists during chronic inflammatory pain. Peripheral inflammatory pain was induced in NOS2 and NOS1 knockout mice and their wild type littermates by the subplantar administration of complete Freund's adjuvant (30 mu l). The presence of paw inflammation, mechanical allodynia and thermal hyperalgesia induced by complete Freund's adjuvant were assessed by measuring paw diameter and using the von Frey filaments and plantar tests, respectively. During chronic inflammation, NOS2 deficient mice have a more rapid recovery of paw edema and a reduced thermal hyperalgesia compared to wild type. In contrast, a reduced paw edema and mechanical allodynia, as well as a modest rapid recovery from thermal hyperalgesia were observed in NOS1 knockout mice compared to wild type. The thermal hyperalgesia induced by complete Freund's adjuvant was not completely reversed by the subplantar administration of morphine (days 4 and 7) or [D-Pen (2.5)] enkephalin (DPDPE) (days 1 and 4) in NOS2 knockout mice as occurs in wild type mice. Moreover, the local administration of morphine or DPDPE also failed to reverse the decrease of ipsilateral paw withdrawal latency induced by complete Freund's adjuvant in NOS1 knockout mice throughout 10 days of peripheral inflammation. These results indicate the different roles played by nitric oxide synthesized by NOS2 or NOS1 in the maintenance of mechanical allodynia and thermal hyperalgesia induced by chronic inflammatory pain as well as, in the antinociceptive effects produced by mu- and delta-opioid receptor agonists during peripheral inflammatory pain. (C) 2008 Elsevier B.V. All rights reserved.