LIPOXIN A4 ANALOG ATTENUATES MORPHINE ANTINOCICEPTIVE TOLERANCE, WITHDRAWAL-INDUCED HYPERALGESIA, AND GLIAL REACTION AND CYTOKINE EXPRESSION IN THE SPINAL CORD OF RAT
LIPOXIN A4 ANALOG ATTENUATES MORPHINE ANTINOCICEPTIVE TOLERANCE, WITHDRAWAL-INDUCED HYPERALGESIA, AND GLIAL REACTION AND CYTOKINE EXPRESSION IN THE SPINAL CORD OF RAT
复制标题
DOI：
10.1016/j.neuroscience.2012.02.009
复制
发表时间：
2012-04-19
期刊：
影响因子：
3.3
通讯作者：
Bo, Y.
中科院分区：
文献类型：
--
作者：
Jin, H.;Li, Y. -H.;Bo, Y.
脊髓神经炎症在吗啡耐受和吗啡戒断痛敏的形成中起重要作用。脂氧素是内源性脂氧合酶衍生的类二十烷酸，可在炎症中起“制动信号”的作用。本研究观察了脂氧素A（4）的稳定合成类似物5（S），6（R）-脂氧素A（4）甲酯（LXA（4）ME）对慢性吗啡处理大鼠抗伤害性耐受和戒断痛敏表达的影响。慢性吗啡皮下注射可诱导痛敏的发生和脊髓抗伤害耐受的表达。然而，LXA（4）ME处理显著减弱了痛敏的发展和脊髓对鞘内吗啡的抗伤害性耐受的表达。此外，在吗啡耐受诱导过程中给予LXA（4）ME抑制了小胶质细胞和星形胶质细胞的活化，降低了促炎细胞因子白细胞介素-1 β的表达，（IL-1 β）、IL-6和肿瘤坏死因子-α（TNF-α）;上调抗炎细胞因子IL-10和转化生长因子β 1的表达（TGF-β 1）;并抑制L5腰髓的核因子-κ B（NF-κ B）活化。这些结果表明，LXA（4）ME的治疗为吗啡耐受和相关的异常疼痛敏感性提供了一种潜在的预防或治疗方法。(C)2012年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Spinal neuroinflammation has been shown to play an important role in the development of morphine tolerance and morphine withdrawal-induced hyperalgesia. Lipoxins are endogenous lipoxygenase-derived eicosanoids that can function as "braking signals" in inflammation. The present study investigated the effect of 5 (S), 6 (R)-lipoxin A(4) methyl ester (LXA(4)ME), a stable synthetic analog of lipoxin A(4), on the expression of antinociceptive tolerance and withdrawal-induced hyperalgesia in chronic morphine-treated rats. Chronic morphine administration through repeated subcutaneous injection induced the development of hyperalgesia and the expression of spinal antinociceptive tolerance to morphine. However, LXA(4)ME treatment significantly attenuated the development of hyperalgesia and the expression of spinal antinociceptive tolerance to intrathecal morphine in both mechanical and thermal test. Moreover, the administration of LXA(4)ME during the induction of morphine tolerance inhibited the activation of microglia and astrocytes; reduced the expression of proinflammatory cytokines interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha); upregulated the expression of anti-inflammatory cytokines IL-10 and transforming growth factor-beta 1 (TGF-beta 1); and inhibited nuclear factor-kappa B (NF-kappa B) activation at the L5 lumbar spinal cord. These results suggest that treatment of LXA(4)ME provides a potential preventative or therapeutic approach for morphine tolerance and associated abnormal pain sensitivity. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.