LIPOXIN A4 ATTENUATES RADICULAR PAIN POSSIBLY BY INHIBITING SPINAL ERK, JNK AND NF-κB/P65 AND CYTOKINE SIGNALS, BUT NOT P38, IN A RAT MODEL OF NON-COMPRESSIVE LUMBAR DISC HERNIATION
LIPOXIN A4 ATTENUATES RADICULAR PAIN POSSIBLY BY INHIBITING SPINAL ERK, JNK AND NF-κB/P65 AND CYTOKINE SIGNALS, BUT NOT P38, IN A RAT MODEL OF NON-COMPRESSIVE LUMBAR DISC HERNIATION
复制标题
在非压迫性腰椎间盘突出症大鼠模型中，脂氧素 A4 可能通过抑制脊髓 ERK、JNK 和 NF-κB/p65 和细胞因子信号（但不是 p38）来减轻神经根痛
DOI：
10.1016/j.neuroscience.2015.04.060
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发表时间：
2015-08-06
期刊：
影响因子：
3.3
通讯作者：
Sun, T.
中科院分区：
文献类型：
--
作者：
Miao, G. -S;Liu, Z. -H;Sun, T.
髓突核（NP）引起的炎症反应在神经根痛过程中起着至关重要的作用。脂毒素是一类独特的脂质介质，具有抗炎和促炎作用。本研究旨在探讨鞘内脂素A(4) （LXA(4)）是否能减轻NP应用于L5背根神经节（DRG）大鼠模型的机械异常性痛。建立NP作用于L5 DRG的非压缩模型，并在大鼠鞘内置管给药。术后连续3天，每天鞘内注射载药剂或LXA(4) （10 ng或100 ng）。测定机械阈值，切除同侧腰椎（L4-L6）背角段，测定肿瘤坏死因子- α (tnf - α)、IL-1 β、转化生长因子- β 1 （tgf - β 1）、IL-10表达及NF-kappa B/p65、细胞外信号调节激酶（ERK）、C-Jun n -末端激酶（JNK）、P38表达。NP应用于DRG诱导大鼠机械异常性痛，增加了同侧腰椎背角（L4-L6）节段的促炎因子（tnf - α和IL-1 β）、NF-kappa B/p65、磷酸化erk （p-ERK）、-JNK （p-JNK）和-P38 （p-p38）的表达，降低了抗炎因子（tgf - β 1和IL-10）的表达。鞘内注射LXA(4)可减轻神经性疼痛的发展，抑制促炎细胞因子（tnf - α和IL-1 β）的上调，上调抗炎细胞因子（tgf - β 1和IL-10）的表达，减弱NF-kappa B/p65、p-ERK、p-JNK的活化，但不减弱p-p38的活化，且呈剂量依赖性。在这项研究中，我们证明了LXA(4)能有效缓解非压缩性腰椎间盘突出大鼠模型的神经根痛。LXA的抗炎和促溶解特性(4)在治疗椎间盘突出引起的神经根性疼痛方面显示出很大的希望。(c) 2015年。Elsevier Ltd.出版。版权所有。
Inflammatory response induced by protrused nucleus pulposus (NP) has been shown to play a crucial role in the process of radicular pain. Lipoxins represent a unique class of lipid mediators that have anti-inflammatory and proresolving action. The present study was undertaken to investigate if intrathecal lipoxin A(4) (LXA(4)) could alleviate mechanical allodynia in the rat models of application of NP to the L5 dorsal root ganglion (DRG). Non-compressive models of application of NP to L5 DRG were established and intrathecal catheterization for drug administration was performed in rats. Daily intrathecal injection of vehicle or LXA(4) (10 ng or 100 ng) was performed for three successive days post-operation. Mechanical thresholds were tested and the ipsilateral lumbar (L4-L6) segment of spinal dorsal horns were removed for the determination of tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, transforming growth factor-beta 1 (TGF-beta 1) and IL-10 expression and NF-kappa B/p65, extracellular signal-regulated kinase (ERK), C-Jun N-terminal kinase (JNK) and P38 expression. Application of NP to DRG in rats induced mechanical allodynia, increased the expression of pro-inflammatory factors (TNF-alpha and IL-1 beta), NF-kappa B/p65, the phosphorylated-ERK (p-ERK), -JNK (p-JNK) and -P38 (p-p38) and decreased the expression of anti-inflammatory cytokines (TGF-beta 1 and IL-10) in the ipsilateral lumbar (L4-L6) segment of spinal dorsal horns. Intrathecal injection of LXA(4) alleviated the development of neuropathic pain, inhibited the upregulation of pro-inflammatory cytokines (TNF-alpha and IL-1 beta), upregulated the expression of anti-inflammatory cytokines (TGF-beta 1 and IL-10) and attenuated the activation of NF-kappa B/p65, p-ERK, p-JNK, but not p-p38, in a dose-dependent manner. In this study, we have demonstrated that LXA(4) potently alleviate radicular pain in a rat model of non-compressive lumbar disc herniation. The anti-inflammatory and pro-resolution properties of LXA(4) have shown a great promise for the management of radicular pain caused by intervertebral disc herniation. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.