Resolvin D1 Inhibits Mechanical Hypersensitivity in Sciatica by Modulating the Expression of Nuclear Factor-κB, Phospho-extracellular Signal-regulated Kinase, and Pro- and Antiinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion
Resolvin D1 Inhibits Mechanical Hypersensitivity in Sciatica by Modulating the Expression of Nuclear Factor-κB, Phospho-extracellular Signal-regulated Kinase, and Pro- and Antiinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion
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DOI：
10.1097/aln.0000000000001010
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发表时间：
2016-04-01
期刊：
影响因子：
8.8
通讯作者：
Sun, Tao
中科院分区：
文献类型：
--
作者：
Liu, Zhi-hua;Miao, Gui-shen;Sun, Tao
背景资料：越来越多的证据表明，脊髓炎症和免疫反应在椎间盘突出引起的神经根性疼痛的过程中起着重要的作用。Resolvin D1（RvD 1）已被证明具有有效的镇痛和抗伤害作用。方法：建立大鼠非压迫性腰椎间盘突出症模型，采用von Frey试验评价RvD 1的镇痛作用，观察21 d（n = 8/组）。鞘内注射溶剂或RvD 1（10或100 ng），连续3天术后。在第7天，切除同侧脊髓背角和L5背根神经节（DRG），以评估肿瘤坏死因子-（TNF-）、白细胞介素-1（IL-1）、IL-10和转化生长因子-1（TGF-1）的表达以及核因子-B（NF-B）/p65和磷酸化细胞外信号调节激酶（p-ERK）信号的激活结果：髓核植入L5背根节可引起长时间的机械性痛觉超敏反应，抑制脊髓背角和背根节中IL-10和TGF-1的产生，上调TNF-α、IL-1、NF-B/p65和p-ERK的表达。鞘内注射RvD 1可抑制TNF-α和IL-1的表达，增加IL-10和TGF-1的释放，抑制NF-B/p65和p-ERK的表达，并呈剂量依赖性。结论：RvD 1可能通过调节炎症介质和NF-B/p65和p-ERK通路减轻神经病理性疼痛。其抑制和促消退特性可能为神经病理性疼痛的管理提供新的治疗方法。
Background: Accumulating evidence indicates that spinal inflammatory and immune responses play an important role in the process of radicular pain caused by intervertebral disk herniation. Resolvin D1 (RvD1) has been shown to have potent antiinflammatory and antinociceptive effects. The current study was undertaken to investigate the analgesic effect of RvD1 and its underlying mechanism in rat models of noncompressive lumbar disk herniation.Methods: Rat models of noncompressive lumber disk herniation were established, and mechanical thresholds were evaluated using the von Frey test during an observation period of 21 days (n = 8/group). Intrathecal injection of vehicle or RvD1 (10 or 100 ng) was performed for three successive postoperative days. On day 7, the ipsilateral spinal dorsal horns and L5 dorsal root ganglions (DRGs) were removed to assess the expressions of tumor necrosis factor- (TNF-), interleukin-1 (IL-1), IL-10, and transforming growth factor-1 (TGF-1) and the activation of nuclear factor-B (NF-B)/p65 and phospho-extracellular signal-regulated kinase (p-ERK) signaling (n = 30/group).Results: The application of nucleus pulposus to L5 DRG induced prolonged mechanical allodynia, inhibited the production of IL-10 and TGF-1, and up-regulated the expression of TNF-, IL-1, NF-B/p65, and p-ERK in the spinal dorsal horns and DRGs. Intrathecal injection of RvD1 showed a potent analgesic effect, inhibited the up-regulation of TNF- and IL-1, increased the release of IL-10 and TGF-1, and attenuated the expression of NF-B/p65 and p-ERK in a dose-dependent manner.Conclusions: The current study showed that RvD1 might alleviate neuropathic pain via regulating inflammatory mediators and NF-B/p65 and p-ERK pathways. Its antiinflammatory and proresolution properties may offer novel therapeutic approaches for the management of neuropathic pain.