INVOLVEMENT OF THE SPINAL NALP1 INFLAMMASOME IN NEUROPATHIC PAIN AND ASPIRIN-TRIGGERED-15-EPI-LIPDXIN A4 INDUCED ANALGESIA
INVOLVEMENT OF THE SPINAL NALP1 INFLAMMASOME IN NEUROPATHIC PAIN AND ASPIRIN-TRIGGERED-15-EPI-LIPDXIN A4 INDUCED ANALGESIA
复制标题
脊髓 nalp1 炎性体参与神经性疼痛和阿司匹林触发的 15-epi-lipdxin a4 诱导镇痛
DOI：
10.1016/j.neuroscience.2013.09.028
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发表时间：
2013-12-19
期刊：
影响因子：
3.3
通讯作者：
Wang, Y. -Q.
中科院分区：
文献类型：
--
作者：
Li, Q.;Tian, Y.;Wang, Y. -Q.
神经炎症在神经损伤引起的神经病理性疼痛中起重要作用，但神经炎症在神经病理性疼痛中的分子机制尚不清楚。白细胞介素-113（IL-113）作为一种重要的炎症细胞因子，广泛参与神经病理性疼痛的病理过程。炎症小体caspase-1平台是IL-1D成熟的主要机制之一。脂氧素是一种内源性抗炎脂质，已被证明可有效缓解神经病理性疼痛行为。本研究旨在检查炎性体caspase-1 IL-ID平台是否参与慢性压迫性损伤（CCI）诱导的神经病理性疼痛和脂氧素诱导的镇痛。CCI手术后，大鼠同侧脊髓中成熟IL-ID显著增加，并且由NALP 1组成的炎性小体平台（NAcht富含亮氨酸重复序列蛋白1）、半胱天冬酶-1和ASC脊髓星形胶质细胞和神经元中也有凋亡相关的斑点样蛋白（含有半胱天冬酶激活的募集结构域）被激活，尤其是在脊髓背角的浅层;阿司匹林触发的-15 epi-lipoxin A4（ATL），共享内源性脂氧素的有效作用，被给予CCI大鼠。反复鞘内注射ATL可显著减弱CCI诱导的热痛敏，并显著抑制NALP 1炎性小体激活、caspase-1裂解和IL-10成熟。这些结果表明，脊髓NALP 1炎性体参与了CCI诱导的神经病理性疼痛，ATL的镇痛作用与抑制NALP 1炎性体激活有关。(C)2013年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Neuroinflammation plays an important role in nerve-injury-induced neuropathic pain, but the explicit molecular mechanisms of neuroinflammation in neuropathic pain remain unclear. As one of the most critical inflammatory cytokines, interleukin-113 (IL-ID) has been regarded as broadly involved in the pathology of neuropathic pain. The inflammasome caspase-1 platform is one primary mechanism responsible for the maturation of IL-ID. Lipoxins, a type of endogenous anti-inflammatory lipid, have proved to be effective in relieving neuropathic pain behaviors. The present study was designed to examine whether the inflammasome caspase-1 IL-ID platform is involved in chronic constriction injury (CCI)-induced neuropathic pain and in lipoxin-induced analgesia. After rats were subjected to the CCI surgery, mature IL-ID was significantly increased in the ipsilateral spinal cord, and the inflammasome platform consisting of NALP1 (NAcht leucine-rich-repeat protein 1), caspase-1 and ASC (apoptosis-associated speck-like protein containing a caspase-activating recruitment domain) was also activated in spinal astrocytes and neurons, especially at the superficial laminae of the spinal dorsal horn; The aspirin-triggered-15epi-lipoxin A4 (ATL), which shares the potent actions of the endogenous lipoxins, was administered to the CCI rats. Repeated intrathecal injection with ATL markedly attenuated the CCI-induced thermal hyperalgesia and significantly inhibited NALP1 inflammasome activation, caspase-1 cleavage, and IL-10 maturation. These results suggested that spinal NALP1 inflammasome was involved in the CCI-induced neuropathic pain and that the analgesic effect of ATL was associated with suppressing NALP1 inflammasome activation. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.