Sciatic endometriosis induces mechanical hypersensitivity, segmental nerve damage, and robust local inflammation in rats.
Sciatic endometriosis induces mechanical hypersensitivity, segmental nerve damage, and robust local inflammation in rats.
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坐骨神经内膜异位症引起大鼠机械过敏、节段神经损伤和强烈的局部炎症
DOI：
10.1002/ejp.827
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发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Zhang JM
中科院分区：
文献类型：
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作者：
Chen S;Xie W;Strong JA;Jiang J;Zhang JM
子宫内膜异位症是一种常见的疼痛原因，包括根性疼痛。异位子宫内膜组织可能直接影响周围神经，包括坐骨神经，这还没有在动物中建模。我们通过将自体子宫组织移植到坐骨神经周围，建立了大鼠坐骨神经子宫内膜异位症模型。对照组动物接受了类似的手术，但接受了盆腔脂肪组织移植。子宫移植物存活，并发展成充满液体的囊肿;邻近的神经显示肿胀和损伤的迹象。术后前两周，同侧后爪的机械和冷超敏反应和异常性疼痛逐渐发展，在2 - 5周达到峰值，并在7周时几乎消退。对照组动物在这些疼痛行为中仅表现出微小的变化。在3周时观察到子宫移植物和邻近神经中的炎症组织学体征，但在7周时消退。在体内纤维记录显示增加的自发活动，尤其是C纤维，在坐骨神经近端的子宫移植。与正常神经或神经加脂肪移植物的样品相比，子宫移植物加坐骨神经样品中的几种促炎细胞因子，包括白细胞介素-18、VEGF、fractalkine和MIP-1α升高。生长相关蛋白43（GAP 43），再生神经纤维的标记物，观察到在邻近的坐骨神经以及在子宫移植。该模型与其他大鼠子宫内膜异位症模型有许多共同的特征，但也有一些独特的特征与神经病理性疼痛模型更密切相关。
Endometriosis is a common cause of pain including radicular pain. Ectopic endometrial tissue may directly affect peripheral nerves including the sciatic, which has not been modelled in animals. We developed a rat model for sciatic endometriosis by grafting a piece of autologous uterine tissue around the sciatic nerve. Control animals underwent a similar surgery but received a graft of pelvic fat tissue. The uterine grafts survived and developed fluid filled cysts; the adjacent nerve showed signs of swelling and damage. Mechanical and cold hypersensitivity and allodynia of the ipsilateral hindpaw developed gradually over the first two weeks after the surgery, peaked at 2 to 5 weeks, and was almost resolved by 7 weeks. Control animals showed only minor changes in these pain behaviors. Histological signs of inflammation in the uterine graft and in the adjacent nerve were observed at 3 weeks but were resolving by 7 weeks. In vivo fiber recording showed increased spontaneous activity, especially of C fibers, in sciatic nerve proximal to the uterine graft. Several pro-inflammatory cytokines including interluekin-18, VEGF, fractalkine, and MIP-1α, were elevated in the uterine graft plus sciatic nerve samples, compared to samples from normal nerve or nerve plus fat graft. Growth associated protein 43 (GAP43), a marker of regenerating nerve fibers, was observed in the adjacent sciatic nerve as well as in the uterine graft. This model shared many features with other rat models of endometriosis, but also had some unique features more closely related to neuropathic pain models.