Activation of ephrinB-EphB receptor signalling in rat spinal cord contributes to maintenance of diabetic neuropathic pain
Activation of ephrinB-EphB receptor signalling in rat spinal cord contributes to maintenance of diabetic neuropathic pain
复制标题
大鼠脊髓中 ephrinB–EphB 受体信号的激活有助于维持糖尿病神经性疼痛
DOI：
10.1002/ejp.922
复制
发表时间：
2017-02-01
影响因子：
3.6
通讯作者：
Song, X-J
中科院分区：
文献类型：
--
作者：
Deng, X-T;Wu, M-Z;Song, X-J
背景糖尿病神经病理性疼痛（Diabetic neuropathic pain，DNP）是一种严重而难治的疼痛。DNP的具体细胞和分子机制仍然难以捉摸，其治疗受到限制。我们调查EphB 1受体在DNP的发展中的作用。MethodsDiabetic neuropathic pain在雄性，成年，Sprague-Dawley大鼠由一个单一的IP链脲佐菌素（STZ）或四氧嘧啶。Western blot分析和免疫组化分析脊髓中EphB 1受体的表达以及胶质细胞和促炎细胞因子的活化。DNP表现为机械性异常性疼痛，这是通过测量的发生率的后爪的机械压痕电冯弗雷filaments.ResultsDiabetic神经性疼痛和高血糖的反应，同时在约70%的动物，接受腹腔注射STZ或四氧嘧啶的脚撤回。EphB 1的磷酸化，星形胶质细胞和小胶质细胞的活化，以及肿瘤坏死因子（TNF）-和白细胞介素（IL）-1在脊髓中的水平显着增加与DNP大鼠。脊髓阻断EphB 1受体激活后，STZ注射后的后期显着抑制建立的机械异常性疼痛以及激活的星形胶质细胞和小胶质细胞和TNF-α和IL-1的活性。结论脊髓EphB 1受体的激活对糖尿病疼痛的维持起重要作用，但对糖尿病疼痛的诱导无影响。EphB 1受体可能是缓解糖尿病疼痛的潜在靶点。意义脊髓EphB 1受体的激活对维持糖尿病神经病理性疼痛是至关重要的，但对糖尿病疼痛的诱导并不重要。脊髓阻断EphB 1受体激活抑制持续的糖尿病神经病理性疼痛。
BackgroundDiabetic neuropathic pain (DNP) is severe and intractable in clinic. The specific cellular and molecular mechanisms underlying DNP remain elusive and its treatment are limited. We investigated roles of EphB1 receptor in the development of DNP.MethodsDiabetic neuropathic pain was produced in male, adult, Sprague-Dawley rats by a single i.p. streptozotocin (STZ) or alloxan. Western blot analysis and immunohistochemistry were used to analyse expression of EphB1 receptor as well as the activation of the glial cells and the pro-inflammatory cytokines in the spinal cord. DNP manifested as mechanical allodynia, which was determined by measuring incidence of foot withdrawal in response to mechanical indentation of the hind paw by an electro von Frey filament.ResultsDiabetic neuropathic pain and high blood glucose were exhibited simultaneously in around 70% of animals that received i.p. STZ or alloxan. Phosphorylation of EphB1, activation of the astrocytes and microglial cells, and level of tumour necrosis factor (TNF)- and interleukin (IL)-1 in the spinal cord were significantly increased in rats with DNP. Spinal blocking EphB1 receptor activation in the late phase after STZ injection significantly suppressed the established mechanical allodynia as well as activation of the astrocytes and microglial cells and activity of TNF- and IL-1. However, spinal treatment of EphB1-Fc in the early phase after STZ injection did not prevent the induction of DNP.ConclusionsEphB1 receptor activation in the spinal cord is critical to the maintenance, but not induction of diabetic pain. EphB1 receptor may be a potential target for relieving the established diabetic pain.SignificanceActivation of EphB1 receptor in the spinal cord is critical to maintaining the established diabetic neuropathic pain, but not to diabetic pain induction. Spinal blocking EphB1 receptor activation suppresses ongoing diabetic neuropathic pain.