Objective. This experiment was designed to determine whether erythropoietin-producing human hepatocellular carcinoma (Eph) receptors were involved in the development of visceral pain. Methods. Adult male Sprague-Dawley rats were randomly divided into three groups receiving different treatments (n = 16 per group): intracolonic vehicle (control group), intracolonic 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) (TNBS group), and intracolonic TNBS and intrathecal EphB1 receptor blocking reagent (TNBS + EphB2-Fc group). Visceral hyperalgesia was evaluated with quantification of visceral pain threshold induced by colorectal distention. The spinal expressions of EphB1 and ephrinB2 and levels of their phosphorylated forms (p-EphB1 and p-ephrinB2) were assessed by Western blotting and immunohistochemistry. Results. The TNBS-treated rats developed significant visceral hyperalgesia. The spinal expressions of EphB1, p-EphB1, ephrinB2, and p-ephrinB2 were significantly increased in the TNBS group compared with the control group, but visceral hyperalgesia and elevation of spinal EphB1 and p-EphB1 expressions were evidently alleviated by intrathecal administration of EphB2-Fc in the TNBS + EphB2-Fc group. The number of EphB1- and p-EphB1-immunopositive cells, the average optical (AO) value of EphB1, and its phosphorylated form in the spinal dorsal horn were significantly increased in the TNBS group than in the control group, but they were obviously reduced by intrathecal administration of EphB2-Fc. There were no significant differences in the number of ephrinB2- and p-ephrinB2-immunopositive cells and the AO value of ephrinB2 and its phosphorylated form between the TNBS and TNBS + EphB2-Fc groups. Conclusion. EphB1 receptors in the spinal dorsal horn play a pivotal role in the development of visceral pain and may be considered as a potential target for the treatment of visceral pain.

中文翻译：

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脊髓背角中促红细胞生成素产生人肝细胞癌受体B1的阻滞减轻大鼠的内脏痛。

目标。本实验旨在确定产生促红细胞生成素的人肝细胞癌（Eph）受体是否参与内脏痛的发展。方法。将成年雄性Sprague-Dawley大鼠随机分为三组，分别接受不同的治疗（n 每组= 16）：结肠内媒介物（对照组），结肠内2、4、6-三硝基苯磺酸（TNBS）（TNBS组）以及结肠内TNBS和鞘内EphB1受体阻断剂（TNBS + EphB2-Fc组）。通过量化由结肠直肠扩张引起的内脏疼痛阈值来评估内脏痛觉过敏。通过蛋白质印迹和免疫组织化学评估EphB1和ephrinB2的脊髓表达及其磷酸化形式（p-EphB1和p-ephrinB2）的水平。结果。TNBS处理的大鼠发展出明显的内脏痛觉过敏。与对照组相比，TNBS组中EphB1，p-EphB1，ephrinB2和p-ephrinB2的脊髓表达明显增加，但鞘内注射EphB2明显减轻了内脏痛觉过敏和脊髓EphB1和p-EphB1表达的升高TNBS + EphB2-Fc组中的-Fc。TNBS组的脊髓背角中EphB1和p-EphB1免疫阳性细胞的数量，EphB1的平均光学（AO）值及其磷酸化形式比对照组明显增加，但明显减少通过鞘内施用EphB2-Fc。结论。脊髓背角中的EphB1受体在内脏痛的发展中起着关键作用，可以被认为是治疗内脏痛的潜在靶标。