Blockade of Erythropoietin-Producing Human Hepatocellular Carcinoma Receptor B1 in Spinal Dorsal Horn Alleviates Visceral Pain in Rats.

Xiu-Liang Li,Nong He,Jia-Xiang Ni,Cheng-Wen Li,Fu-Shan Xue,Chen-Li Sun,Yuan-Zhang Tang,Takahiro Ushida

doi:10.1155/2021/7582494

Xiu-Liang Li, Nong He + Show 6 more

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https://doi.org/10.1155/2021/7582494

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Abstract

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.

Highlights

Abdominal pain is one of the major and troublesome hallmarks of gastrointestinal diseases, such as gastrointestinal tumors, inflammatory bowel disease, and irritable bowel syndrome
Another study using ephrinB2 knockout animals demonstrated that both ephrinB2 and EphB1 played important roles in 2, 4, 6-trinitrobenzene sulfonic acid- (TNBS) induced chronic visceral pain, but only ephrinB2 was involved in the development of stress-induced visceral pain [33]
It remains unclear whether administration of specific blockers to interrupt the phosphorylation of EphB1 and/or expression of ephrinB2 would attenuate visceral pain. us, this experiment was designed to assess the spinal expressions of EphB1 and ephrinB2 and their phosphorylation levels in a rat model of visceral pain induced by intracolonic injection of TNBS and determine the effects of using an EphB1 receptor blocking reagent on the development of visceral pain and the spinal expression of EphB1 receptors

Summary

Introduction

Abdominal pain is one of the major and troublesome hallmarks of gastrointestinal diseases, such as gastrointestinal tumors, inflammatory bowel disease, and irritable bowel syndrome. Only a few studies are focused on the involvement of ephrinB2/EphB1 signaling pathway in the pathogenesis of visceral pain [32, 33]. Another study using ephrinB2 knockout animals demonstrated that both ephrinB2 and EphB1 played important roles in 2, 4, 6-trinitrobenzene sulfonic acid- (TNBS) induced chronic (postinflammatory) visceral pain, but only ephrinB2 was involved in the development of stress-induced visceral pain [33]. Most important, it remains unclear whether administration of specific blockers to interrupt the phosphorylation of EphB1 and/or expression of ephrinB2 would attenuate visceral pain. It remains unclear whether administration of specific blockers to interrupt the phosphorylation of EphB1 and/or expression of ephrinB2 would attenuate visceral pain. us, this experiment was designed to assess the spinal expressions of EphB1 and ephrinB2 and their phosphorylation levels in a rat model of visceral pain induced by intracolonic injection of TNBS and determine the effects of using an EphB1 receptor blocking reagent on the development of visceral pain and the spinal expression of EphB1 receptors

Data and Methods

Results

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