急性结肠炎性内脏痛中MAPK通路蛋白的表达及吗啡治疗效果

MAPK PATHWAY PROTEIN EXPRESSION IN ACUTE COLITIS VISCERAL PAIN MODEL AND ANALGESIC EFFECT OF MORPHINE

目的：探讨MAPK通路在急性结肠炎性内脏痛中的作用.方法：实验一,将大鼠分为正常对照组,结肠炎组（结肠内注射6％醋酸0.5 ml）和制模对照组（结肠内注入等量生理盐水）.观察大鼠疼痛行为和结肠炎症反应;用Western blot法检测脊髓内MAPK通路蛋白表达.实验二,将大鼠分为吗啡预治疗组（制模前皮下注射吗啡5 mg/kg）和溶剂（生理盐水）对照组,所有大鼠同前制模,观察终点同实验一.结果：急性结肠炎可引起L5～S1脊髓内pERK、pJNK显著升高,在C2～4脊髓内无明显变化;p38蛋白无明显变化;吗啡预治疗可明显减轻内脏疼痛程度,降低结肠炎症分级,降低L5～S1脊髓内pERK和pJNK的表达,升高C2～4脊髓内pERK的表达.结论：MAPK通路通过ERK和JNK的激活介导急性结肠炎性疼痛,吗啡治疗作用也与这两个通路有关.

Objective：Visceral pain is one of the most common forms of pain produced by disease,and one of the most frequent reasons why patients seek medical attention.This study investigates the role of the mitogen-activated protein kinase （MAPK） pathway in the development of acute colitis-induced visceral pain in order to find new targets for treating visceral pain.Methods：Part 1.Adult male Sprague Dawley （SD） rats were divided into a na（i）ve control group,a colitis group （0.5 mL 6 ％ acetic acid,intra-colonic）,and a sham-operated control group （0.5 mL normal saline,intra-colonic）.Spontaneous abdominal painrelated behaviors were recorded.The severity of colitis was evaluated by histological changes and the protein expression of Phospho-extracellular signaling-regulated kinase （pERK）,c-Jun N-terminal kinase （pJNK）,and p38 in the spinal cord were analyzed by Western blotting.Part 2.Adult male Sprague Dawley （SD） rats were divided into a morphine-pretreated colitis group （5 mg kg-1 morphine subcutaneously 30 min prior to intra-colonic acetic acid） and a vehicle（saline）-pretreated colitis group.All the rats in part 2 underwent intracolonic acetic acid administration.The study endpoints of part 2 were the same as those of part 1.Results：In comparison with the sham-operated control group,pERK and pJNK expression in the spinal cord of the colitis group was found to increase significantly in the lumbar spinal cord （L5-S1） but not in the cervical spinal cord （C2～4）.The expression of p38 did not change significantly.Pretreatment with morphine reduced pain-related behavior,increased spontaneous behavior,decreased pERK and pJNK expression in the lumbar spinal cord （L5-S1）,and increased pERK expression in the cervical spinal cord （C2～4）.The histological grades of the morphine-pretreated colitis group were significantly lower than those of the vehicle-pretreated colitis group.Conclusion：This study suggests that the MAPK pathway may mediate acute colitis visceral pain by activating ERK and JNK.The analgesic and anti-inflammatory effects of morphine may be mediated via ERK and JNK pathways.ERK and JNK may be considered as new targets for visceral pain treatment.