Proteinase-Activated Receptor 2 Mediates Thermal Hyperalgesia and Is Upregulated in a Rat Model of Chronic Pancreatitis
Proteinase-Activated Receptor 2 Mediates Thermal Hyperalgesia and Is Upregulated in a Rat Model of Chronic Pancreatitis
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DOI：
10.1097/mpa.0b013e318201cbc1
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发表时间：
2011-03
期刊：
影响因子：
2.9
通讯作者：
Wei Zhang;Jun Gao;T. Zhao;Lei Wei;Wenbin Wu;Yu Bai;D. Zou;Zhaoshen Li
中科院分区：
文献类型：
--
作者：
Wei Zhang;Jun Gao;T. Zhao;Lei Wei;Wenbin Wu;Yu Bai;D. Zou;Zhaoshen Li
目的：慢性胰腺炎（CP）疼痛的机制尚未完全阐明。蛋白酶激活受体2（PAR2）在内脏痛中起着原伤害感受的作用。该研究旨在评估PAR2在背根神经节（DRGs）中的表达，并验证其在CP中热痛敏的作用。方法：采用三硝基苯磺酸胰管灌注法复制大鼠慢性胰腺炎模型。腹部痛觉过敏通过热撤退法测量。免疫荧光和Western blot检测PAR 2和瞬时受体电位香草酸1（TRPV 1）的表达。通过实时聚合酶链反应定量编码PAR 2的信使RNA。观察短期和长期乌司他丁治疗对CP大鼠腹部热痛敏的影响。结果：CP大鼠热退缩潜伏期缩短。蛋白酶激活受体2和TRPV1在DRG中显著上调。PAR 2蛋白表达的增加与热戒断症状和TRPV 1表达密切相关。短期乌司他丁治疗以剂量依赖性方式抑制CP大鼠热痛觉过敏的发展。结论：CP热痛敏与背根节PAR 2表达上调有关。蛋白酶激活受体2参与CP大鼠疼痛的产生。
Objectives: The mechanism of pain in chronic pancreatitis (CP) has yet to be explored. Proteinase-activated receptor 2 (PAR2) plays a pronociceptive role in visceral pain. The study aimed to assess the expression of PAR2 in dorsal root ganglia (DRGs) and validate its role of thermal hyperalgesia in CP. Methods: Chronic pancreatitis model was induced by trinitrobenzene sulfonic acid infusion into rat pancreatic ducts. Abdominal hyperalgesia was measured by thermal withdrawal latencies. The expression of PAR2 and transient receptor potential vanilloid 1 (TRPV1) were analyzed by immunofluorescence and Western blot. The messenger RNA encoding PAR2 was quantitated by real-time polymerase chain reaction. The effects of short-term and long-term ulinastatin treatment on abdominal thermal hyperalgesia of rats with CP were measured. Results: Rats with CP showed a decreased thermal withdrawal latency. Proteinase-activated receptor 2 and TRPV1 were significantly upregulated in DRGs. The increased PAR2 protein expression was tightly correlated with thermal withdrawal latencies and TRPV1 expression. Short-term ulinastatin treatment inhibited the development of thermal hyperalgesia of rats with CP in a dose-dependent manner. Conclusions: The thermal hyperalgesia in CP is associated with an up-regulation of the PAR2 in DRGs. Proteinase-activated receptor 2 was involved in the pain generation in rats with CP.