辣椒素受体拮抗剂治疗避水应激引起内脏痛觉过敏作用

Effects of Vanilloid Receptor Antagopnists on Visceral Hypersensitivity Induced by Water Avoid Stress

目的研究避水应激引起内脏痛觉敏感性的变化及特异性辣椒素受体(VR1)拮抗剂辣椒平与非特异性VR1拮抗剂钌红对避水应激引起内脏痛觉过敏的治疗作用。方法将6周龄雄性Wistar大鼠54只分为无应激对照组(Neg组,n=18)、生理盐水对照组(NS组,n=12)、辣椒平治疗组(CZP组,n=12)、钌红治疗组(RR组,n=12),Neg组又分为三个小组,分别为直肠内注入生理盐水组、直肠内注入辣椒素组、直肠扩张组,NS组、CZP组和RR组只分为直肠内注入辣椒素组和直肠扩张组两小组,每小组均为6只动物。给予避水应激,每天1h连续10d。第11天Neg组与NS组腹腔注射溶媒,CZP组腹腔注射辣椒平,RR组腹腔注射钌红,30min后每小组6只动物直肠内注入生理盐水或辣椒素,进行疼痛评分,或给予结直肠扩张(CRD)刺激,进行腹直肌肌电记录。结果避水应激引起动物对直肠注射辣椒素敏感性增加,腹腔注射辣椒平与钌红均能抑制注射辣椒素引起的疼痛反应;避水应激也引起动物CRD刺激后腹直肌肌电活动增加,腹腔注射辣椒平与钌红均能降低肌电活动的增加幅度,而钌红则完全抑制肌电活动的增加。结论辣椒素受体拮抗剂可抑制避水应激引起的内脏痛觉过敏,辣椒素受体参与内脏痛觉过敏的发生过程。

Objective To evaluate the visceral sensitivity after water-avoid stress and the effects of capsazepine and ruthenium red on visceral hypersensitivity induced by water-avoid stress. Methods 54 Wistar rats were divided into non-stress group （group Neg, n=18）, normal saline group （group NS, n=12）, capsazepine group （group CZP, n=12） and ruthenium red group （group RR, n=12）. There were three subgroups of rates in the group Neg （intracolonic injection of NS, capsaicin and eolorectal distention）, and two subgroups in other three groups （intracolonic injection of eapsaicin and eolorectal distention ）. Each subgroup consisted of 6 rats. All rats were given with water avoid-stress 1 h a day for 10 days. At day-11, rats in the group Neg and group NS were then injected with solvent and rats in the group CZP and group RR were injected with capsazepine and ruthenium red, respectively. Pain induced by intracolonic injection with normal saline or capsaicin were scored in each group at 30 min after intraperitoneally injection. Abdominal rectus abdomiuis electromyogram （EMG） were monitored after colorectal distention （CRD） in another 6 rats in each group at 30 rain after intraperitoneally injection. Results Water-avoid stress could increase the sensitivity to intracolonic injection of capsaicin. Intraperitoneal injection with capsazepine and ruthenium red could inhibit the pain behaviors induced by capsaicin. EMG counts were also increased after stress, capsazepine partially inhibited the increase in EMG counts, and ruthenium red completely inhibited the increase. Conclusion Antagonists of vanilloid receptor are effective to attenuate visceral hyperalgesia induced by water-avoid stress, and vanilloid receptor mediates process of visceral hyperalgesia.