脊髓水平GABAA受体在异丙酚对内脏痛大鼠镇痛效应中的作用

Involvement of spinal cord GABAA receptor in the analgesic effect of propofol on visceral pain

目的 探讨脊髓水平γ-氨基丁酸（GABA）A受体在异丙酚对内脏痛大鼠镇痛效应中的作用。方法 35只雄性SD大鼠，体重180—240g，随机分为5组，每组7只，腹腔注射生理盐水0．5ml组（C组），腹腔注射异丙酚10mg／kg组（P1组），腹腔注射异丙酚20mg/kg组（P2组），鞘内注射荷包牡丹碱0．25馏组（B组），鞘内注射荷包牡丹碱0．25μg＋腹腔注射异丙酚10mg/kg组（BP组）。采用结直肠扩张法制备内脏痛动物模型，以腹壁明显收缩变平的最小扩张压力值为痛阈，观察给药前即刻（T0）及给药后5min（T1）、10min（T2）、15min（T3）、20min（T4）、25min（T5）、30min（k）、40min（B）、50min（T8）大鼠的痛阈，并计算最大镇痛效应百分率（MPE）。结果 与C组比较，P1组T1-4时、P2组T1-5，时的痛阈升高（P〈0．05或0．01）；与P1组比较，P2组痛阈升高（P〈0．01）。与P1组比较，B组T1-4时MPE降低，BP组T2-4时MPE升高（P〈0．05或0．01）；与B组比较，BP组，T1-4时MPE升高（P〈0．05或0．01）。结论 异丙酚部分通过介导脊髓水平GABAA受体，对大鼠结直肠扩张所致内脏痛具有镇痛作用。

Objective To determine if spinal cord GABAA receptor is involved in the analgesic effect of propofol on visceral pain. Methods Thirty-five male SD rats weighing 180-240 g were used in this study. Intrathecal （IT） catheter was placed at L3-4 interspace. Visceral pain was produced by colorectal distension with a 7 cm long balloon inserted into the rectum and descending colon under anesthesia. The animals were randomly divided into 5 groups （ n = 7 each） ： group Ⅰ received intrapefitoneal （IP） normal saline 0.5 ml （C） ; group Ⅱ and m received propofol 10 and 20 mg/kg IP respectively （P1, P2） ; group Ⅳ received bicuculline （Bic） 0.25 μg IT （B） and groupV received Bic 0.25 μg IT ＋ propofol 10 mg/kg IP （BP）. Propofol IP was given 10 min after IT bicuculline. Visceral pain threshold was measured by the minimal pressure that flattens the abdomen during colorectal distension. The analgesic effect was assessed by the change in the visceral pain threshold before and after drug administration. Results The visceral pain threshold was significantly increased at 5 min after propofol IP in group P1 and P2 . The analgesic effect reached the peak at 10-15 min and lasted 20-25 min （ P 〈 0.05 or 0.01 ）. The analgesia was stronger and lasted longer in group P2 than in group P1 . IT Bic had no significant effect on visceral pain threshold in group B （ Ⅳ ）. The visceral pain threshold was significantly increased after IP propofol 10 mg/kg in group BP （ V ） but the analgesia was significantly weaker in group BP than in group P1. Conclusion Intrathecal propofol has antinociceptive effect on colorectal distension-induced visceral pain in rats through GABAA receptor action to some extent.