Hasanein Parisa, Parviz Mohsen
Department of Biology, School of Basic Sciences, Bu-Ali Sina University, Hamedan, Iran.
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Electrophysiological Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Pharmacol Biochem Behav. 2014 Sep;124:226-30. doi: 10.1016/j.pbb.2014.06.014. Epub 2014 Jun 20.
Increased activity of the endogenous opioid system in cholestasis results in analgesia. GABAA receptors have been ascribed both pronociceptive and antinociceptive roles in pain modulation. Considering the elevated endogenous opioid tone in cholestasis and the existence of close interaction between the GABAergic and opioidergic systems in pain control, the involvement of GABAA receptors in modulation of nociception in a model of elevated endogenous opioid tone, cholestasis, was investigated using muscimol and bicuculline as selective GABAA receptor agonist and antagonist respectively. Cholestasis was induced by ligation of the main bile duct using two ligatures and transsection of the duct between them. Cholestatic rats had increased tail-flick latencies (TFLs) compared to non-cholestatic rats. Administration of muscimol (0.2 and 0.4 mg/kg, s.c.) and bicuculline (0.5 and 1mg/kg, s.c.) to the cholestatic groups significantly increased and decreased respectively TFLs compared to the saline treated cholestatic group. Muscimol antinociception in cholestatic animals was attenuated by co-administration of naloxone or bicuculline. Furthermore, the combination of bicuculline and naloxone completely reversed the increased TFLs of cholestatic rats back to the level of unoperated animals. Muscimol and bicuculline injections into non-cholestatic animals did not alter TFLs. At the doses used here, none of the drugs impaired motor coordination, as revealed by the rotarod test. This study shows the involvement of GABAA receptors in pain modulation during cholestasis in rats.
胆汁淤积时内源性阿片系统活性增强会导致镇痛作用。GABAA受体在疼痛调节中既具有促痛作用，也具有抗痛作用。鉴于胆汁淤积时内源性阿片张力升高，以及在疼痛控制中GABA能系统与阿片能系统之间存在密切相互作用，本研究分别使用蝇蕈醇和荷包牡丹碱作为选择性GABAA受体激动剂和拮抗剂，探讨了GABAA受体在胆汁淤积（一种内源性阿片张力升高的模型）中对伤害感受调制的影响。通过使用两道结扎线结扎胆总管并在两道结扎线之间横断胆管来诱导胆汁淤积。与非胆汁淤积大鼠相比，胆汁淤积大鼠的甩尾潜伏期（TFL）延长。与生理盐水处理的胆汁淤积组相比，向胆汁淤积组注射蝇蕈醇（0.2和0.4mg/kg，皮下注射）和荷包牡丹碱（0.5和1mg/kg，皮下注射）分别显著延长和缩短了TFL。在胆汁淤积动物中，纳洛酮或荷包牡丹碱的共同给药减弱了蝇蕈醇的抗痛作用。此外，荷包牡丹碱和纳洛酮的联合使用完全将胆汁淤积大鼠延长的TFL恢复到未手术动物的水平。向非胆汁淤积动物注射蝇蕈醇和荷包牡丹碱未改变TFL。如转棒试验所示，在此使用的剂量下，没有一种药物损害运动协调性。本研究表明GABAA受体参与了大鼠胆汁淤积期间的疼痛调制。
