H + H, Metropolitan, PAGNY, NY, United States; New York Medical College, Valhalla, NY, United States.
Med Hypotheses. 2018 Jan;110:86-89. doi: 10.1016/j.mehy.2017.11.002. Epub 2017 Nov 6.
The pruritus of cholestasis is a maddening complication of liver disease. Increased opioidergic tone contributes to the pruritus of cholestasis, as evidenced by the amelioration of the symptom by opiate antagonists. Obeticholic acid, an agonist of the farnesoid receptor, has been approved for the treatment of primary biliary cholangitis, a disease characterized by cholestasis; this drug is associated with pruritus, the cause of which is unknown. In animal models, bile acids, which accumulate in the body as a result of cholestasis, have been reported to cause scratching behavior mediated by the TGR5 receptor, in an opioid-dependent manner, in laboratory animals. As obeticholic acid also binds to TGR5, the pruritus caused by this drug is likely to be mediated by the opioid system. Lisophosphatidic acid, which has been reported to be increased in patients with cholestasis and pruritus, has been described to cause scratching behavior that is prevented by an opiate antagonist in laboratory animals, suggesting an opioid-receptor mediated mechanism of scratching. In summary, evidence continues to support a role of the endogenous opioid system in the pathogenesis of the pruritus of cholestasis.
胆汁淤积性瘙痒是肝脏疾病的一种令人抓狂的并发症。阿片类物质能增加张力，这有助于解释胆汁淤积性瘙痒，因为阿片类拮抗剂可以改善这种症状。法尼醇 X 受体激动剂奥贝胆酸已被批准用于原发性胆汁性胆管炎的治疗，这种疾病的特点是胆汁淤积；这种药物与瘙痒有关，但其病因尚不清楚。在动物模型中，胆汁酸由于胆汁淤积而在体内积聚，据报道，它们会以阿片类物质依赖的方式通过 TGR5 受体引起搔抓行为，而奥贝胆酸也与 TGR5 结合，因此这种药物引起的瘙痒很可能是由阿片类系统介导的。据报道，在患有胆汁淤积和瘙痒的患者中，溶血磷脂酸增加，这种物质会导致搔抓行为，而在实验室动物中，阿片类拮抗剂可以预防这种搔抓行为，这表明存在一种阿片受体介导的搔抓机制。总之，越来越多的证据支持内源性阿片系统在胆汁淤积性瘙痒发病机制中的作用。
