STUDIES OF THE OPIATE SYSTEM IN CHOLESTATIC LIVER DISEASE

阿片系统在胆汁淤积性肝病中的研究

• 批准号: 3876442
• 负责人: E A JONES
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3876442
• 关键词: bile obstruction; drug administration routes; human subject; human therapy evaluation; inhibitor /antagonist; laboratory rat; liver cirrhosis; medical complication; naloxone; naltrexone; neuropeptide receptor; opioid receptor; pruritis; skin disorder chemotherapy

A new system for continuously quantitating scratching activity has been devised. This system permits objective quantitative studies of the effectiveness of therapies for the pruritus of cholestasis to be undertaken. Using this system naloxone infusions have been shown to decrease scratching activity by about 50% in patients with pruritus due to primary biliary cirrhosis, suggesting that the opiate system may be implicated in the mediation of the pruritus of cholestasis . Rats with acute cholestasis due to bile duct ligation have been shown to have a mild analgesic state as evaluated with the tail flick assay. This analgesia can be reversed by naloxone. These findings are consistent with the syndrome of cholestasis being associated with increased opiatergic tone and raise the possibility that certain complications of cholestasis, such as pruritus, may be mediated by central opiate receptors and alleviated by the administration of opiate receptor antagonists that are effective when given orally (e.g.nalmefene).

一个新的系统，连续定量抓挠活动已被 设计的这一系统允许客观的定量研究， 胆汁淤积瘙痒症治疗方法的有效性 进行。使用该系统，纳洛酮输注已被证明 减少瘙痒患者的抓挠活动约50%， 原发性胆汁性肝硬化，表明阿片系统可能是 涉及胆汁淤积瘙痒的调节。大鼠 由于胆管结扎引起的急性胆汁淤积已经显示具有轻度的 用甩尾试验评价的镇痛状态。这种镇痛可以 被纳洛酮逆转这些发现与 胆汁淤积与阿片张力增加有关， 胆汁淤积的某些并发症，如瘙痒症， 可能是由中枢阿片受体介导的， 当给予有效的阿片受体拮抗剂时， 口服（例如纳美芬）。