STUDIES OF THE OPIATE SYSTEM IN CHOLESTATIC LIVER DISEASE

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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).