Hypothesis the pruritus of cholestasis: From bile acids to opiate agonists

✍ Scribed by Dr. E. Anthony Jones; Nora V. Bergasa

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 551 KB
• Volume: 11
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840110526

✦ Synopsis

Cholestasis of any origin can be complicated by distressing pruritus. Evidence that bile acid retention contributes significantly to this form of pruritus is unconvincing. However, endogenous opiate agonist ligands (e.g., enkephalins) also accumulate in cholestasis, and pruritus is a recognized side effect of opiate agonist drugs such as morphine. In patients with chronic cholestasis, increased stimulation of the opiate system by agonist ligands is suggested by the precipi tation of an opiate withdrawal-like syndrome by a potent opiate receptor antagonist and the amelioration of pruritus by two opiate receptor antagonists. We postulate that a major factor contributing to the pruritus of cholestasis is increased availability of opiate agonist ligands at opiate receptors in the brain.

THE PRURITUS OF CHOLESTASIS

AND BILE ACIDS Cholestasis, or impaired hepatocellular secretion of bile, is a complication of chronic progressive liver disease. It is characterized by an accumulation in plasma of substances that are normally secreted into the bile such as bilirubin, bile acids and cholesterol (1). A distressing symptom in many patients with chronic cholestasis is pruritus. This symptom tends not to be readily relieved by scratching and is often a major problem to manage. It may be persistent or intermittent. It may also be generalized or localized to particular parts of the body. Its severity can vary from mild, with no interference with normal activities; to moderate, with disturbance of sleep; to severe and intractable. Unrelieved pruritus can be an indication for liver transplantation (2).

The pathogenesis of the pruritus of cholestasis is unknown. It has been suggested that the symptom may arise as a result of an interaction between nerve endings in the skin and one or more substances retained in