The molecular mechanism of cholestatic pruritus

Pruritus (= itch) is a common symptom of many different hepatobiliary diseases
being mostly associated with cholestasis. Pruritus is defined as an unpleasant
sensation with the desire or reflex to scratch the affected area of skin.
Depending on the severity of pruritus, quality of life may be remarkably
affected causing psychovegetative disorders and may even lead to suicide. Thus,
liver transplantation has been considered in cases of intractable pruritus.
Medical and interventional treatment options of cholestatic pruritus are
limited, reflecting the low pathophysiological understanding of this common
symptom on molecular basis. Therefore it would be eligible to map out the
mechanisms leading to itch, enabling the development of a more effective itch
therapy to the patient. In the last decade more information has become
available on potential mechanisms that lead to itch perception. While it has
become clear that pain and itch are transduced by separate nerve fibers, it is
also very well established that itch and pain perception are closely
intertwined processes. Thus, pain stimuli repress itch sensations, e.g.
scratching of the itching skin. Vice versa, in case pain signallling is
inhibited, e.g. by opioids or anaesthetics, pruritus may occur or aggravate.
It is our hypothesis that during cholestasis compounds that are normally
excreted into bile accumulate in plasma and act as direct or indirect
pruritogens by affecting receptor mediated signaling in neurons. It is our aim
to identify these compounds as well as the involved neuronal signaling
pathways.

The objective of this study is to identify direct or indirect pruritogens
accumulating during cholestasis and to analyze the involved neuronal signaling
pathways leading to the sensation of itch.

This is an open study carried out in 30 cholestatic patients and 30 cholestatic
patients with pruritus.

not applicable