Mediators of XXXX during @entity1448 .

@entity1 @entity4990 @entity6579 @entity4991 @entity19 @entity409 @entity111 @entity1448 @entity23927 @entity3645
PURPOSE OF REVIEW: @entity111 is a frequent symptom in @entity1 with @entity409 . Itching may be excruciating, may seriously impair quality of life and even induce suicidal ideation in the most severe cases. RECENT FINDINGS: The molecular mechanism of itch signal transduction in @entity1448 is largely unclear. It may be caused or potentiated by compounds that accumulate in the circulation during @entity1448 , which either directly or indirectly affect signalling in itch fibres. In the past, @entity3645 and endogenous opioids have been proposed but never been proven to be key factors in itch perception during @entity1448 . We have performed a screen for compounds in plasma from @entity1 with various cholestatic conditions for their capacity to activate neuronal cell lines. In these sera, we could identify a potent neuronal activator as @entity4990 ( @entity4991 ). @entity4991 is a very potent signalling phospholipid that can activate cells through various @entity4991 receptors. Quite strikingly, samples from itchy cholestatic @entity1 contained higher amounts of @entity4991 . These increased levels of @entity4991 turned out to be caused by elevated levels of serum @entity23927 , the enzyme that converts @entity6579 into @entity4991 . This is a striking finding, as @entity23927 has never been connected to itch perception thus far. We have also shown that @entity4991 , when injected intradermally, caused scratching behaviour in @entity19 . SUMMARY: On the basis of our results, we hypothesize that during @entity1448 expression of @entity23927 is induced, which gives rise to increased local formation of @entity4991 near unmyelinated nerve endings of itch fibres. @entity4991 activates these neurons through one of the @entity4991 receptors, which in turn potentiates action potentials along itch fibres leading to the perception of @entity111 .
