TRP channels as novel players in the pathogenesis and therapy of itch

Tamás Bíró, Balázs I. Tóth, Rita Marincsák, Nóra Dobrosi, Tamás Géczy, Ralf Paus

Research output: Contribution to journalReview article

79 Scopus citations

Abstract

Itch (pruritus) is a sensory phenomenon characterized by a (usually) negative affective component and the initiation of a special behavioral act, i.e. scratching. Older studies predominantly have interpreted itch as a type of pain. Recent neurophysiological findings, however, have provided compelling evidence that itch (although it indeed has intimate connections to pain) rather needs to be understood as a separate sensory modality. Therefore, a novel pruriceptive system has been proposed, within which itch-inducing peripheral mediators (pruritogens), itch-selective receptors (pruriceptors), sensory afferents and spinal cord neurons, and defined, itch-processing central nervous system regions display complex, layered responses to itch. In this review, we begin with a current overview on the neurophysiology of pruritus, and distinguish it from that of pain. We then focus on the functional characteristics of the large family of transient receptor potential (TRP) channels in skin-coupled sensory mechanisms, including itch and pain. In particular, we argue that - due to their expression patterns, activation mechanisms, regulatory roles, and pharmacological sensitivities - certain thermosensitive TRP channels are key players in pruritus pathogenesis. We close by proposing a novel, TRP-centered concept of pruritus pathogenesis and sketch important future experimental directions towards the therapeutic targeting of TRP channels in the clinical management of itch.

Original languageEnglish (US)
Pages (from-to)1004-1021
Number of pages18
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1772
Issue number8
DOIs
StatePublished - Aug 1 2007
Externally publishedYes

Keywords

  • Itch
  • Pruriceptive pruritus
  • Pruritogens
  • TRP channels

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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