TY - JOUR
T1 - TRP channels as novel players in the pathogenesis and therapy of itch
AU - Bíró, Tamás
AU - Tóth, Balázs I.
AU - Marincsák, Rita
AU - Dobrosi, Nóra
AU - Géczy, Tamás
AU - Paus, Ralf
N1 - Funding Information:
Grants, supports: Writing of this article was supported in part by Hungarian research grants (OTKA T049231 and K063153, ETT 480/2006) for T. Bíró and by a grant from Deutsche Forschungsgemeinschaft to R. Paus (Pa 345/11-2).
PY - 2007/8
Y1 - 2007/8
N2 - 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.
AB - 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.
KW - Itch
KW - Pruriceptive pruritus
KW - Pruritogens
KW - TRP channels
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U2 - 10.1016/j.bbadis.2007.03.002
DO - 10.1016/j.bbadis.2007.03.002
M3 - Review article
C2 - 17462867
AN - SCOPUS:34547609914
VL - 1772
SP - 1004
EP - 1021
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
SN - 0925-4439
IS - 8
ER -