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

被引:77
作者
Biro, Tamds
Toth, Balazs I.
Marincsak, Rita
Dobrosi, Nora
Geczy, Tamas
Paus, Ralf
机构
[1] Univ Debrecen, Dept Physiol, Med & Hlth Sci Ctr, Res Ctr Mol Med, H-4032 Debrecen, Hungary
[2] Univ Debrecen, Cell Physiol Res Grp, Hungarian Acad Sci, Med & Hlth Sci Ctr,Res Ctr Mol Med, H-4032 Debrecen, Hungary
[3] Med Univ Lubeck, Univ Hosp Schleswig Holstein, Dept Dermatol, D-23583 Lubeck, Germany
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2007年 / 1772卷 / 08期
基金
匈牙利科学研究基金会;
关键词
itch; pruriceptive pruritus; pruritogens; TRP channels;
D O I
10.1016/j.bbadis.2007.03.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (c) 2007 Elsevier B.V All rights reserved.
引用
收藏
页码:1004 / 1021
页数:18
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