Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093, USA.
Sci Signal. 2011 Aug 23;4(187):er3.
The skin is the largest sensory organ of the body. It is innervated by a diverse array of primary sensory neurons, including a heterogeneous subset of unmyelinated afferents called C fibers. C fibers, sometimes classified as nociceptors, can detect various painful stimuli, including temperature extremes. However, it is increasingly evident that these afferents respond to various pruritic stimuli and transmit information to the brain that is perceived as itch; this can subsequently drive scratching behavior. Although itch and pain are distinct sensations, they are closely related and can, under certain circumstances, antagonize each other. However, it is not clear precisely when, where, and how the processes generating these two sensations originate and how they are dissociated. Clues have come from the analysis of the activities of specific ligands and their receptors. New data indicate that specific pruritic ligands carrying both itch and pain information are selectively recognized by different G protein–coupled receptors (GPCRs), and this information may be transduced through different intracellular circuits in the same neuron. These findings raise questions about the intracellular mechanisms that preprocess and perhaps encode GPCR-mediated signals.
皮肤是人体最大的感觉器官。它由多种主要感觉神经元支配，包括称为 C 纤维的无髓传入纤维的异质子集。C 纤维，有时被归类为伤害感受器，可检测到各种疼痛刺激，包括极端温度。然而，越来越明显的是，这些传入纤维对各种瘙痒刺激有反应，并将被感知为瘙痒的信息传递给大脑；这随后会驱动抓挠行为。尽管瘙痒和疼痛是不同的感觉，但它们密切相关，在某些情况下可以相互拮抗。然而，目前尚不清楚产生这两种感觉的过程何时、何地以及如何起源，以及它们是如何分离的。这些线索来自对特定配体及其受体活性的分析。新的数据表明，携带瘙痒和疼痛信息的特定瘙痒配体被不同的 G 蛋白偶联受体 (GPCR) 特异性识别，并且该信息可能通过同一神经元中的不同细胞内回路进行转导。这些发现提出了关于细胞内机制的问题，这些机制可能对 GPCR 介导的信号进行预处理，甚至编码。
