Neural processing of itch

Abstract

While considerable effort has been made to investigate the neural mechanisms of pain, much less effort has been devoted to itch, at least until recently. However, itch is now gaining increasing recognition as a widespread and costly medical and socioeconomic issue. This is accompanied by increasing interest in the underlying neural mechanisms of itch, which has become a vibrant and rapidly-advancing field of research. The goal of the present forefront review is to describe the recent progress that has been made in our understanding of itch mechanisms.

Keywords: 5-HT; 5-HT receptor subtype 2; 5-HT2; 5-hydroxytryptamine (serotonin); AITC; BAM8–22; BLT; DRG; ET-1; ETA-1; G protein-coupled bile acid receptor 1 (GPBAR1); GRP; GRPR; Gastrin-releasing peptide; Gastrin-releasing peptide receptor; H1R; IB4; IL-31; Interleukin 31; K2P; Kv; LPA; LT; LTB4; LTB4 receptor; LTMRs; LTP; MI; MOR1D; Mas-related G-protein-coupled receptor; Mrgpr; NGF; NK-1; NS; Nppb; Npra; OSMR; PAF; PAG; PAR; Platelet-activating factor; Rho-ROCK; Rho-associated protein kinase; SP; SPC; STT; TGR5; TLR3; TLR7; TR4; TRPA1; TRPV1; TXA2; VGLUT2; Vc; WDR; allyl isothiocyanate; bovine adrenal medullary peptide 8–22; dorsal root ganglion; endothelin receptor A-1; endothelin-1; histamine receptor-1; isolectin B4; itch; leukotriene B4; long-term potentiation; low threshold; low-threshold mechanoreceptors; lysophosphatidic acid; mechanically insensitive; morphine receptor-1D isoform; natriuretic peptide receptor A; natriuretic polypeptide B; nerve growth factor; neurokinin-1 receptor; nociceptive specific; oncostatin M receptor; periaqueductal gray; protease-activated receptor; pruritogens; pruritus; scratching behavior; sphingosylphosphorylcholine; spinal cord; spinothalamic tract; substance P; testicular orphan nuclear receptor-4; thromboxane A2; toll-like receptor 3; toll-like receptor 7; transient receptor potential ankyrin 1; transient receptor potential vanilloid 1; trigeminal caudalis; trigeminal subnucleus caudalis; two-pore-domain potassium channels; vesicular glutamate transporter-2; voltage-gated potassium channel; wide dynamic range.

Fig. 1

Schematic diagram of excitatory circuits for itch. Dashed line is cross-section of spinal cord dorsal horn. Upper right shows cross-section through skin. + denotes excitatory synapse.

Fig. 2

Schematic diagram of inhibitory spinal circuits for itch. +, − denote excitatory and inhibitory synapses, respectively.

Fig. 3

Schematic diagram of mechanisms underlying itch sensitization. 1. Peripheral sensitization may occur through PAR-2. 2. Central sensitization may occur through TLR3. 3. Dysfunction of itch inhibitory circuits may contribute to itch sensitization. See text for details.