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Itch Control by Toll-Like Receptors

  • Chapter
Pharmacology of Itch

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 226))

Abstract

Toll-like receptors (TLRs) are cellular sensors designed to recognize molecular danger signals associated with exogenous or endogenous threats. Their activation leads to initiation of the host’s immune responses in order to remove or contain the danger. However, one of the most effective methods of defense against invading pathogens and parasites is itch. The perception of itch elicits the rapid defensive action to scratch, which can remove the offending pathogen or parasite before infection can occur. Recent findings show that TLRs such as TLR3, TLR4, and TLR7 are expressed in a subset of pruriceptive/nociceptive neurons in the dorsal root and trigeminal ganglion providing a direct link between TLR activation and itch. Activation of neuronal TLRs can initiate itch sensation by coupling with ion channels. Furthermore, TLRs are expressed in skin cells and glial cells in the spinal cord to regulate inflammation and neuroinflammation in chronic itch. Thus, identification of the role of TLRs in neurons, skin cells, and glial cells may provide new targets for the treatment of chronic itch, a common clinical problem associated with skin diseases, systemic diseases, and metabolic disorders, for which current treatments are far from sufficient.

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Abbreviations

5HT:

Serotonin

BDNF:

Brain-derived neurotrophic factor

CCL2:

Chemokine ligand 2 (MCP-1)

CGRP:

Calcitonin gene-related peptide

CNS:

Central nervous system

COX-2:

Cyclooxygenase 2

CXCL:

Chemokine (C-X-C motif) ligand

DAMPs:

Danger-associated molecular patterns

DRG:

Dorsal root ganglia

dsRNA:

Double-stranded RNA

ERK:

Extracellular signal-regulated kinase

ET-1:

Endothelin-1

GRP:

Gastrin-releasing peptide

GRPR:

Gastrin-releasing peptide receptor

IL-1β:

Interleukin-1beta

IRAKs:

IL-1R-associated kinases

IRFs:

Interferon regulatory factors

JNK:

c-Jun N-terminal kinase

LPS:

Lipopolysaccharide

LTP:

Long-term potentiation

MAPK:

Mitogen-activated protein kinase

MCP-1:

Monocyte chemoattractant protein 1 (CCL2)

miRNA:

Microribonucleic acid

mRNA:

Messenger ribonucleic acid

NF-kB:

Nuclear factor-kappa B

NGF:

Nerve growth factor

NO:

Nitric oxide

Nppb:

Natriuretic polypeptide b

PAMPs:

Pathogen-associated molecular patterns

PAR2:

Protease-activated receptor 2

PGE2:

Prostaglandin E2

Poly I:C:

Polyinosinic:polycytidylic acid

RIP-1:

Receptor-interacting protein 1

sEPSCs:

Spontaneous excitatory postsynaptic currents

ssRNA:

Single-stranded RNA

TIR:

Toll–interleukin-1 receptor

TLRs:

Toll-like receptors

TNF-α:

Tumor necrosis factor alpha

TRAF6:

Tumor necrosis factor receptor-associated factor 6

TRPV1:

Transient receptor potential vanilloid subtype 1

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Acknowledgements

This work is supported by NIH grants R01DE17794, R01DE22743, and R01NS89479.

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Authors and Affiliations

  1. Departments of Anesthesiology and Neurobiology, Duke University Medical Center, Durham, NC, 27710, USA

    Sarah Taves & Ru-Rong Ji

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  1. Sarah Taves
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  2. Ru-Rong Ji
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Correspondence to Ru-Rong Ji .

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Editors and Affiliations

  1. Department of Pharmacology Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, Pennsylvania, USA

    Alan Cowan

  2. Department of Dermatology, Temple University School of Medicine, Philadephia, Pennsylvania, USA

    Gil Yosipovitch

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Taves, S., Ji, RR. (2015). Itch Control by Toll-Like Receptors. In: Cowan, A., Yosipovitch, G. (eds) Pharmacology of Itch. Handbook of Experimental Pharmacology, vol 226. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-44605-8_7

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