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Adv Exp Med Biol. 2016;904:23-32. doi: 10.1007/978-94-017-7537-3_2.

Allergic Contact Dermatitis: A Model of Inflammatory Itch and Pain in Human and Mouse.

Author information

1
Department of Anesthesiology, Yale University School of Medicine, 330 Cedar St, New Haven, CT, 06510, USA. Robert.LaMotte@yale.edu.

Abstract

This chapter is an overview of published observations from our laboratory on the psychophysics and neurobiology of the persistent itch and pain of allergic contact dermatitis (ACD). ACD is a clinically significant problem with many features characteristic of other pruritic disorders. Our approach was to produce ACD experimentally in humans and in the mouse. The goal was to use the mouse as an animal model for investigating the peripheral neural mechanisms of itch and pain of ACD in humans. Humans and mice were each sensitized by cutaneous topical application of squaric acid dibutyl ester, a hapten not encountered in the environment. Subsequent challenge at another cutaneous site produced local inflammation ("ACD") with humans reporting persistent itch (lasting up to a week) and mice exhibiting persistent itch- and pain-like behaviors directed toward the ACD site. Enhanced mechanically evoked itch and pain in surrounding skin in humans were reversibly blocked by numbing the ACD site with cold, suggesting dependence on ongoing activity from the site. In mice, in vivo recordings revealed spontaneous activity in a subset of pruriceptive, mechanoheat-sensitive nociceptors with unmyelinated axons innervating the ACD site. These and a larger subpopulation of acutely dissociated small-diameter neurons innervating the ACD site exhibited an upregulation of the receptor CXCR3 and excitatory responses to one of its ligands, the chemokine CXCL10 (IP-10) that contributes to the pathogenesis of ACD. Preliminary findings point to possible therapeutic targets that could be investigated in inflammatory itch disorders in humans.

KEYWORDS:

Dermatitis; Itch; Nociceptor; Pain

PMID:
26900060
PMCID:
PMC4910628
DOI:
10.1007/978-94-017-7537-3_2
[Indexed for MEDLINE]
Free PMC Article
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