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Type: Journal article
Title: Low-dose endotoxin potentiates capsaicin-induced pain in man: evidence for a pain neuroimmune connection
Author: Hutchinson, M.
Bujis, M.
Tuke, S.
Kwok, Y.
Gentgall, M.
Williams, D.
Rolan, P.
Citation: Brain, Behavior, and Immunity, 2013; 30:3-11
Publisher: Academic Press Inc
Issue Date: 2013
ISSN: 0889-1591
Statement of
Mark R. Hutchinson, Mara Buijs, Jonathan Tuke, Yuen Hei Kwok, Melanie Gentgall, Desmond Williams, Paul Rolan
Abstract: Despite the wealth of evidence in animals that immune activation has a key role in the development and maintenance of chronic pain, evidence to support this in humans is scant. We have sought such evidence by examining the effect of a subtle immunological stimulus, low dose intravenous endotoxin, on the allodynia, hyperalgesia, flare and pain produced by intradermal capsaicin in healthy volunteers. Here we provide evidence of immune priming of this neuropathic-like pain response in humans. Specifically, in 12 healthy volunteers, activation of Toll-Like Receptor 4 by endotoxin (0.4ng/kg IV) caused significant 5.1-fold increase in the 90-min integral of areas of capsaicin-induced allodynia (95% CI 1.3-9.1), 2.2-fold increase in flare (95% CI 1.9-2.6) and 1.8-fold increase in hyperalgesia (95% CI 1.1-2.5) following 50μg intradermal capsaicin injected into the forearm 3.5h after endotoxin. These data demonstrate clinically a significant role for the neuroimmune pain connection in modifying pain, thus providing evidence that immune priming may produce pain enhancement in humans and hence offer a novel range of pharmacological targets for anti-allodynics and/or analgesics. Additionally, the simplicity of the model makes it suitable as a test-bed for novel immune-targeted pain therapeutics.
Keywords: Endotoxin
Chronic pain
Rights: Copyright © 2013 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.bbi.2013.03.002
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Appears in Collections:Aurora harvest
Pharmacology publications

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