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Nociceptors Are Interleukin-1β Sensors

A cardinal feature of inflammation is heightened pain sensitivity at the site of the inflamed tissue. This results from the local release by immune and injured cells of nociceptor sensitizers, including prostaglandin E2, bradykinin, and nerve growth factor, that reduce the threshold and increase the excitability of the peripheral terminals of nociceptors so that they now respond to innocuous stimuli: the phenomenon of peripheral sensitization. We show here that the proinflammatory cytokine interleukin-1β (IL-1β), in addition to producing inflammation and inducing synthesis of several nociceptor sensitizers, also rapidly and directly activates nociceptors to generate action potentials and induce pain hypersensitivity. IL-1β acts in a p38 mitogen-activated protein kinase (p38 MAP kinase)-dependent manner, to increase the excitability of nociceptors by relieving resting slow inactivation of tetrodotoxin-resistant voltage-gated sodium channels and also enhances persistent TTX-resistant current near threshold. By acting as an IL-1β sensor, nociceptors can directly signal the presence of ongoing tissue inflammation.

Authors: Binshtok AM, Wang H, Zimmermann K, Amaya F, Vardeh D, Shi L, Brenner G, Ji RRC, Bean BP, Woolf CJ, Samad TA

Year of publication: 2008

Journal: Journal of Neuroscience, 28 (52) 14062-14073

Link to publication:

https://doi.org/10.1523/JNEUROSCI.3795-08.2008

Labs:

Alexander Binshtok

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