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Inhibition of the potassium channel KCa3.1 by senicapoc reverses tactile allodynia in rats with peripheral nerve injury

Neuropathic pain is a debilitating, chronic condition with a significant unmet need for effective treatment options. Recent studies have demonstrated that in addition to neurons, non-neuronal cells such as microglia contribute to the initiation and maintenance of allodynia in rodent models of neurop...

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Published in:European journal of pharmacology 2017-01, Vol.795, p.1-7
Main Authors: Staal, Roland G.W., Khayrullina, Tanzilya, Zhang, Hong, Davis, Scott, Fallon, Shaun M., Cajina, Manuel, Nattini, Megan E., Hu, Andrew, Zhou, Hua, Poda, Suresh Babu, Zorn, Stevin, Chandrasena, Gamini, Dale, Elena, Cambpell, Brian, Biilmann Rønn, Lars Christian, Munro, Gordon, Mӧller, Thomas
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container_title European journal of pharmacology
container_volume 795
creator Staal, Roland G.W.
Khayrullina, Tanzilya
Zhang, Hong
Davis, Scott
Fallon, Shaun M.
Cajina, Manuel
Nattini, Megan E.
Hu, Andrew
Zhou, Hua
Poda, Suresh Babu
Zorn, Stevin
Chandrasena, Gamini
Dale, Elena
Cambpell, Brian
Biilmann Rønn, Lars Christian
Munro, Gordon
Mӧller, Thomas
description Neuropathic pain is a debilitating, chronic condition with a significant unmet need for effective treatment options. Recent studies have demonstrated that in addition to neurons, non-neuronal cells such as microglia contribute to the initiation and maintenance of allodynia in rodent models of neuropathic pain. The Ca2+- activated K+ channel, KCa3.1 is critical for the activation of immune cells, including the CNS-resident microglia. In order to evaluate the role of KCa3.1 in the maintenance of mechanical allodynia following peripheral nerve injury, we used senicapoc, a stable and highly potent KCa3.1 inhibitor. In primary cultured microglia, senicapoc inhibited microglial nitric oxide and IL-1β release. In vivo, senicapoc showed high CNS penetrance and when administered to rats with peripheral nerve injury, it significantly reversed tactile allodynia similar to the standard of care, gabapentin. In contrast to gabapentin, senicapoc achieved efficacy without any overt impact on locomotor activity. Together, the data demonstrate that the KCa3.1 inhibitor senicapoc is effective at reducing mechanical hypersensitivity in a rodent model of peripheral nerve injury.
doi_str_mv 10.1016/j.ejphar.2016.11.031
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ispartof European journal of pharmacology, 2017-01, Vol.795, p.1-7
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source Elsevier
subjects Calcium-activated potassium channel
Chronic constriction injury
Gabapentin
ICA-17043
KCa3.1
KCNN4
Microglia
Neuropathic pain
Senicapoc
Tactile allodynia
Von Frey
title Inhibition of the potassium channel KCa3.1 by senicapoc reverses tactile allodynia in rats with peripheral nerve injury
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