Spinal voltage-gated potassium channel Kv1.3 contributes to neuropathic pain via promotion of microglial M1 polarization and activation of the NLRP3 inflammasome

Xiaoman, Yuan, Han, Siyi, Manyande, Anne ORCID: https://orcid.org/0000-0002-8257-0722, Gao, Feng, Wang, Jie, Zhang, Wen and Tian, Xuebi (2022) Spinal voltage-gated potassium channel Kv1.3 contributes to neuropathic pain via promotion of microglial M1 polarization and activation of the NLRP3 inflammasome. European Journal of Pain. ISSN 1090-3801

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Abstract

Background: Studies have shown that activation of microglia is the main mechanism of neuropathic pain. The Kv1.3 channel is a novel therapeutic target for treating neuroinflammatory disorders due to its crucial role in subsets of microglial cells. As such, it may be involved in the processes of neuropathic pain, however, whether Kv1.3 plays a role in neuroinflammation following peripheral nerve injury is unclear. Methods: The spared nerve injury model (SNI) was used to establish neuropathic pain. Western blot and immunofluorescence were used to examine the effect of Kv1.3 in the SNI rats. PAP-1, a Kv1.3 specific blocker was administered to alleviate neuropathic pain in the SNI rats. Results: Neuropathic pain and allodynia occurred after SNI, the levels of M1 (CD68, iNos) and M2 (CD206, Arg-1) phenotypes were up-regulated in the spinal cord, and the protein levels of NLRP3, caspase-1 and IL-1β were also increased. Pharmacological blocking of Kv1.3 with PAP-1 alleviated hyperpathia induced by SNI. Meanwhile, intrathecal injection of PAP-1 reduced M1 polarization and decreased NLRP3, caspase-1, and IL-1β expressions of protein levels. Conclusion: Our research indicates that the Kv1.3 channel in the spinal cord contributes to neuropathic pain by promoting microglial M1 polarization and activating the NLRP3 inflammasome.

Item Type: Article
Identifier: 10.1002/ejp.2059
Additional Information: This is the peer reviewed version of the following article: [Xiaoman, Y., Han, S., Manyande, A., Gao, F., Wang, J., Zhang, W. and Tian, X. (2022), Spinal voltage-gated potassium channel Kv1.3 contributes to neuropathic pain via promotion of microglial M1 polarization and activation of the NLRP3 inflammasome. Eur J Pain. Accepted Author Manuscript. https://doi.org/10.1002/ejp.2059], which has been published in final form at https://doi.org/10.1002/ejp.2059. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
Keywords: microglial activition, M1 polarization, neuropathic pain, Kv1.3, the NLRP3 inflammasome, neuroinflammation
Subjects: Medicine and health
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Depositing User: Anne Manyande
Date Deposited: 29 Nov 2022 10:36
Last Modified: 05 Dec 2022 14:48
URI: https://repository.uwl.ac.uk/id/eprint/9659

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