TREK-1 potassium channels participate in acute and long-lasting nociceptive hypersensitivity induced by formalin in rats.

Autor: García G; Departamento de Farmacobiología, Cinvestav, Sede Sur, Mexico City, Mexico. Electronic address: garcia.p.gpe@gmail.com., Martínez-Rojas VA; Departamento de Farmacobiología, Cinvestav, Sede Sur, Mexico City, Mexico. Electronic address: vlalx.mr@gmail.com., Murbartián J; Departamento de Farmacobiología, Cinvestav, Sede Sur, Mexico City, Mexico. Electronic address: murbartian@cinvestav.mx.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2021 Sep 10; Vol. 413, pp. 113446. Date of Electronic Publication: 2021 Jul 03.
DOI: 10.1016/j.bbr.2021.113446
Abstrakt: TREK-1 channels are expressed in small nociceptive dorsal root ganglion (DRG) neurons where they participate in acute inflammatory and neuropathic pain. However, the role of TREK-1 in persistent pain is not well understood. The aim of this study was to investigate the local peripheral and spinal participation of TREK-1 in formalin-induced acute and long-lasting nociceptive hypersensitivity. Local peripheral or intrathecal pre-treatment with spadin, selective blocker of TREK-1, increased acute flinching behavior and secondary mechanical allodynia and hyperalgesia behavior observed 6 days after formalin injection. Local peripheral or intrathecal pre-treatment with BL-1249, selective opener of TREK-1, decreased long-lasting secondary mechanical allodynia and hyperalgesia induced by formalin. Pre-treatment with BL-1249 prevented the pro-nociceptive effect of spadin on acute nociception and long-lasting mechanical allodynia and hyperalgesia in rats. Pre-treatment with two recombinant channels that produce a high TREK-1 current, S300A and S333A (non-phosphorylated state of TREK-1), reduced formalin-induced acute pain and long-lasting mechanical allodynia and hyperalgesia. Besides, post-treatment with S300A, S333A or BL-1249 reversed long-lasting mechanical allodynia and hyperalgesia induced by formalin. Formalin increased TREK-1 expression at 1 and 6 days in DRG and dorsal spinal cord in rats, whereas that it increased c-fos expression at the DRG. Intrathecal repeated transfection of rats with S300A and S333A or injection with BL-1249 reduced formalin-induced enhanced c-fos expression. Data suggest that TREK-1 activity at peripheral and spinal sites reduces neuronal excitability in the process of acute and long-lasting nociception induced by formalin in rats.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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