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

Abstract

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.

• Authors: Guadalupe García, Vladimir A Martínez-Rojas, Janet Murbartián
• Journal: Behavioural brain research (Behav Brain Res) Vol. 413 Pg. 113446 (09 10 2021) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 34224765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• (5,6,7,8-tetrahydronaphthalen-1-yl)-(2-(1H-tetrazol-5-yl)phenyl)amine
• Disinfectants
• Peptides
• Potassium Channels, Tandem Pore Domain
• Tetrahydronaphthalenes
• Tetrazoles
• potassium channel protein TREK-1
• spadin peptide
• Formaldehyde

Topics

• Animals
• Disease Models, Animal
• Disinfectants (pharmacology)
• Female
• Formaldehyde (pharmacology)
• Ganglia, Spinal (drug effects, metabolism)
• Hyperalgesia (chemically induced, drug therapy, metabolism)
• Male
• Nociceptive Pain (chemically induced, drug therapy, metabolism)
• Peptides (pharmacology)
• Potassium Channels, Tandem Pore Domain (antagonists & inhibitors, drug effects, metabolism)
• Rats
• Rats, Wistar
• Spinal Cord (drug effects, metabolism)
• Tetrahydronaphthalenes (pharmacology)
• Tetrazoles (pharmacology)