Biomol Ther.  2016 May;24(3):252-259. 10.4062/biomolther.2016.038.

Enhanced Expression of TREK-1 Is Related with Chronic Constriction Injury of Neuropathic Pain Mouse Model in Dorsal Root Ganglion

Affiliations
  • 1Department of Anesthesiology and Pain Medicine, CHA Bundang Medical Center, CHA University, Seongnam 13496, Republic of Korea.
  • 2Division of Natural Science, Ajou University, Suwon 16499, Republic of Korea.
  • 3Departments of Physiology and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 52727, Republic of Korea. stone90@snu.ac.kr
  • 4Department of Dental Anesthesiology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea. stone90@snu.ac.kr

Abstract

Neuropathic pain is a complex state showing increased pain response with dysfunctional inhibitory neurotransmission. The TREK family, one of the two pore domain K+ (K2P) channel subgroups were focused among various mechanisms of neuropathic pain. These channels influence neuronal excitability and are thought to be related in mechano/thermosensation. However, only a little is known about the expression and role of TREK-1 and TREK-2, in neuropathic pain. It is performed to know whether TREK-1 and/or 2 are positively related in dorsal root ganglion (DRG) of a mouse neuropathic pain model, the chronic constriction injury (CCI) model. Following this purpose, Reverse Transcription Polymerase Chain Reaction (RT-PCR) and western blot analyses were performed using mouse DRG of CCI model and compared to the sham surgery group. Immunofluorescence staining of isolectin-B4 (IB4) and TREK were performed. Electrophysiological recordings of single channel currents were analyzed to obtain the information about the channel. Interactions with known TREK activators were tested to confirm the expression. While both TREK-1 and TREK-2 mRNA were significantly overexpressed in DRG of CCI mice, only TREK-1 showed significant increase (~9 fold) in western blot analysis. The TREK-1-like channel recorded in DRG neurons of the CCI mouse showed similar current-voltage relationship and conductance to TREK-1. It was easily activated by low pH solution (pH 6.3), negative pressure, and riluzole. Immunofluorescence images showed the expression of TREK-1 was stronger compared to TREK-2 on IB4 positive neurons. These results suggest that modulation of the TREK-1 channel may have beneficial analgesic effects in neuropathic pain patients.

Keyword

Neuropathic pain; Chronic constriction injury model; Dorsal root ganglion; Isolectin-B4; TREK-1 expression

MeSH Terms

Animals
Blotting, Western
Constriction*
Diagnosis-Related Groups
Fluorescent Antibody Technique
Ganglia, Spinal*
Humans
Hydrogen-Ion Concentration
Mice*
Neuralgia*
Neurons
Polymerase Chain Reaction
Reverse Transcription
Riluzole
RNA, Messenger
Spinal Nerve Roots*
Synaptic Transmission
RNA, Messenger
Riluzole
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