Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Enhanced Expression of TREK-1 Is Related with Chronic Constriction Injury of Neuropathic Pain Mouse Model in Dorsal Root Ganglion

  • Han, Hyo Jo (Department of Anesthesiology and Pain Medicine, CHA Bundang Medical Center, CHA University) ;
  • Lee, Seung Wook (Division of Natural Science, Ajou University) ;
  • Kim, Gyu-Tae (Departments of Physiology and Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Kim, Eun-Jin (Departments of Physiology and Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Kwon, Byeonghun (Department of Anesthesiology and Pain Medicine, CHA Bundang Medical Center, CHA University) ;
  • Kang, Dawon (Departments of Physiology and Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Kim, Hyun Jeong (Department of Dental Anesthesiology and Dental Research Institute, School of Dentistry, Seoul National University) ;
  • Seo, Kwang-Suk (Department of Dental Anesthesiology and Dental Research Institute, School of Dentistry, Seoul National University)
  • Received : 2016.02.18
  • Accepted : 2016.03.31
  • Published : 2016.05.01
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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.

Keywords

References

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