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

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.

Curcumin Diglutaric Acid, a Prodrug of Curcumin Reduces Pain Hypersensitivity in Chronic Constriction Injury of Sciatic Nerve Induced-Neuropathy in Mice

“…In the present study, CurDG, at the lowest dose tested (equimolar to 25 mg/kg curcumin), demonstrated a significant reduction in both mechanical and thermal pain hypersensitivities compared to the CCI-control group ( p < 0.05). Though many studies reported the baseline PWT of mice lying below 1.4 g, the baseline PWT value of ≈ 4 g, obtained in this study, was consistent with several previous studies [ 38 , 39 ]. Moreover, as per the AUC data obtained for the entire time-course, a dose-dependent reduction in both mechanical and thermal pain-hypersensitivities was observed with 25, 50, and 100 CurDG ( p < 0.05), while 200 CurDG showed comparable analgesia with 100 CurDG.…”

GI‐530159, a novel, selective, mechanosensitive two‐pore‐domain potassium (K2P) channel opener, reduces rat dorsal root ganglion neuron excitability

“…TREK1 channels are expressed in both small‐sized and medium‐sized dorsal root ganglion (DRG) neurons where they are often co‐localized with excitatory transient receptor potential cation channel subfamily V member 1 (TRPV1) channels (Maingret et al ., ; Talley et al ., ; Alloui et al ., ; Dedman et al ., ; Marsh et al ., ), and enhanced expression of TREK1 is seen in DRG neurons in a mouse model of neuropathic pain (Han et al ., ). TREK1 knockout mice are more sensitive than wild‐type mice to painful heat sensations near the threshold between non‐painful and painful heat (Alloui et al ., ).…”

Characterization of temperature-sensitive leak K+ currents and expression of TRAAK, TREK-1, and TREK2 channels in dorsal root ganglion neurons of rats

“…It has been shown that mRNAs of TREK-1 channels are present in rat dorsal root ganglia (DRG) and their levels are increased after partial bladder outlet obstruction [ 27 ]. TREK-1 expression is also increased in mouse DRGs following chronic constriction nerve injury [ 11 ]. Thermal K2P channels are found to be upregulated in fast blue-labeled thoracolumbar and lumbosacral somata after inflaming the prostate with intraprostate injection of zymosan [ 26 ].…”