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⺠(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.
ABSTRACT
PURPOSE: The purpose of the current study was to evaluate the effects of pregabalin administration as an adjunct to fentanyl-based intravenous patient-controlled analgesia on opioid consumption and postoperative pain following arthroscopic shoulder surgery. METHODS: In this randomized controlled trial, 60 adult patients undergoing arthroscopic shoulder surgery were randomly assigned to receive either pregabalin 150 mg (Pregabalin group, n = 30) or placebo (Control group, n = 30) one hour before anesthetic induction. The primary outcome was the cumulative amount of fentanyl consumption during 48 hr postoperatively. Secondary outcomes were pain intensity, the number of rescue analgesics administered, and adverse effects related to the analgesic regimen, which were serially assessed during 48 hr postoperatively. RESULTS: The cumulative fentanyl consumption during 48 hr postoperatively was significantly lower in the Pregabalin group than in the Control group ([1,126.0 (283.6) µg vs 1,641.4 (320.3) µg, respectively; mean difference, 515.4 µg; 95% confidence interval [CI], 359.0 to 671.8; P = < 0.001). Numeric rating scores for pain (0 to 10) were significantly lower in the Pregabalin group at six hours (mean difference, 2.9; 95% CI, 1.8 to 4.0), 24 hr (mean difference, 2.9; 95% CI, 1.9 to 3.8), and 48 hr (mean difference, 1.5; 95% CI, 0.6 to 2.3). The incidence of adverse effects related to the analgesic regimens, including nausea, sedation, and dizziness, were similar between the two groups. CONCLUSION: A preoperative dose of pregabalin 150 mg administered before arthroscopic shoulder surgery resulted in significant analgesic efficacy for 48 hr in terms of opioid-sparing effect and improved pain intensity scores without influencing complications. This trial was registered at: http://cris.nih.go.kr , number CT0000578.
