Relationship between remifentanil-induced hyperalgesia and function of nitrated glutamate transportor-1 and glutamine synthetase in spinal cord of rats with incisional pain

Abstract

Objective To investigate the relationship remifentanil-induced hyperalgesia and function of nitrated glutamate transportor-1 (GLT-1) and glutamine synthetase (GS) in the spinal cord of rats with incisional pain. Methods Thirty-two male Sprague-Dawley rats, weighing 260-280 g, aged 2-3 months, in which caudal catheters were successfully implanted, were divided into 4 groups (n=8 each) using a random number table method: control group (group C), incisional pain group (group I), remifentanil group (group R) and remifentanil plus incisional pain group (group RI). Normal saline was intravenously infused for 60 min at 0.1 ml·kg-1·min-1 in group C. The model of incisional pain was established, and normal saline was simultaneously infused for 60 min via the tail vein at 0.1 ml·kg-1·min-1 in group I. Remifentanil was infused for 60 min via the tail vein at 1.0 μg· kg-1·min-1 in group R. The model of incisional pain was established, and remifentanil was infused for 60 min via the tail vein at 1.0 μg· kg-1·min-1 in group RI.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before infusion of remifentanil or normal saline (T0) and at 2, 6, 24 and 48 h after infusion (T1-4). The rats were sacrificed after the last measuremnet of pain threshold, and the L4-6 segment of the spinal cord was removed for determination of the expression of GLT-1 and GS (by Western blot) and expression of nitrated GLT-1 (nGLT-1) and nitrated GS (nGS) (by Western blot). Ratios of nGLT-1/GLT-1 and nGS/GS were calculated. Results Compared with group C, the MWT was significantly decreased and TWL was shortened at T1-4, the expression of GLT-1 and GS was down-regulated, the expression of nGLT-1 and nGS was up-regulated, and ratios of nGLT-1/GLT-1 and nGS/GS were increased in I, R and RI groups (P<0.05). Compared with group I and group R, the MWT was significantly decreased and TWL was shortened at T1-4, the expression of GLT-1 and GS was down-regulated, the expression of nGLT-1 and nGS was up-regulated, and ratios of nGLT-1/GLT-1 and nGS/GS were increased in group RI (P<0.05). Conclusion The mechanism of remifentanil-induced hyperalgesia may be related to impaired function of GLT-1 and GS in the spinal cord of rats with incisional pain. Key words: Piperidines; Hyperalgesia; Pain, postoperative; Glutamate plasma membrane transport proteins; Glutamate-ammonia ligase; Spinal cord