Effect of dexmedetomidine on trafficking of N-methyl-D-aspartate receptors in spinal dorsal horn neurons during remifentanil-induced hyperalgesia in rats with incisional pain

Abstract

Objective To investigate the effect of dexmedetomidine on trafficking of N-methyl-D-aspartate(NMDA)receptors in spinal dorsal horn neurons during remifentanil-induced hyperalgesia in the rats with incisional pain. Methods Twenty-four male Sprague-Dawley rats, aged 2-3 months, weighing 240-260 g, were randomly divided into 3 groups(n=8 each)using a random number table: control group(group C), remifentanil + incisional pain group(group R+ I), and dexmedetomidine + remifentanil + incisional pain group(group D+ R+ I). A 1 cm longitudinal incision was made in the plantar surface of the left hindpaw to establish the model of incisional pain in anesthetized rats.In group D+ R+ I, dexmedetomidine 50 μg/kg was injected subcutaneously at 30 min before establishment of the model.In R+ I and D+ R+ I groups, remifentanil was infused for 90 min at a rate of 1.2 μg·kg-1·min-1 at the same time as the model was established.In group C, normal saline was infused for 90 min at a rate of 0.12 ml·kg-1·min-1.The thermal paw withdrawal latency(TWL)and mechanical paw withdrawal threshold(MWT)were measured before administration of dexmedetomidine(T0), and at 2, 6, 24 and 48 h after stopping infusion of remifentanil(T1-4). The rats were sacrificed after the last behavioral testing, and the L4-6 segments of the spinal cord were removed for determination of the expression of NMDA receptor NR1, NR2A and NR2B subunits in membrane(m)and total(t)proteins in the spinal dorsal horn by Western blot analysis.The ratios of mNR1/tNR1, mNR2A/tNR2A and mNR2B/tNR2B were calculated. Results Compared with group C, the TWL was significantly shortened, the MWT was significantly decreased, the expression of mNR1, tNR1, mNR2B and tNR2B was significantly up-regulated, the ratios of mNR1/tNR1 and mNR2B/tNR2B were significantly increased(P 0.05). Compared with group R+ I, the TWL was significantly prolonged, the MWT was significantly increased, the expression of mNR1, tNR1, mNR2B and tNR2B was significantly down-regulated, the ratios of mNR1/tNR1 and mNR2B/tNR2B were significantly decreased(P 0.05). Conclusion The mechanism by which dexmedetomidine prevents remifentanil-induced hyperalgesia is related to reduction of trafficking of NR1 and NR2B subunits-containing NMDA receptors in spinal dorsal horn neurons of the rats with incisional pain. Key words: Dexmedetomidine; Piperidines; Receptors, N-methyl-D-aspartate; Pain; Postoperative complications; Hyperalgesia; Spinal cord