Relationship between function of spinal NMDA receptors and delta opioid receptors in a rat model of incisional pain-remifentanil-induced hyperalgesia

Abstract

Objective To investigate the relationship between the function of spinal NMDA receptors and δ opioid receptors in a rat model of incisional pain-remifentanil-induced hyperalgesia.Methods Thirty male Sprague-Dawley rats,aged 2-3 months,weighing 260-280 g,in which intrathecal catheters were successfully implanted or in which the catheter was successfully placed via the caudal vein,were randomly divided into 3 groups (n =10 each) uisng a random number table:control gourp (group C),remifentanil + incisional pain group (group RI),and δ opioid receptor inhibitor naltrindole group (group NI).A 1-cm longitudinal incision was made through skin,fascia and muscle of the plantar aspect of the hindpaw in chloral hydrate-anesthetized rats.In group C,normal saline 0.1 ml· kg-1 · min-1 was infused via the caudal vein for 60 min.In group RI,remifentanil 1.0 μg· kg-1 · min-1 was infused via the caudal vein for 60 min,and the model of incisional pain was established immediately at the beginning of infusion.In group NI,naltrindole 30 nmol (10 μl) was administrated intrathecally,then remifentanil was infused for 60 min at a rate of 1.0 μg· kg-1 · min-1 and the model of incisional pain was established immediately at the beginning of infusion.At 24 h before normal saline or remifentanil infusion and 2,6,24 and 48 h after the end of infusion (T0-4),mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured.The rats were sacrificed after the last behavioral test.L4-6 segments of the spinal cords were removed for determination of NMDA receptor expression in total and membrane protein using Western blot analysis.The ratio of NMDA receptor expression in membrane protein to that in total protein (m/t ratio) was calculated.Results Compared with the basline value at T0,MWT was significantly decreased,and TWL was shortened at T1-4 in RI and NI groups.MWT was gradualy decreased,and TWL was gradualy shortened at T1-3 and no significant difference was found between MWT and TWL at T3 and T4 in RI and NI groups.Compared with group C,MWT was significantly decreased,and TWL was shortened at T1-4,the expression of NR1-and NR2B-containing NMDA receptors in total and membrane protein was down-regulated,and m/t ratio was decreased in group NI.Conclusion Activation of δ opioid receptors can enhance the function of NR1-and NR2B-containing NMDA receptors,which may be involved in the development of incisional pain-remifentanil-induced hyperalgesia in rats. Key words: Piperidines; Hyperalgesia; Receptors, opioid, delta; Receptors, N-methyl-D-aspartate ; Spinal cord