Relationship between delta opioid receptors and activity of glycogen synthase kinase-3β in spinal cord during hyperalgesia induced by remifentanil in a rat model of incisional pain / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the relationship between delta opioid receptors (DORs) and activity of glycogen synthase kinase-3β (GSK-3β) in the spinal cord during hyperalgesia induced by remifentanil in a rat model of incisional pain (IP).Methods Twenty-four male Sprague-Dawley rats,aged 240-260 g,weighing 2-3 months,were randomly divided into 3 groups (n =8 each) using a random number tablecontrol group (group C),remifentanil+IP group (group R+I) and DOR antagonist naltrindole group (group N).A 1-cm longitudinal incision was made in the plantar surface of the left hindpaw in anesthetized rats.In group C,the equal volume of normal saline was injected intraperitoneally,and normal saline was then infused for 60 min at the same rate.In group R+I,the equal volume of normal saline was injected intraperitoneally,remifentanil was infused for 60 min at 1.2 μg · kg-1 · min-1,and IP was produced immediately after onset of remifentanil infusion.In group N,naltrindole 0.1 mg/kg was injected intraperitoneally,remifentanil was infused for 60 min at 1.2 μg · kg-1 · min-1,and IP was produced immediately after onset of remifentanil infusion.At 24 h before infusion of normal saline or remifentanil and 2,6,24 and 48 h after iv administration (T0-4),the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured.The rats were sacrificed after the last measurement of pain threshold,the lumbar segment (L4-6) of the spinal cord was removed for determination of the expression of GSK-3β,phosphor-GSK-3β (pGSK-3β) (by Western blot) and GSK-3β mRNA (realtime PCR).The ratio of pGSK-3β /GSK-3β was calculated.Results Compared with group C,the MWT was significantly decreased,and the TWL was shortened at T1 4,the expression of GSK-3β,pGSK-3β and GSK-3β mRNA was up-regulated,and pGSK-3β/GSK-3β ratio was decreased in R + I and N groups.Compared with group R + I,thc MWT was significantly incrcased,and the TWL was prolonged at T1-4,the expression of GSK-3β,pGSK-3β and GSK-3β rmRNA was down-regulated,and pGSK-3β/GSK-3β ratio was increased in group N.Conclusion Activation of DOR is involved in enhancement of activity of GSK-3β in the spinal cord during hyperalgesia induced by remifentanil in a rat model of IP.