ABSTRACT
Objective To evaluate the effect of the opioid switch from morphine to sufentanil on the expression of μ-opioid receptors in the midbrain periaqueductal gray (PAG) of rats.Methods Forty healthy male Wistar rats,aged 8 weeks,weighing 250-290 g,were randomly assigned into 5 groups (n=8 each) using a random number table:control group (group C),7 day sufentanil group (group S),7 day morphine group (group M),14 day morphine group (group MM),and 14 day alternate administration of morphine and sufentanil group (group MS).Normal saline 2 ml/kg,sufentanil 0.01 mg/kg and morphine 10 mg/kg were injected subcutaneously in the cervical region twice a day for 7 consecutive days in C,S and M groups,respectively.In group MM,morphine 10 mg/kg was injected subcutaneously in the cervical region twice a day for 14 consecutive days.In group MS,morphine 10 mg/kg was injected subcutaneously in the cervical region twice a day for 7 consecutive days (1st-7th days),and sufentanil 0.01 mg/kg was then injected subcutaneously in the cervical region twice a day for 7 consecutive days (8th-14th days).The tail flick latency (TFL) to a thermal nociceptive stimulus was measured at 15 and 30 min after the initial administration every day.After the last administration,the rats were sacrificed,and the midbrain PAG was isolated for determination of the expression of the μ-opioid receptor and μ-opioid receptor mRNA using Western blot and real-time reverse transcriptase polymerase chain reaction,respectively.Results Compared with group C,the TFL was significantly prolonged on 1st-6th days after the beginning of administration in M,MM and MS groups,the TFL was significantly prolonged on 1st-7th days after the beginning of administration in group S,and the expression of the μ-opioid receptor and μ-opioid receptor mRNA in the midbrain PAG was significantly down-regulated in M,MM and MS groups (P＜0.05).Compared with group MM,the TFL was significantly prolonged on 8th-14th days after the beginning of administration,and the expression of the μ-opioid receptor and μ-opioid receptor mRNA in the midbrain PAG was significantly up-regulated in group MS (P＜0.05).Conclusion The mechanism by which the opioid switch from morphine to sufentanil reduces morphine tolerance is related to enhanced activity of μ-opioid receptors in the midbrain PAG of rats.