Switching From Morphine To Fentanyl Attenuated The Decline Of μ,δOpioid Receptor And β-arrestin2 Expression In Periaqueductal Gray Of Rats

Objective Opioid switching is a therapeutic maneuver as a method of improving analgesic response and/or reducing adverse side effects. Theμ-opioid receptor (MOR) has important role in mediating the actions of morphine and other analgesic agents, which is mediated by theδ-opioid receptor (DOR) andβ-arrestin2. This study is aimed to explore the changes of MOR,DOR andβ-arrestin2 in the periaqueductal gray (PAG) in rats when morphine is substituted with equianalgesic fentanyl.Methods With approval of Institution of Laboratory Animal Science of Peking Union Medical College,40 rats were randomly assigned equally to five treatment groups, which are 7 days normal saline group (N group),7 days fentanyl group (F group),7 days morphine group (M group),14 days morphine-fentanyl-switching group (MF group),14 days morphine group (MM group), and repeatedly received subcutaneous (s.c.) injection of morphine sulfate (10 mg/kg) or equianalgesic fentanyl sulfate(0.1 mg/kg). Pain threshold in rats was measured using hot water tail-flick latency (TFL). MOR,DOR andβ-arrestin2 mRNA and protein expression in PAG were measured using RT-PCR and Western blot analyses respectively.Results Our results showed that equianalgesic fentanyl was still antinociceptive effective to rats with morphine tolerance. We also demonstrated that both MOR,DOR andβ-arrestin2 mRNA and protein expression in PAG of rats in MF group were less than that in M group (P< 0.05) but more than that in MM group (P< 0.05).Conclusion Our data suggest that antinociceptive effectiveness of fentanyl to rats with morphine tolerance is likely to be caused by the fact that fentanyl, as a high efficacy opioid, has lower fractional receptor occupancy and mild tendency to decrease MOR DOR andβ-arrestin2 mRNA and protein expression in PAG than low efficacy morphine.