Switching from morphine to fentanyl attenuates the decline of μ-opioid receptor expression in periaqueductal gray of rats with morphine tolerance.pdfVIP

Switching from morphine to fentanyl attenuates the decline of μ-opioid receptor expression in periaqueductal gray of rats with morphine tolerance.pdf

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Switching from morphine to fentanyl attenuates the decline of μ-opioid receptor expression in periaqueductal gray of rats with morphine tolerance

3712 ChinMedJ2013,126fl91 Originalarticle Switchingfrom morphinetofentanylattenuatesthedeclineofp--opioid receptorexpressioninperiaqueductalgrayofratswithmorphine tolerance DONGYan-peng,SUN Li,LIU Xiao—yanandLIU Ruo-shan Keywords:morphine,[entanyl,tolerance,switching;p—opioidreceptor,periaqueductalgray BackgroundOpioidswitching isatherapeuticmaneuverto improveanalgesicresponseand/orreduceadverseside effectsalthoughtheunderlyingmechanismsremainunknown.Thep-opioidreceptor(MOR)hasanimportantrolein mediatingtheactionsofmorphineandotheranalgesicagents.ThisstudyisaimedatexploringthechangesofMORinthe periaqueductalgray(PAG)inratswhenmorphineissubstitutedforequianalgesicfentany1. MethodsForlyratswererandomlyassignedtofivetreatmentgroups:7daysnormalsalinegroup(Ngroup),7daysfentanyl group(Fgroup),7daysmorphinegroup(Mgroup),7daysmorphineand7daysfentanyl—switchinggroup(MFgroup),and 14daysmorphinegroup(MM group).Ratsrepeatedlyreceivedsubcutaneousinjectionsofmorphinesulfate(10mg/kg) orequianalgesicfentanylsulfate(0.1mg/kg)twicedaily.Rats’antinociceptiveresponsetothermalpainwasevaluatedby thetaiIflickIatencyassay.MORmRNA andproteinexpressioninthePAG weremeasuredusingRT-PCR andW estern blottinganalysesrespectively. Results Thisstudyshowedthataftermorphinewassubstitutedwithfentanylonday8,thetaiIflicklatency(TFL) increasedfr0m (3.9+0.4)secondsto(11.4+0.4)seconds.TheresultsalsodemonstratedthatbothMORmRNAandprotein expressioninthePAGofratsintheMFgroupwerelessthanthatintheMgroup(P0.05)butmorethanthatinMMgroup (P0.O5). Conclusions Equianalgesicfentany1wasstilIantinOciceptiveeffectiveinratswithmorphinetolerance,whichmaybedue totheswitchingfr0m morphinetofentanyIattenuatingthedeclineofMORexpressioninthePAG ofrats. ChinMedJ20

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