内源性大麻素系统与疼痛

##邸春霞*王智明李云庆(銶琚脑研究中心,西安710032)内源性大麻素系统在痛信号传递中发挥着极其重要的作用有两种类型的大麻素受体介导了此过程大麻是一种非阿片类痛觉调制物质,全身性使用大麻在各种疼痛动物模型均导致抗伤害和抗痛觉过敏的作用,并且在外周脊髓脑内均有镇痛作用内源性大麻素样物质;大麻素受体;疼痛-CB1(Cannabinoidreceptor1)CB2(Cannabinoidrecep-tor2),,80,20,,,,,,$9-($9-te-trahydrocannabino,l$9-THC),,,,[1],,1.CB1CB11990G,(adenylatecy-clase,AC)(m-itogen-activatedproteinkinase,MAPK)[2,3]CB1G,AK+,K+,DK+NP/QCa2+[3,4],CB1ACADK+,(AA)5-(5-HT)CB1/,CB1,CA1,MK+[5]CB1(CNS),(PNS)PNSCNSCB1,CNS,CB1,,[1,2]CB1,[6],CB1,CB1(PAG)(RVM)GABA(Glu)CB1,*2001#179#ChineseJournalofPainMedicine2005,11,(3)[7]2.CB2CB2CB21993G,MAPKAC[2,3]CB2CB2CB2SR144528,(palmitylethanolamide)CB2,CB2CB2CB2,,,Cb2CB2BG,CB2,[8],,CB2,,,,,,:,$9-THC;,CP55940;Aminoa-lkylindole,WIN55212,Anandamide,HU210CB2CB2HU308Palmitylethanolamine1.$9-THC$9-THC,,(-)-$9-THC$9-THCCB1CB2,(-)-$9-THCCB1CB2[9],$9-THC$9-THC,RVM,[10,11],$9-THCO-1057,$9-THC,,,O-1057[10],$9-THC,2.CP55940CP55940,(-)-,(+)-(CP56667)CP55940CB1CB2[10]CP55940PAG,[11]3.WIN55212WIN55212/(+)-[10]CB1CB2,(+)-WIN55212CB2WIN55212,[11]WIN55212-2,,WIN55212[12,13]4.AnandamideAnandamide,,AnandamideCB1CB2[10]Anandamide,,(VR1),Methanan-damideAnandamide,Methanan-#180#ChineseJournalofPainMedicine2005,11,(3)damide;MethanandamideCB1;Methanan-damide,CB1[14]Methanandamide2(COX-2)2(PGE-2),[15]Anandamide,[11]Anandamide(FAAH)FAAH,Anandamine,FAAH[16],AnandamideCB1[17]SR141716ASR144528,,1.SR141716ASR141716A,CB1,[10],cAMP[18]SR141716ASR141716ACP55940,$9-THC$8-THCHU210,Anandamide,SR141716AImproganCB1,[19]CB1,,SR141716A[20],SR141716AAnandamideMe-tF-AEA(2-methy-larach-idony-l2-'fluoro-ethylamide)[21],SR141716A()2.SR144528SR144528CB2CB2,CB2,SR144528HU210;,SR144528HU308,PalmitylethanolamideWIN55212SR144528SR141716A,SR141716A,SR144528,[22],,,,,?,:(1),CB1CB1,CB2CB2,CB1CNS,PNSCB1(2),AM381AM404AM381(stearylsulphonylfluoride)AM404[N-(4-hydroxyphenyl)arachnid-noylamide],AM381AM404,,(3),,,,,,#181#ChineseJournalofPainMedicine2005,11,(3)1FoxA,KesinglandA,GentryC,eta.lTheroleofcentralandperipheralCannabinoid1receptorsintheantihyperalgesicactivityofcannabinoidsinamodelneuropathicpain.Pain,2001,92:91~100.2PertweeRG.PharmacologyofcannabinoidCB1andCB2receptors.PharmacolTher,1997,74B129~180.3MuJ,ZhuangSY,KirbyMT,eta.lCannabinoidreceptorsdifferentiallymodulatepotassiumAandDcurrentsinhippocampalneuronsinculture.JPharmacolExpTher,1999,291B893~902.4HajosN,LedentC,FreundTF.Novelcannab-inoid-sensitivereceptormediatesinhibitionofgluta-matergicsynaptictransmissioninthehippocam-pus.Neuroscience,2001,106B1~4.5SchweitzerP.CannabinoidsdecreasetheK+M-currentinhippocampalCA1neurons.JNeurosc,i2000,20B51~58.6OngWY,MackieK.Alightandelectronmicro-scopicstudyoftheCB1cannabinoidreceptorinprimatebrain.Neuroscience,1999,92B1177~1191.7VaughanCW,McGregorIS,ChristieMJ.Cannab-inoidreceptoractivationinhibitsGABAergicneuro-transmissioninrostralventromedialmedullaneu-ronsinvitro.BrJPharmaco,l1999,127B935~940.8JordaMA,RaymanN,ValkP,eta.lIdentifica-tion,characterization,andfunctionofanovelon-cogene:theperipheralcannabinoidreceptorCb2.AnnNYAcadSc,i2003,996B10~16.9PertweeRG.Pharmacologyofcannabinoidreceptorligands.CurrMedChem,1999,6B635~664.10PertweeRG,GibsonTM,StevensonLA,eta.lO-1057,apotentwater-solublecannabinoidre-ceptoragonistwithantinociceptiveproperties.BrJPharmaco,l2000,129B1577~1584.11PertweeRG.Cannabinoidreceptorsandpain.ProgNeurobio,l2001,63B569~611.12KehlLJ,HamamotoDT,WacnikPW,eta.lAcannabinoidagonistdifferentiallyattenuatesdeeptissuehyperalgesiainanimalmodelsofcancerandinflammatorymusclepain.Pain,2003,103B175~186.13CasanovaML,Bl‚zquezC,MartŠnez-PalacioJ,eta.lInhibitionofskintumorgrowthandangiogene-sisinvivobyactivationofcannabinoidreceptors.JClinInves,t2003,111B43~50.14ZygmuntPM,PeterssonJ,AnderssonDA,eta.lVanilloidreceptorsonsensorynervesmediatethevasodilatoractionofanandamide.Nature,1999,400B452~457.15GardnerB,ZhuLX,SharmaS,eta.lMethanan-damideincreasesCOX-2expressionandtumorgrowthinmurinelungcancer.FASEBJ,2003,17B2157~2159.16WilsonRI,NicollRA.Endocannabinoidsignalinginthebrain.Science,2002,296B678~682.17RichardsonJD,AanonsenL,HargreavesKM.Antihyperalgesiceffectsofspinalcannabinoids.EurJPharmaco,l1998,345B145~153.18MatoS,PazosA,ValdizanEM.Cannabinoidre-ceptorantagonismandinverseagonisminre-sponsetoSR141716AoncAMPproductioninhu-manandratbrain.EurJPharmaco,l2002,443B43~46.19HoughLB,NalwalkJW,StadelR,eta.lInhib-itionofimproganantinociceptionbythecannab-inoid(CB)1antagonistSR141716A:lackofob-ligatoryroleforendocannabinoidsactingatCB1receptors.JPharmacolExpTher,2002,303B314~322.20CrociT,LandiM,GalzinAM,eta.lRoleofcanna-binoidCB1receptorsandtumornecrosisfactor-a-lphainthegutandsystemicant-iinflammatoryac-tivityofSR141716(Rimonabant)inrodents.BrJPharmaco,l2003,140B115~122.21PortellaG,LaezzaC,LaccettiP,eta.lInhibito-ryeffectsofcannabinoidCB1receptorstimulationontumorgrowthandmetastaticspreading:actionsonsignalsinvolvedinangiogenesisandmetasta-sis.FASEBJ,2003,17B1771~1773.22CalignanoA,LaRanaG,GiuffridaA,eta.lControlofpaininitiationbyendogenouscannab-inoids.Nature,1998,394B277~281.#182#ChineseJournalofPainMedicine2005,11,(3)