Selective Targeting of TRPV1 Expressing Sensory Nerve Terminals in the Spinal Cord for Long Lasting Analgesia 英文参考文献.docVIP

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Selective Targeting of TRPV1 Expressing Sensory Nerve Terminals in the Spinal Cord for Long Lasting Analgesia 英文参考文献.doc

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SelectiveTargetingofTRPV1ExpressingSensoryNerve TerminalsintheSpinalCordforLongLastingAnalgesia JosephA.Jeffry1.,Shuang-QuanYu1.,ParulSikand1,ArtiParihar1,M.StevenEvans2, LouisS.Premkumar1* 1DepartmentofPharmacology,SouthernIllinoisUniversitySchoolofMedicine,Springfield,Illinois,UnitedStatesofAmerica,2DepartmentofNeurology,SouthernIllinois UniversitySchoolofMedicine,Springfield,Illinois,UnitedStatesofAmerica Abstract Chronic pain is a major clinical problem and opiates are often the only treatment, but they cause significant problems ranging from sedation to deadly respiratory depression. Resiniferatoxin (RTX), a potent agonist of Transient Receptor PotentialVanilloid1(TRPV1),causesaslow,sustainedandirreversibleactivationofTRPV1andincreasesthefrequencyof spontaneous excitatory postsynaptic currents, but causes significant depression of evoked EPSCs due to nerve terminal depolarizationblock.IntrathecaladministrationofRTXtoratsintheshort-terminhibitsnociceptivesynaptictransmission, andinthelong-termcausesalocalized,selectiveablationofTRPV1-expressingcentralsensorynerveterminalsleadingto long lasting analgesia in behavioral models. Since RTX actions are selective for central sensory nerve terminals, other efferentfunctionsofdorsalrootganglionneuronscanbepreserved.Preventingnociceptivetransmissionatthelevelofthe spinalcordcanbeausefulstrategytotreatchronic,debilitatingandintractablepain. Citation:JeffryJA,YuS-Q,SikandP,PariharA,EvansMS,etal.(2009)SelectiveTargetingofTRPV1ExpressingSensoryNerveTerminalsintheSpinalCordfor LongLastingAnalgesia.PLoSONE4(9):e7021.doi:10.1371/journal.pone.0007021 Editor:HiroakiMatsunami,DukeUnviersity,UnitedStatesofAmerica ReceivedJune8,2009;AcceptedAugust10,2009;PublishedSeptember15,2009 Copyright: ? 2009 Jeffry et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Fun