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mTOR信号通路在神经病理疼痛大鼠脊髓背角突触可塑性的作用的任务书.docx

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mTOR信号通路在神经病理疼痛大鼠脊髓背角突触可塑性的作用的任务书 Introduction: Chronicneuropathicpainisoneofthecommonproblemsthatcanoccurasaresultofnervedamage,diseases,orinjuries.Theconditionischaracterizedbychronicpainthatpersistsbeyondthehealingofdamagedtissues,anditoftenaffectsthequalityoflifeforpatients.Centralsensitizationplaysapivotalroleinneuropathicpain,anditinvolvesalteredsynapticplasticityinthedorsalhornofthespinalcord.Themammaliantargetofrapamycin(mTOR)signalingpathwayhasemergedasacriticalregulatorofsynapticplasticityandhasbeenshowntobeinvolvedinthedevelopmentofchronicpain.ThepresentstudyaimstoinvestigatetheroleofthemTORsignalingpathwayinthesynapticplasticityofthedorsalhornofthespinalcordinaratmodelofneuropathicpain. Methods: Atotalof40ratswillbedividedintofourgroups:acontrolgroup,ashamgroup,anerveinjurygroup,andarapamycintreatmentgroup.Theneuropathicpainmodelwillbeestablishedbychronicconstrictioninjuryofthesciaticnerve.TheratsintherapamycintreatmentgroupwillreceiveanintrathecalinjectionofrapamycintoinhibitthemTORsignalingpathway.Thecontrolandshamgroupswillreceivesalineinjections.Thenociceptivebehavioroftheratswillbeassessedusingthepawwithdrawalthresholdandpawwithdrawallatencytests.Thesynapticplasticityofthedorsalhornofthespinalcordwillbeexaminedusingelectrophysiologicaltechniques,includingfieldpotentialrecordingandwhole-cellpatch-clamprecording. ExpectedResults: Weexpectthatchronicconstrictioninjuryofthesciaticnervewillresultinthedevelopmentofneuropathicpaininrats,asevidencedbyadecreaseinthepawwithdrawalthresholdandanincreaseinthepawwithdrawallatency.WealsoexpectthatthemTORsignalingpathwaywillbeactivatedinthedorsalhornofthespinalcordofthenerveinjurygroup.TheactivationofthemTORpathwaywillleadtoanincreaseinthesynapticplasticityofthedorsalhornofthespinalcord,asindicatedbyanincreaseintheamplitudeoffieldpotentialsandanincreaseinthefrequencyofminiatureexcitatorypostsynapticcurrents(mEPSCs).TheinhibitionofthemTORpathwayintherapamycintreatmentgroupisexpectedtoreducethesynapticplasticityofthe