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Evidence for a Role of Endocannabinoids, Astrocytes and p38 Phosphorylation in the Resolution of Postoperative Pain 英文参考文献.docVIP

Evidence for a Role of Endocannabinoids, Astrocytes and p38 Phosphorylation in the Resolution of Postoperative Pain 英文参考文献.doc

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Evidence for a Role of Endocannabinoids, Astrocytes and p38 Phosphorylation in the Resolution of Postoperative Pain 英文参考文献

EvidenceforaRoleofEndocannabinoids,Astrocytesand p38PhosphorylationintheResolutionofPostoperative Pain MatthewS.Alkaitis1,2,CarlosSolorzano3,RussellP.Landry1,4,DanielePiomelli3,JoyceA.DeLeo1,4,5, E.AlfonsoRomero-Sandoval1,4,5 * 1Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, New Hampshire, United States of America, 2Nuffield Department of Clinical Laboratory Sciences,UniversityofOxford,Oxford,UnitedKingdom,3DepartmentsofPharmacologyandBiologicalChemistry,UniversityofCaliforniaIrvine,Irvine,California,United StatesofAmerica,4DepartmentofAnesthesiology,DartmouthMedicalSchool,Lebanon,NewHampshire,UnitedStatesofAmerica,5DepartmentofPharmacologyand Toxicology,DartmouthMedicalSchool,Lebanon,NewHampshire,UnitedStatesofAmerica Abstract Background: An alarming portion of patients develop persistent or chronic pain following surgical procedures, but the mechanismsunderlyingthetransitionfromacutetochronicpainstatesarenotfullyunderstood.Ingeneral,endocannabinoids (ECBs)inhibitnociceptiveprocessingbystimulatingcannabinoidreceptorstype1(CB1)andtype2(CB2).Wehavepreviously shown that intrathecal administration of a CB2 receptor agonist reverses both surgical incision-induced behavioral hypersensitivity and associated over-expression of spinal glial markers. We therefore hypothesized that endocannabinoid signalingpromotestheresolutionofacutepostoperativepainbymodulatingpro-inflammatorysignalinginspinalcordglialcells. Methodology/PrincipalFindings: Totestthishypothesis,ratsreceivingpawincisionsurgerywereusedasamodelofacute postoperativepainthatspontaneouslyresolves.WefirstcharacterizedtheconcentrationofECBsandlocalizationofCB1and CB2 receptors in the spinal cord following paw incision. We then administered concomitant CB1 and CB2 receptor 21 antagonists/inverse agonists (AM281 and AM630, 1 mg.kg each, i.p.) during the acute phase of paw incision-induced mechanicalallodyniaandevaluatedtheexpressionofglialcellmarkersandphosphorylatedp38(aMAPKassociatedwith infl

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