Sensory and sympathetic nerve fibers undergo sprouting and neuroma formation in the painful arthritic joint of geriatric mice 英文参考文献.docVIP

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Sensory and sympathetic nerve fibers undergo sprouting and neuroma formation in the painful arthritic joint of geriatric mice 英文参考文献.doc

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Sensory and sympathetic nerve fibers undergo sprouting and neuroma formation in the painful arthritic joint of geriatric mice 英文参考文献

Jimenez-AndradeandMantyhArthritisResearchTherapy2012,14:R101 /content/14/3/R101 RESEARCH ARTICLE OpenAccess Sensoryandsympatheticnervefibersundergo sproutingandneuromaformationinthepainful arthriticjointofgeriatricmice JuanMJimenez-Andrade1,2 andPatrickWMantyh1,3,4* Abstract Introduction:Althoughtheprevalenceofarthritisdramaticallyincreaseswithage,thegreatmajorityofpreclinical studiesconcerningthemechanismsthatdrivearthriticjointpainhavebeenperformedinyounganimals.One mechanismhypothesizedtocontributetoarthriticpainisectopicnervesprouting;however,neuroplasticityis generallythoughttobegreaterinyoungversusoldnerves.Hereweexplorewhethersensoryandsympathetic nervefiberscanundergoasignificantectopicnerveremodelinginthepainfularthritickneejointofgeriatricmice. Methods:Vehicle(saline)orcompleteFreund’sadjuvant(CFA)wasinjectedintothekneejointof27-to29- month-oldfemalemice.Painbehaviors,macrophageinfiltration,neovascularization,andthesproutingofsensory andsympatheticnervefiberswerethenassessed28dayslater,whensignificantknee-jointpainwaspresent.Knee jointswereprocessedforimmunohistochemistrybyusingantibodiesraisedagainstCD68(monocytes/ macrophages),PECAM(endothelialcells),calcitoningene-relatedpeptide(CGRP;sensorynervefibers), neurofilament200kDa(NF200;sensorynervefibers),tyrosinehydroxylase(TH;sympatheticnervefibers),and growth-associatedprotein43(GAP43;nervefibersundergoingsprouting). Results:At4weeksafterinitialinjection,CFA-injectedmicedisplayedrobustpain-relatedbehaviors(which includedflinching,guarding,impairedlimbuse,andreducedweightbearing),whereasanimalsinjectedwith vehiclealonedisplayednosignificantpain-relatedbehaviors.Similarly,intheCFA-injectedkneejoint,butnotin thevehicle-injectedkneejoint,aremarkableincreasewasnotedinthenumberofCD68+ macrophages,densityof PECAM+ bloodvessels,anddensityandformationofneuroma-likestructuresbyCGRP+,NF200+,andTH+ nerve fibersinthesynoviumandperiosteum. Conclusions:Sensoryandsympatheticnervefibersthatinnervatetheaged