Early Systemic Granulocyte-Colony Stimulating Factor Treatment Attenuates Neuropathic Pain after Peripheral Nerve Injury 英文参考文献.docVIP

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Early Systemic Granulocyte-Colony Stimulating Factor Treatment Attenuates Neuropathic Pain after Peripheral Nerve Injury 英文参考文献.doc

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Early Systemic Granulocyte-Colony Stimulating Factor Treatment Attenuates Neuropathic Pain after Peripheral Nerve Injury 英文参考文献

EarlySystemicGranulocyte-ColonyStimulatingFactor TreatmentAttenuatesNeuropathicPainafterPeripheral NerveInjury Po-KuanChao1.,Kwok-TungLu1.,Yun-LinLee2,Jin-ChungChen3,Hung-LiWang4,Yi-LingYang5 ,Mei- YunCheng2,Ming-FengLiao2,Long-SunRo2* 1DepartmentofLifeScience,NationalTaiwanNormalUniversity,Taipei,Taiwan,2DivisionofNeuromuscularDisorders,DepartmentofNeurology,ChangGungMemorial Hospital and University, Chang-Gung University, Tao-Yuan, Taiwan, 3Department of Pharmacology, Chang-Gung University, Tao-Yuan, Taiwan, 4Department of Physiology,Chang-GungUniversity,Tao-Yuan,Taiwan,5InstituteofBiotechnology,NationalChia-YiUniversity,Chia-Yi,Taiwan Abstract Recentstudieshaveshownthatopioidtreatmentcanreducepro-inflammatorycytokineproductionandcounteractvarious neuropathic pain syndromes. Granulocyte colony-stimulating factor (G-CSF) can promote immune cell differentiation by increasingleukocytes(mainlyopioid-containingpolymorphonuclear(PMN)cells),suggestingapotentialbeneficialrolein treatingchronicpain.ThisstudyshowstheeffectivenessofexogenousG-CSFtreatment(200mg/kg)foralleviatingthermal hyperalgesia and mechanical allodynia in rats with chronic constriction injury (CCI), during post-operative days 1–25, comparedtothatofvehicletreatment.G-CSFalsoincreasestherecruitmentofopioid-containingPMNcellsintotheinjured nerve.AfterCCI,singleadministrationofG-CSFondays0,1,and2,butnotonday3,relievedthermalhyperalgesia,which indicatedthatitseffectonneuropathicpainhadatherapeuticwindowof0–48hafternerveinjury.CCIledtoanincreasein thelevelsofinterleukin-6(IL-6)mRNAandtumornecrosisfactor-a(TNF-a)proteininthedorsalrootganglia(DRG).These highlevelsofIL-6mRNAandTNF-aweresuppressedbyasingleadministrationofG-CSF48–144hand72–144hafterCCI, respectively.Furthermore,G-CSFadministered72–144hafterCCIsuppressedtheCCI-inducedupregulationofmicroglial activationintheipsilateralspinaldorsalhorn,whichisessentialforsensingneuropathicpain.Moreover,theopioidreceptor antagonistnaloxonemethiodide(NLXM)reversedG-CS