Neuronal Panx1 drives peripheral sensitization in experimental plantar inflammatory pain  

作　　者：Qu Xing Antonio Cibelli Greta Luyuan Yang Preeti Dohare Qing-Hua Li Eliana Scemes Fang-Xia Guan David C.Spray 

机构地区：[1]School of Life Sciences,Zhengzhou University,Zhengzhou 450001,China [2]Dominick P.Purpura Department of Neuroscience,Albert Einstein College of Medicine,Bronx,NY 10461,USA [3]Department of Biosciences,Biotechnologies and Biopharmaceutics,University of Bari Aldo Moro,Bari 70125,Italy [4]Department of Molecular Biology and Biochemistry,Wesleyan University,Middletown,CT 06459,USA [5]Department of Neuroscience and Experimental Therapeutics,Albany Medical College,Albany,NY 12208,USA [6]Department of Anatomy and Cell Biology,New York Medical College,Valhalla,NY 10595,USA [7]Institute of Neuroscience,Zhengzhou University,Zhengzhou 450001,China

出　　处：《Military Medical Research》2025年第2期204-219,共16页军事医学研究(英文版)

基　　金：This work was NIH(R01NS092466),NSFC(U2004201);Central Plains Thousand People Plan of Henan Province(204200510013);Henan Overseas Expertise Introduction Center for Discipline Innovation(CXJD2021002);Key Special Project of Zhengzhou University Disciplinary Construction(XKZDJC202001)。

摘　　要：Background:The channel-forming protein Pannexin1(Panx1)has been implicated in both human studies and animal models of chronic pain,but the underlying mechanisms remain incompletely understood.Methods:Wild-type(WT,n=24),global Panx1 KO(n=24),neuron-specific Panx1 KO(n=20),and glia-specific Panx1 KO(n=20)mice were used in this study at Albert Einstein College of Medicine.The von Frey test was used to quantify pain sensitivity in these mice following complete Freund’s adjuvant(CFA)injection(7,14,and 21 d).The qRT-PCR was employed to measure mRNA levels of Panx1,Panx2,Panx3,Cx43,Calhm1,andβ-catenin.Laser scanning confocal microscopy imaging,Sholl analysis,and electrophysiology were utilized to evaluate the impact of Panx1 on neuronal excitability and morphology in Neuro2a and dorsal root ganglion neurons(DRGNs)in which Panx1 expression or function was manipulated.Ethidium bromide(EtBr)dye uptake assay and calcium imaging were employed to investigate the role of Panx1 in adenosine triphosphate(ATP)sensitivity.β-galactosidase(β-gal)staining was applied to determine the relative cellular expression levels of Panx1 in trigeminal ganglia(TG)and DRG of transgenic mice.Results:Global or neuron-specific Panx1 deletion markedly decreased pain thresholds after CFA stimuli(7,14,and 21 d;P<0.01 vs.WT group),indicating that Panx1 was positively correlated with pain sensitivity.In Neuro2a,global Panx1 deletion dramatically reduced neurite extension and inward currents compared to the WT group(P<0.05),revealing that Panx1 enhanced neurogenesis and excitability.Similarly,global Panx1 deletion significantly suppressed Wnt/β-catenin dependent DRG neurogenesis following 5 d of nerve growth factor(NGF)treatment(P<0.01 vs.WT group).Moreover,Panx1 channels enhanced DRG neuron response to ATP after CFA injection(P<0.01 vs.Panx1 KO group).Furthermore,ATP release increased Ca2+responses in DRGNs and satellite glial cells surrounding them following 7 d of CFA treatment(P<0.01 vs.Panx1 KO group),suggesting that Panx1 in glia also impacts

关 键 词：Pannexin1(Panx1) Dorsal root ganglion Satellite glial cell Peripheral sensitization Plantar inflammatory pain 

分 类 号：R73[医药卫生—肿瘤]