The Antinociceptive Effect of Sympathetic Block is Mediated by Transforming Growth Factor β in a Mouse Model of Radiculopathy  

作　　者：Debora Denardin Luckemeyer Wenrui Xie Arthur Silveira Prudente Katherine A.Qualls Raquel Tonello Judith A.Strong Temugin Berta Jun-Ming Zhang 

机构地区：[1]Pain Research Center,Department of Anesthesiology,University of Cincinnati College of Medicine,Cincinnati,OH,45267,USA [2]Department of Molecular Pathobiology,Department of Neuroscience and Physiology,Neuroscience Institute,New York University,New York,NY,10010,USA

出　　处：《Neuroscience Bulletin》2023年第9期1363-1374,共12页神经科学通报（英文版）

基　　金：This work was supported by NIH Grants NS045594 and NS113243.

摘　　要：Although sympathetic blockade is clinically used to treat pain,the underlying mechanisms remain unclear.We developed a localized microsympathectomy(mSYMPX),by cutting the grey rami entering the spinal nerves near the rodent lumbar dorsal root ganglia(DRG).In a chemotherapy-induced peripheral neuropathy model,mSYMPX attenuated pain behaviors via DRG macrophages and the anti-inflammatory actions of transforming growth factor-β(TGF-β)and its receptor TGF-βR1.Here,we examined the role of TGF-βin sympathetic-mediated radiculopathy produced by local inflammation of the DRG(LID).Mice showed mechanical hypersensitivity and transcriptional and protein upregulation of TGF-β1 and TGF-βR1 three days after LID.Microsympathectomy prevented mechanical hypersensitivity and further upregulated Tgfb1 and Tgfbr1.Intrathecal delivery of TGF-β1 rapidly relieved the LID-induced mechanical hypersensitivity,and TGF-βR1 antagonists rapidly unmasked the mechanical hypersensitivity after LID+mSYMPX.In situ hybridization showed that Tgfb1 was largely expressed in DRG macrophages,and Tgfbr1 in neurons.We suggest that TGF-βsignaling is a general underlying mechanism of local sympathetic blockade.

关 键 词：TGF-Β SYMPATHETIC Radiculopathy:Inflammation CYTOKINE 

分 类 号：R749.3[医药卫生—神经病学与精神病学]