[1]魏斌兴,李琦哲,颜海健,等.脊髓损伤后肌痉挛发病机制及治疗的研究进展[J].医学研究与战创伤救治(原医学研究生学报),2025,38(01):91-96.[doi:10.16571/j.cnki.2097-2768.2025.01.015]
　WEI Binxing,LI Qizhe,YAN Haijian,et al.Advances in pathogenesis and management of muscle spasticity following spinal cord injury[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2025,38(01):91-96.[doi:10.16571/j.cnki.2097-2768.2025.01.015]
点击复制

脊髓损伤后肌痉挛发病机制及治疗的研究进展()

《医学研究与战创伤救治》（原医学研究生学报）[ISSN:1672-271X/CN:32-1713/R]

卷:
第38卷
期数:
2025年01
页码:
91-96
栏目:
综述
出版日期:
2025-04-30

文章信息/Info

Title:
Advances in pathogenesis and management of muscle spasticity following spinal cord injury
文章编号:
2097-2768（2025）01-0091-06
作者:
魏斌兴; 李琦哲; 颜海健; 李青
作者单位：550004贵阳，贵州医科大学附属医院急诊医学科（魏斌兴、李琦哲、颜海健、李青）
Author(s):
WEI Binxing; LI Qizhe ; YAN Haijian; LI Qing
（Department of Emergency Medicine，Affiliated Hospital of Guizhou Medical University，Guiyang 550004，Guizhou，China）
关键词:
脊髓损伤; 肌痉挛; 细胞移植; γ-氨基丁酸
Keywords:
spinal cord injury; spasticity; cell transplantation; gamma-aminobutyric acid
分类号:
R681
DOI:
10.16571/j.cnki.2097-2768.2025.01.015
文献标志码:
A
摘要:
脊髓损伤（SCI）常引发肌痉挛这一长期后遗症，其表现为肌张力异常增高和随意运动的严重障碍，这些症状通常伴随患者一生。肌痉挛的发生与突触抑制的减弱和脊髓反射的过度兴奋密切相关。SCI后某些关键蛋白的下调，这些蛋白的靶向治疗已被证实可有效缓解肌痉挛症状。最近，细胞移植已成为治疗SCI后肌痉挛的研究热点之一。该方法通过重建突触抑制回路和增强神经抑制作用，有助于降低运动神经元的兴奋性，从而减轻痉挛。目前，SCI后肌痉挛的治疗方法仍然有限，为了更好地理解SCI后肌痉挛的具体发病机制，文章就SCI后肌痉挛的发生、发展及治疗前景进行综述。
Abstract:
Spinal cord injury（SCI）often leads to a long-term sequelae，namely muscle spasticity，which is characterized byabnormally high muscle tone and severe impairment of voluntary movement，and these symptoms are usually lifelong. The occurrence ofmuscle spasm is closely related to the reduction of synaptic inhibition and the overexcitation of spinal reflex. The downregulation of cer?tain key proteins after SCI，and targeted therapy of these proteins has been proven to be effective in alleviating muscle spasticity symp?toms. Recently，cell transplantation has become one of the research hotspots in the treatment of muscle spasm after SCI. This approachhelps to reduce the excitability of motor neurons by reconstructing synaptic inhibition circuits and enhancing neural inhibition，therebyalleviating spasticity. At present，the management of post-SCI muscle spasticity is still limited. In order to better understand the specif?ic pathogenesis of post-SCI muscle spasticity，this article reviews the occurrence，development and management prospects of post-SCImuscle spasticity.

参考文献/References:

［1］ Kerzonkuf M，Verneuil J，Brocard C，et al.Knockdown of cal?pain1 in lumbar motoneurons reduces spasticity after spinalcord injury in adult rats［J］.Mol Ther，2024，32（4）:1096-1109.［2］ Mahrous A，Birch D，Heckman CJ，et al.Muscle Spasms afterSpinal Cord Injury Stem from Changes in Motoneuron Excitabili?ty and Synaptic Inhibition，Not Synaptic Excitation［J］.J Neuro?sci，2024，44（1）:e1695232023.［3］ Pressey JC，de Saint-Rome M，Raveendran VA，et al.Chloridetransporters controlling neuronal excitability［J］. Physiol Rev，2023，103（2）:1095-1135.［4］ Talifu Z，Pan Y，Gong H，et al.The role of KCC2 and NKCC1 inspinal cord injury:From physiology to pathology［J］.Front Physi?ol，2022，13:1045520.［5］ Kahle KT，Khanna A，Clapham DE，et al.Therapeutic restorationof spinal inhibition via druggable enhancement of potassiumchloridecotransporter KCC2-mediated chloride extrusion in pe?ripheral neuropathic pain［J］.JAMA Neurol，2014，71（5）:640-645.［6］ Bilchak JN，Yeakle K，Caron G，et al.Enhancing KCC2 activitydecreases hyperreflexia and spasticity after chronic spinal cordinjury［J］.Exp Neurol，2021，338:113605.［7］ Penn RD，Kroin JS.Continuous intrathecal baclofen for severespasticity［J］.Lancet，1985，2（8447）:125-127.［8］ Dietz N，Wagers S，Harkema SJ，et al.Intrathecal and Oral Ba?clofen Use in Adults With Spinal Cord Injury:A Systematic Re?view of Efficacy in Spasticity Reduction，Functional Changes，Dosing，and Adverse Events［J］.Arch Phys Med Rehabil，2023，104（1）:119-131.［9］ Palazón-García R，Benavente-Valdepe?as AM.Botulinum Toxin:From Poison to Possible Treatment for Spasticity in Spinal CordInjury［J］.Int J Mol Sci，2021，22（9）:4886.［10］ Fang CY，Lien ASY，Tsai JL，et al. The Effect and Dose-Re?sponse of Functional Electrical Stimulation Cycling Training onSpasticity in Individuals With Spinal Cord Injury:A SystematicReview With Meta-Analysis［J］.Front Physiol，2021，12:756200.［11］ Hurth H，Morgalla M，Heinzel J，et al.Surgical procedures fortreatment of spasticity［J］.Nervenarzt，2023，94（12）:1116-1122.［12］ Gong C，Zheng X，Guo F，et al.Human spinal GABA neurons al?leviate spasticity and improve locomotion in rats with spinalcord injury［J］.Cell Rep，2021，34（12）:108889.［13］ 卫波，李建军.脊髓损伤后肌痉挛机制与治疗［J］.中国康复理论与实践，2006，12（7）:559-562.［14］ Ji B，Wojta? B，Skup M.Molecular Identification of Pro-Excito?genic Receptor and Channel Phenotypes of the DeafferentedLumbar Motoneurons in the Early Phase after SCT in Rats［J］.Int J Mol Sci，2022，23（19）:11133.［15］ Yu W，Sohn JW，Kwon J，et al.Enhancement of dendritic persis?tent Na+ currents by mGluR5 leads to an advancement of spiketiming with an increase in temporal precision［J］. Mol Brain，2018，11（1）:67.［16］ Jiang MC，Birch DV，Heckman CJ，et al. The Involvement ofCaV1.3 Channels in Prolonged Root Reflexes and Its Potentialas a Therapeutic Target in Spinal Cord Injury［J］.Front NeuralCircuits，2021，15:642111.［17］ Norton JA，Bennett DJ，Knash ME，et al.Changes in sensoryevokedsynaptic activation of motoneurons after spinal cord inju?ry in man［J］.Brain，2008，131（Pt 6）:1478-1491.［18］ Bellardita C，Caggiano V，Leiras R，et al.Spatiotemporal correla?tion of spinal network dynamics underlying spasms in chronicspinalized mice［J］.Elife，2017，6:e23011.［19］ Thaweerattanasinp T，Birch D，Jiang MC，et al.Bursting interneu?rons in the deep dorsal horn develop increased excitability andsensitivity to serotonin after chronic spinal injury［J］.J Neuro?physiol，2020，123（5）:1657-1670.［20］ Lin S，Li Y，Lucas-Osma AM，et al.Locomotor-related V3 inter?neurons initiate and coordinate muscles spasms after spinalcord injury［J］.J Neurophysiol，2019，121（4）:1352-1367.［21］ Kent CN，Park C，Lindsley CW.Classics in Chemical Neurosci?ence: Baclofen［J］. ACS Chem Neurosci，2020，11（12）: 1740-1755.［22］ Zhang S，Meor Azlan NF，Josiah SS，et al.The role of SLC12A family of cation-chloride cotransporters and drug discoverymethodologies［J］.J Pharm Anal，2023，13（12）:1471-1495.［23］ Al Awabdh S，Donneger F，Goutierre M，et al.Gephyrin Interactswith the K-Cl Cotransporter KCC2 to Regulate Its Surface Ex?pression and Function in Cortical Neurons［J］.J Neurosci，2022，42（2）:166-182.［24］ Sah R，Galeffi F，Ahrens R，et al.Modulation of the GABA（A）-gated chloride channel by reactive oxygen species［J］.J Neuro?chem，2002，80（3）:383-391.［25］ Mazzone GL，Mohammadshirazi A，Aquino JB，et al.GABAergicMechanisms Can Redress the Tilted Balance between Excitationand Inhibition in Damaged Spinal Networks［J］.Mol Neurobiol，2021，58（8）:3769-3786.［26］ Furukawa T，Fukuda A.Maternal taurine as a modulator of Clhomeostasisas well as of glycine/GABAA receptors for neocorti?cal development［J］.Front Cell Neurosci，2023，17:1221441.［27］ Lee KL，Abiraman K，Lucaj C，et al.Inhibiting with-no-lysine ki?nases enhances K+/Cl-cotransporter 2 activity and limits statusepilepticus［J］.Brain，2022，145（3）:950-963.［28］ McMoneagle E，Zhou J，Zhang S，et al.Neuronal K+-Cl- cotrans?porter KCC2 as a promising drug target for epilepsy treatment［J］.Acta Pharmacol Sin，2024，45（1）:1-22.［29］ Lee HHC，Walker JA，Williams JR，et al.Direct protein kinaseC-dependent phosphorylation regulates the cell surface stabilityand activity of the potassium chloride cotransporter KCC2［J］.JBiol Chem，2007，282（41）:29777-29784.［30］ Kfir A，Awasthi R，Ghosh S，et al. A Cellular Mechanism ofLearning-Induced Enhancement of Synaptic Inhibition:PKC-De?pendent Upregulation of KCC2 Activation［J］.Sci Rep，2020，10（1）:962.［31］ Chen M，Lin Y，Guo W，et al.BMSC-Derived Exosomes CarryingmiR-26a-5p Ameliorate Spinal Cord Injury via Negatively Regu?lating EZH2 and Activating the BDNF-TrkB-CREB Signaling［J］.Mol Neurobiol，2024，61（10）:8156-8174.［32］ Zhao S，Wang F，Wang L，et al.Involvement of the BDNF-TrkBKCC2pathway in neuropathic pain after brachial plexus avul?sion［J］.Brain Behav，2022，12（3）:e2464.［33］ Cao T，Chen H，Huang W，et al.hUC-MSC-mediated recovery ofsubacute spinal cord injury through enhancing the pivotal sub?units β3 and γ2 of the GABAA receptor［J］.Theranostics，2022，12（7）:3057-3078.［34］ Delmotte Q，Hamze M，Medina I，et al.Smoothened receptor sig?naling regulates the developmental shift of GABA polarity in ratsomatosensory cortex［J］.J Cell Sci，2020，133（20）:jcs247700.［35］ de Sousa N，Santos D，Monteiro S，et al.Role of Baclofen in Mod?ulating Spasticity and Neuroprotection in Spinal Cord Injury［J］.J Neurotrauma，2022，39（3-4）:249-258.［36］ Hilton BJ，Husch A，Schaffran B，et al.An active vesicle primingmachinery suppresses axon regeneration upon adult CNS injury［J］.Neuron，2022，110（1）:51-69.［37］ Bagues A，Hu J，Alshanqiti I，et al.Neurobiological mechanismsof botulinum neurotoxin-induced analgesia for neuropathic pain［J］.Pharmacol Ther，2024，259:108668.［38］ Rahman MA，Tharu NS，Gustin SM，et al.Trans-Spinal ElectricalStimulation Therapy for Functional Rehabilitation after SpinalCord Injury:Review［J］.J Clin Med，2022，11（6）:1550.［39］ Pereira M，Fernandes SR，Miranda PC，et al.Neuromodulation oflower limb motor responses with transcutaneous lumbar spinalcord direct current stimulation［J］.Clin Neurophysiol，2018，129（9）:1999-2009.［40］ Malloy DC，C?té MP.Multi-session transcutaneous spinal cordstimulation prevents chloride homeostasis imbalance and the de?velopment of hyperreflexia after spinal cord injury in rat［J］.ExpNeurol，2024，376:114754.［41］ 高玉玲，张丽欢，刘勇.经颅磁刺激治疗脊髓损伤痉挛的研究进展［J］.医学研究生学报，2020，33（5）:543-549.［42］ Benson CA，Olson KL，Patwa S，et al. Conditional AstrocyteRac1KO Attenuates Hyperreflexia after Spinal Cord Injury［J］.JNeurosci，2024，44（1）:e1670222023.［43］ Kauer SD，Benson CA，Carrara JM，et al.PAK1 inhibition withRomidepsin attenuates H -reflex hyperexcitability after spinalcord injury［J］.J Physiol，2024，602（19）:5061-5081.［44］ Liao YH，Chen MX，Chen SC，et al.Low-Intensity Focused Ultra?sound Alleviates Spasticity and Increases Expression of the Neu?ronal K-Cl Cotransporter in the L4-L5 Sections of Rats Follow?ing Spinal Cord Injury［J］. Front Cell Neurosci，2022，16:882127.［45］ Li X，Song X，Fang L，et al.Body Weight-Supported TreadmillTraining Ameliorates Motoneuronal Hyperexcitability by In?creasing GAD-65/67 and KCC2 Expression via TrkB Signalingin Rats with Incomplete Spinal Cord Injury［J］.Neurochem Res，2022，47（6）:1679-1691.［46］ Caron G，Bilchak J，C?té MP.Bumetanide increases postsynapticinhibition after chronic SCI and decreases presynaptic inhibi?tion with step-training［J］. J Physiol，2023，601（8）:1425-1447.［47］ Guo F，Zheng X，He Z，et al.Nimodipine Promotes FunctionalRecovery After Spinal Cord Injury in Rats［J］.Front Pharmacol，2021，12:733420.［48］ Zheng X，Zhu B，Xu J，et al.Human spinal GABA neurons sur?vive and mature in the injured nonhuman primate spinal cord［J］.Stem Cell Reports，2023，18（2）:439-448.［49］ Bhagwani A，Chopra M，Kumar H.Spinal Cord Injury ProvokedNeuropathic Pain and Spasticity，and Their GABAergic Connec?tion［J］.Neurospine，2022，19（3）:646-668.［50］ Abolghasemi R，Davoudi-Monfared E，Allahyari F，et al.System?atic Review of Cell Therapy Efficacy in Human Chronic SpinalCord Injury［J］.Tissue Eng Part B Rev，2024，30（2）:254-269.

相似文献/References:

[1]王静,陶峰琴,诸葛恒艳.护理干预模式对围手术期脊柱骨折合并脊髓损伤患者负性情绪及生活质量的应用效果[J].医学研究与战创伤救治(原医学研究生学报),2023,25(3):315.[doi:10.3969/j.issn.1672-271X.2023.03.019]

备注/Memo

备注/Memo:
基金项目：国家自然科学基金（82160249）
更新日期/Last Update: 2025-01-20