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Tuina alleviates neuropathic pain through regulate the activation of microglia and the secretion of inflammatory cytokine in spinal cord

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Journal of Traditional Chinese Medicine 2024年第4期44卷 762-769页

作者： WU Zhiwei ZHU Qingguang KONG Lingjun SONG Pengfei ZHOU Xin GUO Guangxin ZHANG Shuaipan HE Tianxiang CHENG Yanbin FANG Min Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Shanghai University of Traditional Chinese Medicine Institute of Tuina Shanghai Institute of Traditional Chinese Medicine Shuguang Hospital Shanghai University of Traditional Chinese Medicine Department of Acupuncture and Tuina Shanghai University of Traditional Chinese Medicine

OBJECTIVE: To observe the analgesic effects of Tuina on neuropathic pain(NPP) and the underlying mechanisms. METHODS: Forty-eight Sprague-Dawley(SD) rats were assigned by random into three treatment groups: sham, chronic constriction injury(CCI), and Tuina. Each group contained sixteen rats. CCI model was generated by ligating the right sciatic nerve. Behavioral changes of CCI were assessed by the paw withdrawal threshold(PWT) and paw withdrawal latency(PWL). In addition, biochemical techniques such as immunofluorescence staining, enzyme-linked immunosorbent assay(ELISA) and Western blotting were used to profile levels of microglia activation and inflammatory factors in the spinal dorsal horn(SDH) of rats. Tuina(clockwise pressing and rubbing) was performed at Chengshan(BL57) to observe the analgesic effects on CCI rats and the underlying mechanisms. RESULTS: Rats with CCI experienced significant reduction in the PWT and PWL of the right hind paw relative to CCI group at day 3. Tuina treatment rescued this situation significantly on days 10 and 14. Besides, Iba-1, microglia M1 receptor CD68, tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) were higher in the right SDH for CCI group compared to the sham group on day 14. As expected, Tuina partially downregulated the CCI-induced overexpressed Iba-1, CD68, TNF-α, and IL-1β in the SDH of CCI model. CONCLUSION: Tuina induces a time-dependent cumulative analgesic effect in CCI rats by inhibiting the activation of microglia and the secretion of IL-1β and TNF-α in SDH.

关键词： Tuina inflammatory cytokine microglia neuralgia spinal cord

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The functional properties of synapses made by regenerated axons across spinal cord lesion sites in lamprey

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Neural Regeneration Research 2022年第10期17卷 2272-2277页

作者： David Parker Department of Physiology Developmentand NeuroscienceUniversity of CambridgeCambridgeUK

While the anatomical properties of regenerated axons across spinal cord lesion sites have been studied extensively,little is known of how the functional properties of regenerated synapses compared to those in unlesioned *** study aims to compare the properties of synapses made by regenerated axons with unlesioned axons using the lamprey,a model system for spinal injury research,in which functional locomotor recovery after spinal cord lesions is associated with axonal regeneration across the lesion *** synapses below the lesion site did not differ from synapses from unlesioned axons with respect to the amplitude and duration of single excitatory postsynaptic *** also showed the same activity-dependent depression over spike ***,regenerated synapses did differ from unlesioned synapses as the estimated number of synaptic vesicles was greater and there was evidence for increased postsynaptic quantal *** axons above the lesion site,the amplitude and duration of single synaptic inputs also did not differ significantly from unlesioned ***,in this case,there was evidence of a reduction in release probability and inputs facilitated rather than depressed over spike *** inputs from single regenerated axons below the lesion site thus do not increase in amplitude to compensate for the reduced number of descending axons after functional ***,the postsynaptic input was maintained at the unlesioned level using different synaptic ***,the facilitation from the same initial amplitude above the lesion site made the synaptic input over spike trains functionally *** may help to increase propriospinal activity across the lesion site to compensate for the lesion-induced reduction in supraspinal *** animal experiments were approved by the Animal Ethics Committee of Cambridge University.

关键词： electrophysiology lamprey plasticity regeneration reticulospinal axon spinal cord spinal injury synapse

Gradient descent decomposition of force-field motor primitives optogenetically elicited for motor mapping of the murine lumbosacral spinal cord

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Zoological Research 2023年第3期44卷 604-619页

作者： Paola Salmas Vincent C.K Cheung School of Biomedical Sciences and Gerald Choa Neuroscience InstituteThe Chinese University of Hong KongHong Kong SARChina Kunming Institute of Zoology-The Chinese University of Hong Kong(KIZ-CUHK)Joint Laboratory of Bioresources and Molecular Research of Common Diseases Hong Kong SARChina

Generating diverse motor behaviors critical for survival is a challenge that confronts the central nervous system(CNS)of all *** movement execution,the CNS performs complex calculations to control a large number of neuromusculoskeletal *** theory of modular motor control proposes that spinal interneurons are organized in discrete modules that can be linearly combined to generate a variety of behavioral *** modules have been previously represented as stimulus-evoked force fields(FFs)comprising isometric limb-endpoint forces across workspace ***,we ask whether FFs elicited by different stimulations indeed represent the most elementary units of motor control or are themselves the combination of a limited number of even more fundamental motor *** probe for potentially more elementary modules,we optogenetically stimulated the lumbosacral spinal cord of intact and spinalized Thy1-ChR2 transgenic mice(n=21),eliciting FFs from as many single stimulation loci as possible(20-70 loci per mouse)at minimally necessary *** found that the resulting varieties of FFs defied simple categorization with just a few *** used gradient descent to further decompose the FFs into their underlying basic force fields(BFFs),whose linear combination explained FF *** mice,we identified 4-5 BFFs with partially localizable but overlapping representations along the spinal *** BFFs were structured and topographically distributed in such a way that a rostral-to-caudal traveling wave of activity across the lumbosacral spinal cord may generate a swing-to-stance gait *** BFFs may represent more rudimentary submodules that can be flexibly merged to produce a library of motor modules for building different motor behaviors.

关键词： Motor mapping Optogenetics spinal cord Motor primitives Traveling wave

Growth associated protein 43 and neurofilament immunolabeling in the transected lumbar spinal cord of lizard indicates limited axonal regeneration

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Neural Regeneration Research 2022年第5期17卷 1034-1041页

作者： Lorenzo Alibardi Comparative Histolab Padova and Department of Biology University of BolognaBolognaItaly

Previous cytological studies on the transected lumbar spinal cord of lizards have shown the presence of differentiating glial cells,few neurons and axons in the bridge region between the proximal and distal stumps of the spinal cord in some cases.A limited number of axons(20-50)can cross the bridge and re-connect the caudal stump of the spinal cord with small neurons located in the rostral stump of the spinal *** axonal regeneration appears to be related to the recovery of hind-limb movements after initial *** present study extends previous studies and shows that after transection of the lumbar spinal cord in lizards,a glial-connective tissue bridge that reconnects the rostral and caudal stumps of the interrupted spinal cord is formed at 11-34 days *** an initial paralysis some recovery of hindlimb movements occurs within 1-3 months *** and ultrastructural analysis for a growth associated protein 43(GAP-43)of 48-50 k Da shows that sparse GAP-43 positive axons are present in the proximal stump of the spinal cord but their number decreased in the bridge at 11-34 days *** immunolabeled axons with a neurofilament protein of 200-220 k Da were seen in the bridge at 11-22 days post-transection but their number increased at 34 days and 3 months post-amputation in lizards that have recovered some hindlimb *** neurons in the rostral and caudal stumps of the spinal cord were also labeled for GAP43,a cytoplasmic protein that is trans-located into their axonal growth *** indicates that GAP-43 biosynthesis is related to axonal regeneration and sprouting from neurons that were damaged by the *** together,previous studies that utilized tract-tracing technique to label the present observations confirm that a limited axonal re-connection of the transected spinal cord occurs 1-3 months post-injury in *** few regenerating-sprouting axons within the bridge reconnect

关键词： GAP-43 immunocytochemistry lizard neurofilaments regeneration spinal cord

High-intensity swimming alleviates nociception and neuroinflammation in a mouse model of chronic postischemia pain by activating the resolvin E1-chemerin receptor 23 axis in the spinal cord

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Neural Regeneration Research 2023年第11期18卷 2535-2544页

作者： Xin Jia Ziyang Li Xiafeng Shen Yu Zhang Li Zhang Ling Zhang Department of Neurology and Neurological Rehabilitation Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)School of MedicineTongji UniversityShanghaiChina Department of Rehabilitation Shanghai Pudong HospitalFudan University Pudong Medical CenterShanghaiChina Key Laboratory of Cellular Physiology(Shanxi Medical University) Ministry of Educationand the Department of PhysiologyShanxi Medical UniversityTaiyuanShanxi ProvinceChina Key Laboratory of Central CNS Regeneration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina

Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been *** studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous ***,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been *** the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different *** pain was reduced only in mice that engaged in high-intensity *** resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor ***,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal *** findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.

关键词： central sensitization chemerin receptor 23 chronic post-ischemia pain complex regional pain syndrome exercise-induced analgesia microglia neuroinflammation resolvin E1 spinal cord swimming

Evolution of the ErbB gene family and analysis of regulators of Egfr expression during development of the rat spinal cord

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Neural Regeneration Research 2022年第11期17卷 2484-2490页

作者： Yu Zhang Tao Zhang Lian Xu Ye Zhu Li-Li Zhao Xiao-Di Li Wei-Wei Yang Jing Chen Miao Gu Xiao-Song Gu Jian Yang School of Medicine&Holistic Integrative Medicine Nanjing University of Chinese MedicineNanjingJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education Co-innovation Center of NeuroregenerationNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsNantong UniversityNantongJiangsu ProvinceChina

Egfr,a member of the ErbB gene family,plays a critical role in tissue development and homeostasis,wound healing,and ***,expression and regulators of Egfr during spinal cord development remain poorly *** this study,we investigated ErbB evolution and analyzed co-expression modules,miRNAs,and transcription factors that may regulate Egfr expression in *** found that ErbB family members formed via Egfr duplication in the ancient ve rtebrates but dive rged after speciation of *** identified a module that was co-expressed with Egfr,which involved cell proliferation and blood vessel *** predicted 25 miRNAs and nine transcription factors that may regulate Egfr ***-luciferase reporter assays showed six out of nine transcription factors significantly affected Egfr promoter reporter *** of these transcription factors(KLF1 and STAT3)inhibited the Egfr promoter repo rter,whereas four transcription factors(including FOXA2)activated the Egfr promoter ***-time PCR and immunofluorescence expe riments showed high expression of FOXA2 during the embryonic period and FOXA2 was expressed in the floor plate of the spinal cord,suggesting the importance of FOXA2 during embryonic spinal cord *** the importance of Egfr in embryonic spinal cord development,wound healing,and disease(specifically in cancer),regulatory elements identified in this study may provide candidate targets for nerve regeneration and disease treatment in the future.

关键词： co-expression Egfr evolution FOXA2 gene expression miRNA spinal cord transcription factor

Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos

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Neural Regeneration Research 2023年第9期18卷 2011-2018页

作者： Bing-Qiang He Ai-Cheng Li Yu-Xuan Hou Hui Li Xing-Yuan Zhang Hui-Fei Hao Hong-Hua Song Ri-Xin Cai Ying-Jie Wang Yue Zhou Yong-Jun Wang Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co-innovation Center of NeuroregenerationMedical School of Nantong UniversityNantongJiangsu ProvinceChina Department of Rehabilitation Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

The low intrinsic growth capacity of neurons and an injury-induced inhibitory milieu are major contributo rs to the failure of sensory and motor functional recovery following spinal cord *** shock transcription factor 1(HSF1),a master regulator of the heat shock response,plays neurogenetic and neuroprotective roles in the damaged or diseased central nervous ***,the underlying mechanism has not been fully *** the present study,we used a gecko model of spontaneous nerve regeneration to investigate the potential roles of gecko HSF1(gHSF1) in the regulation of neurite outgrowth and inflammatory inhibition of macrophages following spinal cord ***1 expression in neurons and microglia at the lesion site increased dramatically immediately after tail ***1 ove rexpression in gecko primary neuro ns significantly promoted axonal growth by suppressing the expression of suppressor of cytokine signaling-3,and fa cilitated neuro nal survival via activation of the mitogen-activated extracellular signal-regulated kinase/extracellular regulated protein kinases and phosphatidylinositol 3-kinase/protein kinase B ***,gHSF1 efficiently inhibited the macrophagemediated inflammatory response by inactivating 1kappa B-alpha/NF-kappaB *** findings show that HSF1 plays dual roles in promoting axonal regrowth and inhibiting leukocyte inflammation,and provide new avenues of investigation for promoting spinal co rd injury repair in mammals.

关键词： apoptosis gecko heat shock factor 1 inflammation neuron regeneration spinal cord suppressor of cytokine signaling-3

Effects of targeted muscle reinnervation on spinal cord motor neurons in rats following tibial nerve transection

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Neural Regeneration Research 2022年第8期17卷 1827-1832页

作者： Wei Lu Jian-Ping Li Zhen-Dong Jiang Lin Yang Xue-Zheng Liu Department of Human Anatomy School of Basic Medical ScinencesGuangxi Medical UniversityNanningGuangxi Zhuang Autonomous RegionChina Department of Human Anatomy Zhuhai Campus of Zunyi Medical UniversityZhuhaiGuangdong ProvinceChina

Targeted muscle reinnervation(TMR)is a surgical procedure used to transfer residual peripheral nerves from amputated limbs to targeted muscles,which allows the target muscles to become sources of motor control information for function ***,the effect of TMR on injured motor neurons is still *** this study,we aimed to explore the effect of hind limb TMR surgery on injured motor neurons in the spinal cord of rats after tibial nerve *** found that the reduction in hind limb motor function and atrophy in mice caused by tibial nerve transection improved after *** enhanced nerve regeneration by increasing the number of axons and myelin sheath thickness in the tibial nerve,increasing the number of anterior horn motor neurons,and increasing the number of choline acetyltransferase-positive cells and immunofluorescence intensity of synaptophysin in rat spinal *** findings suggest that TMR may enable the reconnection of residual nerve fibers to target muscles,thus restoring hind limb motor function on the injured side.

关键词： function reconstruction motor neuron nerve injury nerve implant Nissl staining spinal cord synaptophysin targeted muscle reinnervation tibial nerve transection

Serum response factor promotes axon regeneration following spinal cord transection injury

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Neural Regeneration Research 2023年第9期18卷 1956-1960页

作者： Guo-Ying Feng Nai-Li Zhang Xiao-Wei Liu Ling-Xi Tong Chun-Lei Zhang Shuai Zhou Lu-Ping Zhang Fei Huang Institute of Neurobiology Binzhou Medical UniversityLaishanShandong ProvinceChina School of Health and Life Sciences University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Studies have snown that serum response factor is beneficaial for axonar regeneration of peripheral ***,Its role after central nervous system injury remains unclear. In this study,we established a rat model of T9-T10 spinal cord transection *** found that the expression of serum response factor in injured spinal cord gray matter neurons gradually increased with time,reached its peak on the 7^(th) day,and then gradually *** investigate the role of serum response factor,we used lentivirus vecto rs to ove rexpress and silence serum response factor in spinal cord *** found that overexpression of serum response factor promoted motor function recovery in rats with spinal cord *** observation of biotinylated dextran amine anterograde tra cing showed that ove rexpression of serum response factor increased nerve fibers in the injured spinal co ***,transmission electron microscopy showed that axon and myelin sheath morphology was *** serum response factor had the opposite effects of ove *** findings suggest that serum response factor plays a role in the recovery of motor function after spinal cord *** underlying mechanism may be related to the regulation of axonal regeneration.

关键词： axon growth associated protein 43 motor function myelin sheath neuron regeneration serum response factor spinal cord spinal cord transection