• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

实验性 SCI 后慢性痛觉过敏和多水平神经炎症反应共存：神经病理性疼痛的系统分析方法。

Coexistence of chronic hyperalgesia and multilevel neuroinflammatory responses after experimental SCI: a systematic approach to profiling neuropathic pain.

机构信息

Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA.

Laboratory of SCI, Stem Cell and Recovery Neurobiology Research, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital Network, Mass General Brigham, and Harvard Medical School, 300 1St Avenue, Charlestown Navy Yard, Boston, MA, 02129, USA.

出版信息

J Neuroinflammation. 2022 Oct 29;19(1):264. doi: 10.1186/s12974-022-02628-2.

DOI:10.1186/s12974-022-02628-2
PMID:36309729
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9617391/
Abstract

BACKGROUND

People with spinal cord injury (SCI) frequently develop neuropathic pain (NP) that worsens disability and diminishes rehabilitation efficacy. Chronic NP is presently incurable due to poor understanding of underlying mechanisms. We hypothesized that multilocus neuroinflammation (NIF) might be a driver of SCI NP, and tested it by investigating whether NP coexisted with central NIF, neurotransmission (NTM), neuromodulation (NML) and neuroplasticity (NPL) changes post-SCI.

METHODS

Female Sprague-Dawley rats (230-250 g) with T10 compression or laminectomy were evaluated for physical conditions, coordinated hindlimb functions, neurological reflexes, and mechanical/thermal sensitivity thresholds at 1 day post-injury (p.i.) and weekly thereafter. Eight weeks p.i., central nervous system tissues were histochemically and immunohistochemically characterized for parameters/markers of histopathology and NIF/NTM/NML/NPL. Also analyzed was the correlative relationship between levels of selected biomarkers and thermosensitivity thresholds via statistical linear regression.

RESULTS

SCI impaired sensorimotor functions, altered reflexes, and produced spontaneous pain signs and hypersensitivity to evoked nociceptive, mechanical, and thermal inputs. Only injured spinal cords exhibited neural lesion, microglia/astrocyte activation, and abnormal expression of proinflammatory cytokines, as well as NIF/NTM/NML/NPL markers. Brains of SCI animals displayed similar pathophysiological signs in the gracile and parabrachial nuclei (GrN and PBN: sensory relay), raphe magnus nucleus and periaqueduct gray (RMN and PAG: pain modulation), basolateral amygdala (BLA: emotional-affective dimension of pain), and hippocampus (HPC: memory/mood/neurogenesis). SCI augmented sensory NTM/NPL (GrN and PBN); increased GAD67 (PAG) level; reduced serotonin (RMN) and fear-off neuronal NTR2 (BLA) expressions; and perturbed neurogenesis (HPC).

CONCLUSION

T10 compression caused chronic hyperalgesia that coexisted with NIF/NTM/NML/NPL responses at multilevel neuroaxis centers. The data have provided multidimensional biomarkers as new mechanistic leads to profile SCI NP for therapeutic/therapy development.

摘要

背景

脊髓损伤（SCI）患者常发生神经病理性疼痛（NP），这会加重残疾并降低康复效果。由于对潜在机制缺乏了解，目前慢性 NP 无法治愈。我们假设多部位神经炎症（NIF）可能是 SCI NP 的驱动因素，并通过研究 SCI 后 NP 是否与中枢 NIF、神经传递（NTM）、神经调节（NML）和神经可塑性（NPL）变化共存来验证这一假设。

方法

230-250 克雌性 Sprague-Dawley 大鼠，T10 受压或椎板切除术，于损伤后 1 天（p.i.）及此后每周评估其身体状况、协调后肢功能、神经反射和机械/热感觉阈值。8 周 p.i.时，对中枢神经系统组织进行组织化学和免疫组织化学分析，以评估组织病理学和 NIF/NTM/NML/NPL 参数/标志物。还通过统计线性回归分析，分析了选定生物标志物水平与热敏阈值之间的相关性。

结果

SCI 损伤了感觉运动功能，改变了反射，并产生了自发性疼痛迹象和对诱发的伤害性、机械性和热输入的超敏反应。只有损伤的脊髓才表现出神经病变、小胶质细胞/星形胶质细胞激活和促炎细胞因子的异常表达，以及 NIF/NTM/NML/NPL 标志物。SCI 动物的大脑在薄束核和臂旁核（GrN 和 PBN：感觉传递）、中缝大核和导水管周围灰质（RMN 和 PAG：疼痛调节）、基底外侧杏仁核（BLA：疼痛的情绪-情感维度）和海马（HPC：记忆/情绪/神经发生）中表现出类似的病理生理学迹象。SCI 增强了感觉 NTM/NPL（GrN 和 PBN）；增加了 GAD67（PAG）水平；降低了血清素（RMN）和恐惧神经元 NTR2（BLA）的表达；并扰乱了神经发生（HPC）。

结论

T10 压迫导致慢性痛觉过敏，同时伴有多水平神经轴中心的 NIF/NTM/NML/NPL 反应。这些数据提供了多维生物标志物，为 SCI NP 的治疗/治疗开发提供了新的机制线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/69ed4af029db/12974_2022_2628_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/eb8424801aed/12974_2022_2628_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/50f19839b19e/12974_2022_2628_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/d588b2a4260e/12974_2022_2628_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/2fc3a82d8bb2/12974_2022_2628_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/80c9efb177a3/12974_2022_2628_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/c357cc6b5e7b/12974_2022_2628_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/531f15ec8970/12974_2022_2628_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/c0d280825d98/12974_2022_2628_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/69ed4af029db/12974_2022_2628_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/eb8424801aed/12974_2022_2628_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/50f19839b19e/12974_2022_2628_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/d588b2a4260e/12974_2022_2628_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/2fc3a82d8bb2/12974_2022_2628_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/80c9efb177a3/12974_2022_2628_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/c357cc6b5e7b/12974_2022_2628_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/531f15ec8970/12974_2022_2628_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/c0d280825d98/12974_2022_2628_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e6/9617391/69ed4af029db/12974_2022_2628_Fig9_HTML.jpg

相似文献

1
Coexistence of chronic hyperalgesia and multilevel neuroinflammatory responses after experimental SCI: a systematic approach to profiling neuropathic pain.实验性 SCI 后慢性痛觉过敏和多水平神经炎症反应共存：神经病理性疼痛的系统分析方法。
J Neuroinflammation. 2022 Oct 29;19(1):264. doi: 10.1186/s12974-022-02628-2.
2
Anti-inflammatory effects of Metformin improve the neuropathic pain and locomotor activity in spinal cord injured rats: introduction of an alternative therapy.二甲双胍的抗炎作用改善脊髓损伤大鼠的神经性疼痛和运动活性：一种替代疗法的引入。
Spinal Cord. 2018 Nov;56(11):1032-1041. doi: 10.1038/s41393-018-0168-x. Epub 2018 Jun 29.
3
Voluntary exercise ameliorates neuropathic pain by suppressing calcitonin gene-related peptide and ionized calcium-binding adapter molecule 1 overexpression in the lumbar dorsal horns in response to injury to the cervical spinal cord.自愿运动通过抑制降钙素基因相关肽和钙结合蛋白配体 1 在腰椎背角的过度表达来改善神经性疼痛，这是对颈脊髓损伤的反应。
Exp Neurol. 2022 Aug;354:114105. doi: 10.1016/j.expneurol.2022.114105. Epub 2022 May 5.
4
Cervical spinal cord injury-induced neuropathic pain in male mice is associated with a persistent pro-inflammatory macrophage/microglial response in the superficial dorsal horn.雄性小鼠脊髓颈段损伤诱导的神经性疼痛与浅背角中持续存在的促炎型巨噬细胞/小胶质细胞反应有关。
Exp Neurol. 2021 Sep;343:113757. doi: 10.1016/j.expneurol.2021.113757. Epub 2021 May 12.
5
Administration of ONO-2506 suppresses neuropathic pain after spinal cord injury by inhibition of astrocytic activation.ONO-2506 的给药通过抑制星形胶质细胞的激活来抑制脊髓损伤后的神经性疼痛。
Spine J. 2019 Aug;19(8):1434-1442. doi: 10.1016/j.spinee.2019.04.006. Epub 2019 Apr 8.
6
Chronic at-level thermal hyperalgesia following rat cervical contusion spinal cord injury is accompanied by neuronal and astrocyte activation and loss of the astrocyte glutamate transporter, GLT1, in superficial dorsal horn.大鼠颈髓挫伤性脊髓损伤后持续存在的节段性热痛觉过敏，伴有浅表背角神经元和星形胶质细胞激活以及星形胶质细胞谷氨酸转运体GLT1缺失。
Brain Res. 2014 Sep 18;1581:64-79. doi: 10.1016/j.brainres.2014.05.003. Epub 2014 May 14.
7
Exploring acute-to-chronic neuropathic pain in rats after contusion spinal cord injury.探索大鼠脊髓挫伤损伤后急性至慢性神经性疼痛
Exp Neurol. 2017 Sep;295:46-54. doi: 10.1016/j.expneurol.2017.05.011. Epub 2017 May 25.
8
Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat.丙烯醛参与大鼠脊髓损伤后的感觉和行为过敏。
J Neurochem. 2014 Mar;128(5):776-786. doi: 10.1111/jnc.12500. Epub 2013 Nov 13.
9
Role of Rho-associated coiled-coil containing protein kinase in the spinal cord injury induced neuropathic pain.Rho 相关卷曲螺旋蛋白激酶在脊髓损伤诱导的神经性疼痛中的作用。
Spine J. 2021 Feb;21(2):343-351. doi: 10.1016/j.spinee.2020.08.011. Epub 2020 Aug 25.
10
Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury.脊髓损伤后，外周和中枢敏化作用导致脊髓损伤后中枢性神经病理性疼痛。
Pain. 2009 Dec 15;147(1-3):265-76. doi: 10.1016/j.pain.2009.09.030. Epub 2009 Oct 22.

引用本文的文献

1
Astrocytic Inducible Nitric Oxide Synthase Upregulation Contributes to Chronic Below-Level Neuropathic Pain Following Spinal Cord Injury in Male Rats.星形胶质细胞诱导型一氧化氮合酶上调促成雄性大鼠脊髓损伤后慢性轻度神经性疼痛
Eur J Pain. 2025 Jul;29(6):e70047. doi: 10.1002/ejp.70047.
2
Repeated Administrations of Polyphenolic Extracts Prevent Chronic Reflexive and Non-Reflexive Neuropathic Pain Responses by Modulating Gliosis and CCL2-CCR2/CX3CL1-CX3CR1 Signaling in Spinal Cord-Injured Female Mice.多次给予多酚提取物可通过调节脊髓损伤雌性小鼠的胶质增生和CCL2-CCR2/CX3CL1-CX3CR1信号通路，预防慢性反射性和非反射性神经性疼痛反应。
Int J Mol Sci. 2025 Apr 2;26(7):3325. doi: 10.3390/ijms26073325.
3

本文引用的文献

1
Analgesic effect of gastrin-releasing peptide in the dorsal horn.胃泌素释放肽在背角中的镇痛作用。
Mol Pain. 2022 Apr;18:17448069221108965. doi: 10.1177/17448069221108965.
2
Spinal ascending pathways for somatosensory information processing.躯体感觉信息处理的脊髓上行通路。
Trends Neurosci. 2022 Aug;45(8):594-607. doi: 10.1016/j.tins.2022.05.005. Epub 2022 Jun 12.
3
A spinal microglia population involved in remitting and relapsing neuropathic pain.参与缓解和复发性神经病理性疼痛的脊髓小胶质细胞群体。
SGK1 upregulation in GFAP neurons in the frontal association cortex protects against neuronal apoptosis after spinal cord injury.
额叶联合皮质中胶质纤维酸性蛋白（GFAP）神经元中血清和糖皮质激素诱导激酶1（SGK1）的上调可保护脊髓损伤后神经元免于凋亡。
Cell Death Dis. 2025 Apr 2;16(1):237. doi: 10.1038/s41419-025-07542-y.
4
An engineering-reinforced extracellular vesicle-integrated hydrogel with an ROS-responsive release pattern mitigates spinal cord injury.一种具有活性氧响应释放模式的工程强化细胞外囊泡整合水凝胶可减轻脊髓损伤。
Sci Adv. 2025 Apr 4;11(14):eads3398. doi: 10.1126/sciadv.ads3398. Epub 2025 Apr 2.
5
Neuropathic Pain Induced by Spinal Cord Injury from the Glia Perspective and Its Treatment.脊髓损伤引起的神经病理性疼痛的神经胶质细胞相关机制及其治疗。
Cell Mol Neurobiol. 2024 Nov 28;44(1):81. doi: 10.1007/s10571-024-01517-x.
6
Concurrent Oncolysis and Neurolesion Repair by Dual Gene-Engineered hNSCs in an Experimental Model of Intraspinal Cord Glioblastoma.双重基因工程 hNSC 治疗脊髓胶质母细胞瘤的协同溶瘤与神经保护作用的实验研究。
Cells. 2024 Sep 11;13(18):1522. doi: 10.3390/cells13181522.
7
Combined transplantation of hiPSC-NSC and hMSC ameliorated neuroinflammation and promoted neuroregeneration in acute spinal cord injury.人诱导多能干细胞-神经干细胞与骨髓间充质干细胞联合移植改善急性脊髓损伤的神经炎症反应和促进神经再生。
Stem Cell Res Ther. 2024 Mar 5;15(1):67. doi: 10.1186/s13287-024-03655-x.
8
T12-L3 Nerve Transfer-Induced Locomotor Recovery in Rats with Thoracolumbar Contusion: Essential Roles of Sensory Input Rerouting and Central Neuroplasticity.T12-L3 神经转移诱导大鼠胸腰段挫伤后运动功能恢复：感觉输入改道和中枢神经可塑性的重要作用。
Cells. 2023 Dec 8;12(24):2804. doi: 10.3390/cells12242804.
9
Impact of vitamin D on the prognosis after spinal cord injury: A systematic review.维生素D对脊髓损伤后预后的影响：一项系统评价。
Front Nutr. 2023 Feb 14;10:920998. doi: 10.3389/fnut.2023.920998. eCollection 2023.
10
Direct Cell Reprogramming and Phenotypic Conversion: An Analysis of Experimental Attempts to Transform Astrocytes into Neurons in Adult Animals.直接细胞重编程和表型转化：成年动物中星形胶质细胞向神经元转化的实验尝试分析。
Cells. 2023 Feb 14;12(4):618. doi: 10.3390/cells12040618.
Science. 2022 Apr;376(6588):86-90. doi: 10.1126/science.abf6805. Epub 2022 Mar 31.
4
Current Understanding of the Neural Circuitry in the Comorbidity of Chronic Pain and Anxiety.慢性疼痛与焦虑共病的神经回路的当前认识。
Neural Plast. 2022 Feb 15;2022:4217593. doi: 10.1155/2022/4217593. eCollection 2022.
5
Ventrolateral periaqueductal gray matter integrative system of defense and antinociception.腹外侧水管周围灰质防御和镇痛整合系统。
Pflugers Arch. 2022 Apr;474(4):469-480. doi: 10.1007/s00424-022-02672-0. Epub 2022 Feb 24.
6
A New Potential Antidepressant: Dexmedetomidine Alleviates Neuropathic Pain-Induced Depression by Increasing Neurogenesis in the Hippocampus.一种新型潜在抗抑郁药：右美托咪定通过增加海马体神经发生来减轻神经性疼痛诱导的抑郁。
Pharmacology. 2022;107(5-6):317-329. doi: 10.1159/000521737. Epub 2022 Feb 23.
7
Long term effects of 24-h-restraint stress on the connectivity and structure of interneurons in the basolateral amygdala.24 小时束缚应激对基底外侧杏仁核中间神经元连接和结构的长期影响。
Prog Neuropsychopharmacol Biol Psychiatry. 2022 Apr 20;115:110512. doi: 10.1016/j.pnpbp.2022.110512. Epub 2022 Jan 20.
8
Inflammation after spinal cord injury: a review of the critical timeline of signaling cues and cellular infiltration.脊髓损伤后的炎症反应：信号通路和细胞浸润的关键时间进程综述。
J Neuroinflammation. 2021 Dec 7;18(1):284. doi: 10.1186/s12974-021-02337-2.
9
High-resolution mapping and digital atlas of subcortical regions in the macaque monkey based on matched MAP-MRI and histology.基于匹配的 MAP-MRI 和组织学的猕猴皮质下区域的高分辨率图谱绘制和数字图谱。
Neuroimage. 2021 Dec 15;245:118759. doi: 10.1016/j.neuroimage.2021.118759. Epub 2021 Nov 25.
10
Supraspinal Sensorimotor and Pain-Related Reorganization after a Hemicontusion Rat Cervical Spinal Cord Injury.半脱位型颈脊髓损伤后脊髓以上感觉运动和痛觉相关重组。
J Neurotrauma. 2021 Dec;38(24):3393-3405. doi: 10.1089/neu.2021.0190.