SDF-1/CXCR4 Activates ERK and PI3K/AKT Signaling Contributing to the Pathogenesis of Radicular Pain Induced by Autograft of Nucleus Pulposus

WEI Ming; GAO Feng-jiao; YANG Lin; SUN Lai-bao; ZOU Xue-nong; HUANG Wen-qi

doi:10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0107

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SDF-1/CXCR4 Activates ERK and PI3K/AKT Signaling Contributing to the Pathogenesis of Radicular Pain Induced by Autograft of Nucleus Pulposus

Basic Research | 更新时间：2024-02-19

- SDF-1/CXCR4 Activates ERK and PI3K/AKT Signaling Contributing to the Pathogenesis of Radicular Pain Induced by Autograft of Nucleus Pulposus
- Journal of Sun Yat-sen University(Medical Sciences) Vol. 42, Issue 3, Pages: 373-380(2021)
- 作者机构：
  
  1.中山大学附属第一医院麻醉科，广东广州 510080
  2.番禺区中心医院麻醉科，广东广州 511400
  3.广东省骨科学重点实验室，广东广州 510700
- 作者简介：
  
  HUANG Wen-qi； E-mail： huangwq@mail.sysu.edu.cn
- 基金信息：
- DOI：10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0107
  CLC： R364.5
- Received：18 March 2021，
  
  Published：20 May 2021
- 稿件说明：
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魏明,高凤娇,杨琳等.SDF-1/CXCR4激活ERK和PI3K/AKT通路介导髓核致炎根性疼痛[J].中山大学学报（医学科学版）,2021,42(03):373-380.

WEI Ming,GAO Feng-jiao,YANG Lin,et al.SDF-1/CXCR4 Activates ERK and PI3K/AKT Signaling Contributing to the Pathogenesis of Radicular Pain Induced by Autograft of Nucleus Pulposus[J].Journal of Sun Yat-sen University(Medical Sciences),2021,42(03):373-380.
魏明,高凤娇,杨琳等.SDF-1/CXCR4激活ERK和PI3K/AKT通路介导髓核致炎根性疼痛[J].中山大学学报（医学科学版）,2021,42(03):373-380. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0107.

WEI Ming,GAO Feng-jiao,YANG Lin,et al.SDF-1/CXCR4 Activates ERK and PI3K/AKT Signaling Contributing to the Pathogenesis of Radicular Pain Induced by Autograft of Nucleus Pulposus[J].Journal of Sun Yat-sen University(Medical Sciences),2021,42(03):373-380. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0107.

摘要

目的

探讨基质细胞衍生因子1/趋化因子CXC受体4（SDF-1/CXCR4）通路在髓核致炎根性疼痛中的作用及机制。

方法

分为三部分：① 26只大鼠随机分为假手术组和模型组，分别行假手术或髓核自体移植。Von Frey 纤维丝测量大鼠机械撤足阈值（PWT）的变化； Western blot法检测大鼠脊髓中SDF-1、CXCR4，磷酸化细胞外信号调节激酶（pERK）和磷酸化蛋白激酶B（pAKT）表达水平；免疫荧光染色定位SDF-1、CXCR4的表达细胞。② 54只大鼠随机分为假手术组、模型组、溶剂组、AMD3100组、SDF-1中和抗体组、对照Ig G组。鞘内注射相应药物，测量大鼠PWT的变化和大鼠脊髓中pERK和pAKT的表达变化。③ 18只大鼠随机分为溶剂组、U0126组、LY294002组，鞘内注射相应药物，测量大鼠PWT的变化。

结果

① 髓核自体移植使大鼠PWT下降（

＜0.001），脊髓中SDF-1、CXCR4、pERK，pAKT表达上调（

＜0.05），SDF-1主要与脊髓中神经元共表达，CXCR4 与神经元和星形胶质细胞共表达。② 鞘内注射SDF-1中和抗体或CXCR4抑制剂AMD3100升高髓核自体移植大鼠的PWT（

＜0.05），并使髓核自体移植大鼠脊髓中pERK和pAKT表达下调（

＜0.05）。③ 鞘内给予MEK抑制剂U0126或PI3K抑制剂LY294002可升高髓核自体移植大鼠PWT（

＜0.05）。

结论

SDF-1/CXCR4通过激活ERK和PI3K/AKT通路介导髓核致炎根性疼痛。

Abstract

Objective

To investigate the effect and mechanism of SDF-1/CXCR4 in radicular pain induced by autograft of nucleus pulposus.

Methods

Three parts were included. ① 26 rats were randomly divided into sham group and model group. Autograft of nucleus pulposus was done in model group. Paw withdrawal threshold （PWT） was tested by von Fray filaments. The expression of SDF-1， CXCR4， pERK and pAKT of spinal cord was tested by western blot. Immunofluorescence staining was used to locate the expression of SDF-1 and CXCR4. ② 54 rats were randomly and equally divided into sham group， model group， vehicle group， SDF-1 neutralizing antibody group， AMD3100 group， and isotype IgG group. Drug was administered intrathecally. PWT and the expression of pERK and pAKT of spinal cord were tested. ③ 18 rats were randomly and equally divided into model group， U0126 group and LY294002 group. Drug was administered intrathecally. PWT was tested.

Results

① Autologous nucleus pulposus transplantation in rats reduced PWT （

＜0.001） and increased the expressions of SDF-1， CXCR4， pERK and pAKT in spinal cord of rats （

＜0.05）. SDF-1 was mainly co-expressed with neuron， while CXCR4 was co-expressed with neuron and astrocyte. ② SDF-1 neutralizing antibody and CXCR4 inhibitor AMD3100 reduced PWT （

＜0.05）. The expression of pERK and pAKT in spinal cord of SDF-1 neutralizing antibody group and AMD3100 group was reduced （

＜0.05）. ③ Intrathecally administration of MEK inhibitor U0126 or PI3K inhibitor LY294002 reduced PWT （

＜0.05）.

Conclusion

SDF-1/CXCR4 activates ERK and PI3K/AKT signaling， which contributes to the pathogenesis of radicular pain induced by autograft of nucleus pulposus.

关键词

Keywords

references

Deyo RA ， Mirza SK . CLINICAL PRACTICE. Herniated Lumbar Intervertebral Disk ［J］. N Engl J Med ， 2016 ， 374 （ 18 ）： 1763 - 1772 .

Altun I . Cytokine profile in degenerated painful intervertebral disc： variability with respect to duration of symptoms and type of disease ［J］. Spine J ， 2016 ， 16 （ 7 ）： 857 - 861 .

Reaux-Le Goazigo A ， Rivat C ， Kitabgi P ， et al . Cellular and subcellular localization of CXCL12 and CXCR4 in rat nociceptive structures： physiological relevance ［J］. Eur J Neurosci ， 2012 ， 36 （ 5 ）： 2619 - 2631 .

Li F ， Xue ZY ， Yuan Y ， et al . Upregulation of CXCR4 through promoter demethylation contributes to inflammatory hyperalgesia in rats ［J］. CNS Neurosci Ther ， 2018 ， 24 （ 10 ）： 947 - 956 .

Shen W ， Hu XM ， Liu YN ， et al . CXCL12 in astrocytes contributes to bone cancer pain through CXCR4-mediated neuronal sensitization and glial activation in rat spinal cord ［J］. J Neuroinflammation ， 2014 ， 11 ： 75 .

Hang LH ， Li SN ， Luo H ， et al . Connexin 43 Mediates CXCL12 production from spinal dorsal horn to maintain bone cancer pain in rats ［J］. Neurochem Res ， 2016 ， 41 （ 5 ）： 1200 - 1208 .

Xing F ， Kong C ， Bai L ， et al . CXCL12/CXCR4 signaling mediated ERK1/2 activation in spinal cord contributes to the pathogenesis of postsurgical pain in rats ［J］. Mol Pain ， 2017 ， 13 ： 1 - 12 .

Yang F ， Sun W ， Luo WJ ， et al . SDF1-CXCR4 signaling contributes to the transition from acute to chronic pain state ［J］. Mol Neurobiol ， 2017 ， 54 （ 4 ）： 2763 - 2775 .

Zhu HY ， Liu X ， Miao X ， et al . Up-regulation of CXCR4 expression contributes to persistent abdominal pain in rats with chronic pancreatitis ［J］. Mol Pain ， 2017 ， 13 ： 1 - 11 .

Xu T ， Zhang XL ， Ou-Yang HD ， et al . Epigenetic upregulation of CXCL12 expression mediates antitubulin chemotherapeutics-induced neuropathic pain ［J］. Pain ， 2017 ， 158 （ 4 ）： 637 - 648 .

Bareiss SK ， Dugan E ， Brewer KL . PI3K mediated activation of GSK-3β reduces at-level primary afferent growth responses associated with excitotoxic spinal cord injury dysesthesias ［J］. Mol Pain ， 2015 ， 11 ： 35 .

Liu C ， Luan S ， OuYang H ， et al . Upregulation of CCL2 via ATF3/c-Jun interaction mediated the Bortezomib-induced peripheral neuropathy ［J］. Brain Behav Immun ， 2016 ， 53 ： 96 - 104 .

Wei M ， Mo SL ， Nabar NR ， et al . Modification of rat model of sciatica induced by lumber disc herniation and the anti-inflammatory effect of osthole given by epidural catheterization ［J］. Pharmacology ， 2012 ， 90 （ 5-6 ）： 251 - 263 .

Chaplan SR ， Bach FW ， Pogrel JW ， et al . Quantitative assessment of tactile allodynia in the rat paw ［J］. J Neurosci Methods ， 1994 ， 53 （ 1 ）： 55 - 63 .

Liu ZY ， Song ZW ， Guo SW ， et al . CXCL12/CXCR4 signaling contributes to neuropathic pain via central sensitization mechanisms in a rat spinal nerve ligation model ［J］. CNS Neurosci Ther ， 2019 ， 25 （ 9 ）： 922 - 936 .

Bai L ， Wang X ， Li Z ， et al . Upregulation of chemokine CXCL12 in the dorsal root ganglia and spinal cord contributes to the development and maintenance of neuropathic pain following spared nerve injury in rats ［J］. Neurosci Bull ， 2016 ， 32 （ 1 ）： 27 - 40 .

Yu Y ， Huang X ， Di Y ， et al . Effect of CXCL12/CXCR4 signaling on neuropathic pain after chronic compression of dorsal root ganglion ［J］. Sci Rep ， 2017 ， 7 （ 1 ）： 5707 .

Li XQ ， Zhang ZL ， Tan WF ， et al . Down-Regulation of CXCL12/CXCR4 expression alleviates ischemia-reperfusion-induced inflammatory pain via inhibiting glial TLR4 activation in the spinal cord ［J］. PloS One ， 2016 ， 11 （ 10 ）： e0163807 .

Li YY ， Li H ， Liu ZL ， et al . Activation of STAT3-mediated CXCL12 up-regulation in the dorsal root ganglion contributes to oxaliplatin-induced chronic pain ［J］. Mol Pain ， 2017 ， 13 ： 1 - 11 .

Hossain MZ ， Unno S ， Ando H ， et al . Neuron-glia crosstalk and neuropathic pain： involvement in the modulation of motor activity in the orofacial region ［J］. Int J Mol Sci ， 2017 ， 18 （ 10 ）： 2051 .

魏绪红，杨涛，宫庆娟，等 . 大鼠脊髓小胶质细胞p38 MAPK介导rrIL-1β诱导的机械痛敏［J］. 中山大学学报（医学科学版）， 2010 ， 31 （ 3 ）： 327 - 331 .

Wei XH ， Yang T ， Gong QJ ， et al . p38 MAPK in spinal microglia mediates mechanical allodynia induced by rrIL-1β ［J］. J Sun Yat-sen Univ （Med Sci）， 2010 ， 31 （ 3 ）： 327 - 331 .

Huang W ， Zhao Y ， Zhu X ， et al . Fluoxetine upregulates phosphorylated-AKT and phosphorylated-ERK1/2 proteins in neural stem cells： evidence for a crosstalk between AKT and ERK1/2 pathways ［J］. J Mol Neurosci ， 2013 ， 49 （ 2 ）： 244 - 249 .

Ebi H ， Costa C ， Faber AC ， et al . PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF， P-Rex1 ［J］. Proc Natl Acad Sci USA ， 2013 ， 110 （ 52 ）： 21124 - 21129 .

Hong SK ， Jeong JH ， Chan AM ， et al . AKT upregulates B-Raf Ser445 phosphorylation and ERK1/2 activation in prostate cancer cells in response to androgen depletion ［J］. Exp Cell Res ， 2013 ， 319 （ 12 ）： 1732 - 1743 .

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