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Mol Pain. 2017 Jan-Dec;13:1744806917733637. doi: 10.1177/1744806917733637.

Src-family kinases activation in spinal microglia contributes to central sensitization and chronic pain after lumbar disc herniation.

Huang Y1, Li Y2, Zhong X2, Hu Y3,4, Liu P3,4, Zhao Y3,4, Deng Z3,4, Liu X2, Liu S1, Zhong Y3,4.

Author information

1
1 Department of Spine Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
2
2 Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
3
3 Department of Physiology, School of Basic Medical Science, 26468 Guangzhou Medical University , Guangzhou, China.
4
4 Department of Neurology, Institute of Neuroscience, Second Affiliated Hospital of 26468 Guangzhou Medical University , Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China.

Abstract

Background Lumbar disc herniation is a major cause of radicular pain, but the underlying mechanisms remain largely unknown. Spinal activation of src-family kinases are involved in the development of chronic pain from nerve injury, inflammation, and cancer. In the present study, the role of src-family kinases activation in lumbar disc herniation-induced radicular pain was investigated. Results Lumbar disc herniation was induced by implantation of autologous nucleus pulposus, harvest from tail, in lumbar 4/5 spinal nerve roots of rat. Behavior test and electrophysiologic data showed that nucleus pulposus implantation induced persistent mechanical allodynia and thermal hyperalgesia and increased efficiency of synaptic transmission in spinal dorsal horn which underlies central sensitization of pain sensation. Western blotting and immunohistochemistry staining revealed that the expression of phosphorylated src-family kinases was upregulated mainly in spinal microglia of rats with nucleus pulposus. Intrathecal delivery of src-family kinases inhibitor PP2 alleviated pain behaviors, decreased efficiency of spinal synaptic transmission, and reduced phosphorylated src-family kinases expression. Furthermore, we found that the expression of ionized calcium-binding adapter molecule 1 (marker of microglia), tumor necrosis factor-α, interleukin 1 -β in spinal dorsal horn was increased in rats with nucleus pulposus. Therapeutic effect of PP2 may be related to its capacity in reducing the expression of these factors. Conclusions These findings suggested that central sensitization was involved in radicular pain from lumbar disc herniation; src-family kinases-mediated inflammatory response may be responsible for central sensitization and chronic pain after lumbar disc herniation.

KEYWORDS:

Src-family kinases; central sensitization; long-term potentiation; lumbar disc herniation; microglia; pro-inflammatory cytokines; radicular pain

PMID:
28952414
PMCID:
PMC5624351
DOI:
10.1177/1744806917733637
[Indexed for MEDLINE]
Free PMC Article

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