Development of an in vivo mouse model of discogenic low back pain

Changgui Shi, Vaskar Das, Xin Li, Ranjan Kc, Sujun Qiu, In Sug O-Sullivan, Richard L. Ripper, Jeffrey S. Kroin, Fackson Mwale, Atiyayein A. Wallace, Bingqian Zhu, Lan Zhao, Andre J. van Wijnen, Mingliang Ji, Jun Lu, Gina Votta-Velis, Wen Yuan, Hee Jeong Im

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Discogenic low back pain (DLBP) is extremely common and costly. Effective treatments are lacking due to DLBP's unknown pathogenesis. Currently, there are no in vivo mouse models of DLBP, which restricts research in this field. The aim of this study was to establish a reliable DLBP model in mouse that captures the pathological changes in the disc and allows longitudinal pain testing. The model was generated by puncturing the mouse lumbar discs (L4/5, L5/6, and L6/S1) and removing the nucleus pulposus using a microscalpel under the microscope. Histology, molecular pathways, and pain-related behaviors were examined. Over 12 weeks post-surgery, animals displayed the mechanical, heat, and cold hyperalgesia along with decreased burrowing and rearing. Histology showed progressive disc degeneration with loss of disc height, nucleus pulposus reduction, proteoglycan depletion, and annular fibrotic disorganization. Immunohistochemistry revealed a substantial increase in inflammatory mediators at 2 and 4 weeks. Nerve growth factor was upregulated from 2 weeks to the end of the experiment. Nerve fiber ingrowth was induced in the injured discs after 4 weeks. Disc-puncture also produced an upregulation of neuropeptides in dorsal root ganglia neurons and an activation of glial cells in the spinal cord dorsal horn. These findings indicate that the cellular and structural changes in discs, as well as peripheral and central nervous system plasticity, paralleled persistent, and robust behavioral pain responses. Therefore, this mouse DLBP model could be used to investigate mechanisms underlying discogenic pain, thereby facilitating effective drug screening and development of treatments for DLBP.

Original languageEnglish (US)
Pages (from-to)6589-6602
Number of pages14
JournalJournal of Cellular Physiology
Volume233
Issue number10
DOIs
StatePublished - Oct 2018

Keywords

  • animal model
  • disc degeneration
  • discogenic pain
  • mouse
  • pain measurement

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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  • Cite this

    Shi, C., Das, V., Li, X., Kc, R., Qiu, S., O-Sullivan, I. S., Ripper, R. L., Kroin, J. S., Mwale, F., Wallace, A. A., Zhu, B., Zhao, L., van Wijnen, A. J., Ji, M., Lu, J., Votta-Velis, G., Yuan, W., & Im, H. J. (2018). Development of an in vivo mouse model of discogenic low back pain. Journal of Cellular Physiology, 233(10), 6589-6602. https://doi.org/10.1002/jcp.26280