Delayed onset of persistent discogenic axial and radiating pain after a single-level lumbar intervertebral disc injury in mice

Magali Millecamps, Laura S. Stone

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Low back pain (LBP) is associated with both axial discomfort and radiating leg pain. Although intervertebral discs are suspected as the source of pain in some individuals, the relationship between disc degeneration and back pain remains controversial. The goals of this study were to investigate the long-Term impact of L4/L5 disc puncture on disc degeneration and the subsequent emergence, persistence, and underlying mechanisms of axial and radiating LBP in mice. L4 to L5 discs were punctured on the ventral aspect with a 30 gauge needle in 3-month old female CD1 mice, and the development of behavioral signs of axial discomfort (tail suspension and grip force), radiating hypersensitivity (von Frey and acetone), and motor impairment (rotarod) were monitored. Disc degeneration was assessed using X-ray, T2 magnetic resonance imaging, and histology, and persisted for up to 1 year. Innervation was quantified by immunohistochemistry using the pan-neuronal marker PGP9.5. Behavioural signs of axial discomfort peaked 3 to 9 months after injury. During the peak, local nerve density was increased. A transient increase in hypersensitivity to cold, suggestive of radiating pain, was observed 2 weeks after injury. Radiating pain then reemerged 9 to 12 months after injury in half the animals and correlated with increased dorsal innervation and reduced disc height at these late time points. In summary, a single-level disc injury is sufficient to induce prolonged disc degeneration and delayed axial and radiating pain. This model will be useful to investigate underlying mechanisms and potential therapeutic strategies for discogenic LBP.

Original languageEnglish (US)
Pages (from-to)1843-1855
Number of pages13
Issue number9
StatePublished - Sep 1 2018
Externally publishedYes

Bibliographical note

Funding Information:
Supported by a CIHR/CPS/AstraZeneca Biology of Pain Young Investigator Grant XCP-83755 to L.S. Stone, CIHR operating Grants MOP–102586 and MOP-126046 to L.S. Stone and M. Millecamps, and a pain research grant from The Louise and Alan Edwards Foundation to L.S. Stone and M. Millecamps. L.S. Stone reports grants from Canadian Institutes of Health Research, grants from Louise and Alan Edwards Foundation, and nonfinancial support from Pfizer, during the conduct of the study.

Publisher Copyright:
© 2018 Lippincott Williams and Wilkins. All rights reserved.


  • Animal model
  • Discogenic low back pain
  • Intervertebral disc degeneration
  • MRI
  • Pain behaviour


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