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

Millecamps, Magalia,b; Stone, Laura S.a,b,c,d,*

doi: 10.1097/j.pain.0000000000001284
Research Paper

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.

Axial and radiating low back pain take months to fully develop after L4/5 intervertebral disc injury and are associated with increased innervation and disc narrowing.

aFaculty of Dentistry, McGill University, Montreal, QC, Canada

bAlan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada

Departments of cAnesthesiology and

dPharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, QC, Canada

Corresponding author. Address: Alan Edwards Centre for Research on Pain, Faculty of Dentistry, McGill University, 740 Dr Penfield Ave, Suite 3200, Montreal, QC H3G 0G1, Canada. Tel.: 514-398-7203 x00039; fax: 514-398-8121. E-mail address: (L.S. Stone).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

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Received January 23, 2018

Received in revised form April 27, 2018

Accepted May 11, 2018

© 2018 International Association for the Study of Pain
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