Behavioral signs of axial low back pain and motor impairment correlate with the severity of intervertebral disc degeneration in a mouse model.
BACKGROUND
Chronic low back pain is debilitating and difficult to treat. Depending on the etiology, responses to treatments vary widely. Although chronic low back pain is frequently related to intervertebral disc degeneration, the relationship between disc degeneration severity and clinical symptoms are still poorly understood. In humans, studies investigating the relationship between disc degeneration severity and low back pain are limited by the difficulty of obtaining disc samples from well-characterized patients and pain-free controls. We have previously described the secreted protein, acidic, rich in cysteine (SPARC)-null mouse model of chronic low back pain. SPARC is a matricellular protein involved in regulating the assembly and composition of extracellular matrix. The SPARC-null mice develop age-dependent disc degeneration of increasing severity accompanied by behavioral signs suggestive of axial low back pain, radiating leg pain, and motor impairment. The existence of this model allows for examination of the relationships between clinical symptoms in vivo and pathological signs of disc degeneration ex vivo.


OBJECTIVE
The goal of this study was to explore the relationship between behavioral signs of pain and the severity of lumbar disc degeneration using the SPARC-null mouse model of disc degeneration-related low back pain.


METHODS
This study used a cross-sectional, multiple-cohort behavioral and histological study of disc degeneration and behavioral symptoms in a mouse model of low back pain associated with disc degeneration.


METHODS
SPARC-null and wild-type control mice ranging from 6 to 78 weeks of age were used in this study. The severity of disc degeneration was determined by ex vivo analysis of the lumbar spine using colorimetric histological staining and a scoring system adapted from the Pfirrmann scale. Behavioral signs of axial low back pain, radiating leg pain, and motor impairment were quantified as tolerance to axial stretching in the grip force assay, hypersensitivity to cold or mechanical stimuli on the hindpaw (acetone and von Frey tests), and latency to fall in the rotarod assay, respectively.


RESULTS
The SPARC-null mice exhibited decreased tolerance to axial stretching, hindpaw cold hypersensitivity, and motor impairment compared with age-matched control mice. The severity of disc degeneration increased with age in both SPARC-null and control mice and by 78 weeks of age, the same proportion of lumbar discs were abnormal in SPARC-null and control mice. However, the degree of degeneration was more severe in the SPARC-null mice. In both SPARC-null and control mice, tolerance to axial stretching but not hindpaw cold sensitivity correlated with disc degeneration severity. Motor impairment correlated with degeneration severity in the SPARC-null mice only.


CONCLUSIONS
These data suggest that internal disc disruption contributes to axial low back pain and motor impairment but not to radiating leg pain. These results have implications for the optimization of mechanism-based treatments strategies.
Faculty of Dentistry, McGill University, 2001 McGill College Avenue, Suite 500, Montreal, Quebec, Canada H3A 1G1; Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Ave, Suite 3200, Montreal, Quebec, Canada H3G 0G1.
Magali
M
Millecamps
Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Ave, Suite 3200, Montreal, Quebec, Canada H3G 0G1.
Jan T
JT
Czerminski
Brain Imaging Centre, Douglas Mental Health University Institute, 6875 Blvd Lasalle, Montreal, Quebec, Canada H4H 1R3.
Axel P
AP
Mathieu
Faculty of Dentistry, McGill University, 2001 McGill College Avenue, Suite 500, Montreal, Quebec, Canada H3A 1G1; Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Ave, Suite 3200, Montreal, Quebec, Canada H3G 0G1; McGill Scoliosis & Spine Research Group, McGill University, 1650 Cedar Ave, Office B5-158.4, Montreal, Quebec, Canada H3G1A4; Integrated Program in Neuroscience, McGill University, 3801University Street, Room 141, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4; Department of Anesthesiology, Faculty of Medicine, McGill University, 3655 Promenade Sir William Osler, 12th Floor, Montreal, Quebec, Canada H3G 1Y6; Department of Pharmacology & Therapeutics, Faculty of Medicine, McGill University, 3655 Promenade Sir-William-Osler, Room 1325, Montreal, Quebec, Canada H3G 1Y6. Electronic address: laura.s.stone@mcgill.ca.
Laura S
LS
Stone
D000368:Aged; D000818:Animals; D005260:Female; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000473:pathology / Q000503:physiopathology*; D008124:Locomotion; D017116:Low Back Pain / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL
Animal model; Correlation; Degenerative disc disease; Histology; Intervertebral disc; Low back pain; SPARC