Behavioral signs of chronic back pain in the SPARC-null mouse.
METHODS
Secreted Protein, Acidic, and Rich in Cysteine (SPARC)-null mice were examined for behavioral signs of chronic low back and/or radicular pain.


OBJECTIVE
to assess SPARC-null mice as an animal model of chronic low back and/or radicular pain caused by degenerative disc disease.


BACKGROUND
degeneration of intervertebral discs is a major cause of chronic low back and adicular pain in humans. Inactivation of the SPARC gene in mice results in premature intervertebral disc degeneration. The effect of disc degeneration on behavioral measures of chronic pain has not been evaluated in this model.


METHODS
cohorts of young and old (3 and 6-12 months, respectively) SPARC-null and wild-type control mice were screened for behavioral indices of low back and/or radiating pain. Sensitivity to mechanical, cold and heat stimuli, locomotor impairment, and movement-evoked hypersensitivity were determined. Animals were challenged with 3 analgesic agents with different mechanisms: morphine, dexamethasone, and gabapentin.


RESULTS
SPARC-null mice showed signs of movement-evoked discomfort as early as 3 months of age. Hypersensitivity to cold stimuli on both the lower back and hindpaws developed with increasing age. SPARC-null mice had normal sensitivity to tactile and heat stimuli, and locomotor skills were not impaired. The hypersensitivity to cold was reversed by morphine, but not by dexamethasone or gabapentin.


CONCLUSIONS
SPARC-null mice display behavioral signs consistent with chronic low back and radicular pain that we attribute to intervertebral disc degeneration. We hypothesize that the SPARC-null mouse is useful as a model of chronic back pain due to degenerative disc disease.
Millecamps
Magali
M
Alan Edwards Centre for Research on Pain, McGill University,Montreal, Quebec, Canada.
Tajerian
Maral
M
Sage
E Helene
EH
Stone
Laura S
LS
D000367:Age Factors; D000588:Amines / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002908:Chronic Disease; D003080:Cold Temperature; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D000077206:Gabapentin; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000235:genetics / Q000503:physiopathology; D055959:Intervertebral Disc Degeneration / Q000235:genetics / Q000503:physiopathology; D017116:Low Back Pain / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015676:Osteonectin / Q000235:genetics / Q000502:physiology*; D013314:Stress, Mechanical; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000588:Amines; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D003509:Cyclohexanecarboxylic Acids; D015676:Osteonectin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine; D003907:Dexamethasone