Behavioral signs of chronic back pain in the SPARC-null mouse

Spine (Phila Pa 1976). 2011 Jan 15;36(2):95-102. doi: 10.1097/BRS.0b013e3181cd9d75.

Abstract

Study design: 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.

Summary of background data: 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Amines / pharmacology
  • Analgesics / pharmacology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Chronic Disease
  • Cold Temperature
  • Cyclohexanecarboxylic Acids / pharmacology
  • Dexamethasone / pharmacology
  • Female
  • Gabapentin
  • Hot Temperature
  • Humans
  • Hyperalgesia / genetics
  • Hyperalgesia / physiopathology
  • Intervertebral Disc Degeneration / genetics
  • Intervertebral Disc Degeneration / physiopathology
  • Low Back Pain / genetics
  • Low Back Pain / physiopathology*
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Morphine / pharmacology
  • Motor Activity / drug effects
  • Motor Activity / genetics
  • Motor Activity / physiology
  • Osteonectin / genetics
  • Osteonectin / physiology*
  • Stress, Mechanical
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Amines
  • Analgesics
  • Anti-Inflammatory Agents
  • Cyclohexanecarboxylic Acids
  • Osteonectin
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Morphine
  • Dexamethasone