ISSLS Prize winner: Increased innervation and sensory nervous system plasticity in a mouse model of low back pain due to intervertebral disc degeneration.
METHODS
Immunohistochemical and behavioral study using the SPARC (secreted protein, acidic, rich in cysteine)-null mouse model of low back pain (LBP) associated with accelerated intervertebral disc (IVD) degeneration.


OBJECTIVE
To determine if behavioral signs of LBP in SPARC-null mice are accompanied by sensory nervous system plasticity.


BACKGROUND
IVD pathology is a significant contributor to chronic LBP. In humans and rodents, decreased expression of SPARC is associated with IVD degeneration. We previously reported that SPARC-null mice exhibit age-dependent behavioral signs of chronic axial LBP and radiating leg pain.


METHODS
SPARC-null and age-matched control young, middle-aged, and old mice (1.5, 6, and 24 mo of age, respectively) were evaluated. Cutaneous hind paw sensitivity to cold, heat, and mechanical stimuli were evaluated as measures of radiating pain. The grip force and tail suspension assays were performed to evaluate axial LBP. Motor impairment was assessed using an accelerating rotarod. IVD innervation was identified by immunohistochemistry targeting the nerve fiber marker PGP9.5 and the sensory neuropeptide calcitonin gene-related peptide (CGRP). Sensory nervous system plasticity was evaluated by quantification of CGRP- and neuropeptide-Y-immunoreactivity (-ir) in dorsal root ganglia neurons and CGRP-ir, GFAP-ir (astrocyte marker), and Iba-1-ir (microglia marker) in the spinal cord.


RESULTS
SPARC-null mice developed hypersensitivity to cold, axial discomfort, age-dependent motor impairment, age-dependent increases in sensory innervation in and around the IVDs, age-dependent upregulation of CGRP and neuropeptide-Y in dorsal root ganglia, and age-dependent upregulation of CGRP, microglia, and astrocytes in the spinal cord dorsal horn.


CONCLUSIONS
Increased innervation of degenerating IVDs by sensory nerve fibers and the neuroplasticity in sensory neurons and spinal cord could contribute to the underlying pathobiology of chronic discogenic LBP.


METHODS
N/A.
*Faculty of Dentistry †Alan Edwards Centre for Research on Pain, and ‡McGill Scoliosis & Spine Research Group, McGill University, Montreal, Quebec, Canada §Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan ¶Departments of Neurology & Neurosurgery ‖Anesthesiology and **Pharmacology & Therapeutics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
Masayuki
M
Miyagi
Magali
M
Millecamps
Alexander T
AT
Danco
Seiji
S
Ohtori
Kazuhisa
K
Takahashi
Laura S
LS
Stone
D000818:Animals; D059350:Chronic Pain / Q000503:physiopathology; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000503:physiopathology; D007403:Intervertebral Disc / Q000294:innervation*; D055959:Intervertebral Disc Degeneration / Q000473:pathology*; D017116:Low Back Pain / Q000503:physiopathology*; D008159:Lumbar Vertebrae / Q000294:innervation*; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009473:Neuronal Plasticity / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000473:pathology