Lumbar intervertebral disc degeneration associated with axial and radiating low back pain in ageing SPARC-null mice

Abstract

Chronic low back pain (LBP) is a complex, multifactorial disorder with unclear underlying mechanisms. In humans and rodents, decreased expression of secreted protein acidic rich in cysteine (SPARC) is associated with intervertebral disc (IVD) degeneration and signs of LBP. The current study investigates the hypothesis that IVD degeneration is a risk factor for chronic LBP. SPARC-null and age-matched control mice ranging from 6 to 78 weeks of age were evaluated in this study. X-ray and histologic analysis revealed reduced IVD height, increased wedging, and signs of degeneration (bulging and herniation). Cutaneous sensitivity to cold, heat, and mechanical stimuli were used as measures of referred (low back and tail) and radiating pain (hind paw). Region specificity was assessed by measuring icilin- and capsaicin-evoked behaviour after subcutaneous injection into the hind paw or upper lip. Axial discomfort was measured by the tail suspension and grip force assays. Motor impairment was determined by the accelerating rotarod. Physical function was evaluated by voluntary activity after axial strain or during ambulation with forced lateral flexion. SPARC-null mice developed (1) region-specific, age-dependent hypersensitivity to cold, icilin, and capsaicin (hind paw only), (2) axial discomfort, (3) motor impairment, and (4) reduced physical function. Morphine (6 mg/kg, i.p.) reduced cutaneous sensitivity and alleviated axial discomfort in SPARC-null mice. Ageing SPARC-null mice mirror many aspects of the complex and challenging nature of LBP in humans and incorporate both anatomic and functional components of the disease. The current study supports the hypothesis that IVD degeneration is a risk factor for chronic LBP.