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.

Sex differences in a Murine Model of Complex Regional Pain Syndrome

“…The assay is the measurement of the duration of total behaviors (biting, scratching, licking, and shaking) during the 5 minutes after the local subcutaneous injection of capsaicin (2.5 μg in 5 μL, cat. # MT028, Sigma-Aldrich, MO, USA), or vehicle (0.25% DMSO, 0.25% ethanol, 0.125% Tween-80 in saline), into the plantar surface of the right hind paw (Millecamps, Tajerian, Naso, Sage, & Stone, 2012). Quantification was carried out in real time by a blind observer using a stopwatch.…”

A forward dynamics simulation of human lumbar spine flexion predicting the load sharing of intervertebral discs, ligaments, and muscles

“…Back pain is not understood, yet (Hancock et al 2011;Langevin and Sherman 2007;Waddell 1987), albeit a direct relationship between back pain and biological degeneration has been hypothesised (Millecamps et al 2012), although not been proven true so far. This study aimed at providing a consistent, detailed, and quantitative data set of all mechanical variables that might determine biological degeneration, with the presented model is possible to quantify forces, stresses, strains, and rates thereof, as well as repetitive load profiles acting on structures.…”

miR‑148a inhibits pro‑inflammatory cytokines released by intervertebral disc cells by regulating the p38/MAPK pathway

“…It badly affects human life and causes a serious socioeconomic burden (1)(2)(3)(4). An imbalance between anabolic and catabolic genes expressed by chondrocytes that belong to the nucleus pulposus (NP) result in IDD.…”