Low back pain (LBP) is a major medical issue and the primary cause for global disability. One common cause of LBP is osteoarthritis (OA) of the lumbar facet joints. OA involves numerous tissues that can induce pain. In particular, during facet joint OA in humans, the articular capsule thickens in response to mechanical and inflammatory stresses; this thickening is associated with LBP. We have previously reported a novel rat model using external spinal linkage to cause lumbar spinal hypomobility and induce OA the in lower lumbar facet joints (L4/5 and L5/6) that may model the progression of spinal OA in humans. This hypomobility results in significant macroscopic OA changes to the articular cartilage and subchondral bone bilaterally by 8‐weeks post linkage. The onset and progression of articular capsule changes and their relationship with pain behaviors is unexplored in this model. Here we examined if lumbar spinal segmental hypomobility in rats is associated with thickening of the ventral articular capsule (ligamentum flavum, LF) as evidenced by increases in morphometric measurements in the bilateral L5/6 facet joints. We hypothesized that 8 weeks of spinal linkage, a time point of significant facet joint OA, is associated with an increase in articular capsule thickness. We used a histological approach with morphometric analyses based upon previously reported methods to test our hypothesis in linked and time matched control rats. LF thickness measurements were performed on images obtained from a brightfield microscope (10X objective, Leica DMRB, optronics microfire camera) on formalin fixed, decalcified, paraffin embedded, Ehrlich's hematoxylin and light green stained 45 μm thick transverse sections of the bilateral L5/6 facet joints. Morphometric measurements were made (OsiriX Lite software) by drawing a line through the thickest region of the LF, perpendicular to the plane of the ventral LF surface. This morphometric approach demonstrated acceptable reliability (ICC= 0.8656). Statistical analysis was performed using an unpaired t‐test. Compared with control animals (n=4), 8 weeks of hypomobility (n=4) was associated with a significant increase in LF thickness (p<0.05). The articular capsule thickness increased at a time point previously shown to have significant OA changes, which is consistent with facet joint OA and LF thickening in human subjects. Increases in articular capsule thickness are hypothesized to contribute both to the induction or reflect the ongoing pathological processes of OA (e.g., prolonged inflammation and fibrosis). Further work is required to determine the onset, joint location, and mechanisms underlying these capsule changes. These findings suggest that lumbar spine hypomobility induces LF thickening.
Low back pain (LBP) is a primary cause of global disability. The lumbar facet joint is recognized as a clinically relevant pain generator. Pain can occur through the onset and progression of facet joint degeneration consistent with spinal osteoarthritis (OA). OA is now defined as a whole joint disease involving many tissues in addition to the articular cartilage, including the joint capsule. Capsular thickening due to mechanical and inflammatory stress can present clinically as a source of LBP. We have previously examined capsular thickening that occurs during OA, by using a rat model of external spinal linkage to cause lumbar spinal hypomobility and induce degeneration in the lower lumbar facet joints (L4/5 and L5/6). We have shown that this model mimics the location, progression, and histopathological changes of the articular cartilage typically reported in human spinal OA. Additionally, we found that by 8 weeks post linkage this degeneration is associated with significant thickening of the ventral articular capsule (ligamentum flavum, LF) in the cephalad portion of the joint. These articular capsule changes are unexplored at later stages of this model when degeneration is more advanced. Here we used a morphometric approach to examine if spinal hypomobility of the bilateral L4/5 and L5/6 facet joints in rats is associated with LF thickening. We hypothesized that 12 weeks of spinal linkage would be associated with an increase in articular capsule thickness in joint regions undergoing cartilage degeneration. We tested our hypothesis by comparing LF thickness in linked and time matched control rats at 12 weeks post linkage. LF thickness measurements were performed on images obtained from a brightfield microscope (10× objective, Leica DMRB, optronics microfire camera) on formalin fixed, decalcified, paraffin embedded, Ehrlich's hematoxylin and light green stained 45 μm thick sections. Morphometric measurements were made by drawing a line through the thickest region of the LF, perpendicular to the plane of the ventral LF surface. This approach demonstrated acceptable inter‐ and intra‐rater reliability (ICC= 0.94 and 0.99). Twelve weeks of hypomobility was associated with a significant increase in LF thickness (p<0.05) compared with control animals in the cephalad and caudal regions. This agrees with our recent findings that significant degeneration is present in the superior articular process (predominantly cephalad region) and inferior articular process (predominantly caudal region) by week 12. Our findings suggest that advanced cartilage degeneration is associated with LF thickening. These findings require additional study to examine the causes of LF thickening (e.g., prolonged inflammation and fibrosis) to better understand the role of the LF in the pathophysiology of OA and OA induced LBP.Support or Funding InformationNCMIC
Low back pain (LBP) is the leading cause of physical disability worldwide and a substantial socioeconomic burden. Osteoarthritis (OA) of the facet joint is a common source of LBP, however, the relationship between spinal OA and LBP is complex and requires further investigation. We previously reported a spine OA rat model that uses external lumbar spinal linkage to induce hypomobility, leading to significant macroscopic facet joint OA changes. This model may replicate human spinal OA progression and allow mechanistic studies of facet joint OA induced pain. Here we examined the onset and progression of L4/5 and L5/6 facet joint articular cartilage degeneration on the superior articular processes (SAP) following linkage. We hypothesized that spinal linkage would result in an early (1–2 weeks post linkage) thinning of articular cartilage that is progressively greater with longer durations. We used a histological approach based upon previously reported methods to test if spinal linkage is associated with decreases in the ratio of articular cartilage surface length (AS) to total joint surface (JS) length and/or regional articular cartilage surface area in linked and time matched control rats (n=3–4 per group) at 1, 2, 4, and 8 weeks post linkage. Measurements (AS, JS, and area) were performed on brightfield microscopy images (10X objective, Leica DMRB, optronics microfire camera) of sections from the mid‐level of L4/5 and L5/6 facet joints. The tissues were formalin fixed, decalcified, paraffin embedded, sectioned (45 μm thick transverse sections), and stained with Ehrlich's hematoxylin and light green. The JS was divided into 11 equidistant points to define 10 regions from ventral to dorsal and calculate articular cartilage area of each region. Intra‐ and inter‐rater reliability was acceptable for JS (ICC = 0.99, ICC = 0.95), AS (ICC = 0.99, ICC = 0.92), and articular cartilage area (ICC = 0.99, ICC = 0.87). Compared to controls, hypomobility was associated with a significant decrease in the AS/JS ratio (one way ANOVA with Tukey's multiple comparisons, p < 0.05) at 2, 4, and 8 weeks post linkage. Linear regression analysis in 1, 2, 4, and 8 week controls demonstrated no relationship with the AS/JS ratio (r2 = 0.09), while in linked rats longer durations predicted more pronounced decreases in the AS/JS ratio (r2 = 0.84). Descriptive regional analysis supported these findings and revealed that linked rats had reduced cartilage surface area (≥25%) in the ventral‐most (1 medial region) and dorsal‐most (3 lateral regions) regions at week 2 compared with controls. Rats with longer linked durations had greater percentage reductions in cartilage area (≥50%) in the same peripheral regions with additional involvement of adjacent regions and expansion toward the center of the joint stemming mostly from the dorsolateral SAP (dorsal regions with ≥25% reduction: week 4 = 4, week 8 = 5). Our findings suggest that hypomobility results in early (by 2 weeks) and progressive cartilage degeneration in the joint periphery, similar to human facet joint OA. The external spinal linking model creates progressive cartilage loss and may be useful in determining the relationship between OA and pain.
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