Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, 515 East 71st St., New York, NY, 10021, USA.
Department of Cell and Developmental Biology, Weill Cornell Medicine, Graduate School of Medical Science, New York, NY, 10065, USA.
Eur Spine J. 2023 Mar;32(3):848-858. doi: 10.1007/s00586-023-07545-3. Epub 2023 Jan 31.
Aging is a risk factor for several debilitating conditions including those related to chronic back pain and intervertebral disc degeneration, both of which have no cure. Mouse models are useful tools for studying disc degeneration and chronic back pain in a tightly controlled and clinically relevant aging environment. Moreover, mice offer the advantage of carrying out longitudinal studies to understand the etiology and progression of disc pathology induced by genetic or surgical strategies. Previously, age-related behavioral trends of discomfort and enhanced nociception in mice were reported; however, whether these measures are mediated by structural and pathological changes in the disc is unknown.
The goal of the present observational study was to identify behavioral correlates of age-related degenerative changes in the disc. Towards this, we collected radiographs from 150 mice (77 females) between three and 23 months of age and measured the disc height index for each level of lumbar disc. Behavioral measures were collected on several of these mice which included rearing and distance travelled in an open field test; time spent in rearing, reaching, immobile, and self-suspended in the tail suspension test; bilateral hind paw licking in response to cold allodynia using acetone; and unilateral hind paw licking in response to heat hyperalgesia using capsaicin.
Results show that the lower lumbar discs lose height with age and these changes are independent of body composition measures including body weight, bone mineral density, fat mass, lean weight mass, percent fat mass, and percent lean mass. Disc height positively correlates with rearing and mobility in the open field test, immobility in the tail suspension test, and thermal hyperalgesia. Disc height negatively correlates with cold allodynia and rearing in the tail suspension test. Furthermore, mediation analysis shows that the lumbosacral disc significantly mediates the effect of age on rearing in the open field test, but not cold allodynia, suggesting this behavior is a useful measure of age-related axial discomfort due to disc degeneration.
In summary, the findings from the current study show that disc height are associated with measures of axial discomfort and nociception in mice.
衰老会增加多种使人虚弱的疾病的发病风险，包括与慢性腰痛和椎间盘退行性变相关的疾病，这两种疾病目前都无法治愈。在严格控制和具有临床相关性的衰老环境中，研究椎间盘退行性变和慢性腰痛，小鼠模型是非常有用的工具。此外，小鼠还具有开展纵向研究的优势，可用于了解遗传或手术策略引起的椎间盘病理的病因和进展。此前有研究报道了小鼠与年龄相关的不适和痛觉过敏行为趋势，但这些措施是否受椎间盘结构和病理变化的影响尚不清楚。
本观察性研究的目的是确定与椎间盘退行性改变相关的年龄相关行为变化的相关性。为此，我们收集了 150 只（77 只雌性）年龄在 3 至 23 个月之间的小鼠的 X 光片，并测量了每节腰椎间盘的椎间盘高度指数。对其中一些小鼠进行了行为测量，包括在旷场试验中直立和移动的距离；在尾部悬挂试验中直立、达到、不动和自我悬挂的时间；用丙酮引起冷感觉过敏时双侧后爪舔舐；用辣椒素引起热痛觉过敏时单侧后爪舔舐。
结果表明，较低的腰椎间盘随年龄增长而降低高度，这些变化与包括体重、骨密度、脂肪量、瘦体重、脂肪百分比和瘦体重百分比在内的身体成分测量值无关。椎间盘高度与旷场试验中的直立和活动、尾部悬挂试验中的不动以及热痛觉过敏呈正相关。椎间盘高度与冷感觉过敏和尾部悬挂试验中的直立呈负相关。此外，中介分析表明，腰骶椎间盘显著介导了年龄对旷场试验中直立的影响，但不介导冷感觉过敏，这表明这种行为是评估与椎间盘退行性变相关的轴向不适的有用指标。
总之，本研究结果表明，椎间盘高度与小鼠的轴向不适和痛觉过敏测量值有关。
