Background. MicroRNAs play an essential role in regulating pain processing within a wide range of clinical pain disorders. Objectives. The present study aimed to evaluate the role of circulating miRNAs as biomarkers of lower back pain in older adults. In addition, the correlation between miRNAs and other related cofounders such as muscle function, adiposity, malnutrition, and Ca and vitamin D intake was assessed. Methods. A total of 110 older subjects with an age range of 40–60 years were included in this study. The participants were classified according to a modified Oswestry lower back pain disability questionnaire (OSW) into subjects with minimal LBP (n = 40; LBP score: 0–20%), moderate LBP (n = 35; LBP score: 20–40%), and severe LBP (n = 35; LBP score: 41–60%). RT-PCR and immunoassays were used to study the circulating miRNA profile, vitamin D status, and CRP, IL-6, TNF-α, s-Ca, s-BAP, s-OC, and s-NTX levels. In addition, malnutrition and muscle performance were estimated in all subjects as other factors related to LBP. Results. In this study, normal LBP-OSW cutoff values (8.96 ± 3.6) were reported in 36.4% of the total population, whereas 63.6% of the population had higher LBP-OSW scores, classified as follows: 31.8% with moderate LBP (LBP-OSW score: 31.4 ± 9.1) and 31.8% with severe LBP (LBP-OSW score: 54.9 ± 14.6). Four circulating miRNAs, namely, miR-146a, miR-558, miR-155, and miR-124a, as biomarkers of the intensity of back pain were identified in all participants. In subjects with moderate to severe LBP, the expression levels of miR-146a and miR-558 were significantly reduced and those of miR-155 and miR-124a were significantly increased compared to subjects with minimal LBP scores. Subjects with moderate to severe LBP showed a significant increase in adiposity markers, lower PA, muscle performance, malnutrition, and lower Ca and vitamin D intake compared to normal controls. In addition, serum levels of vitamin D and circulated plasma markers of inflammation and bone metabolism such as CRP, IL-6, TNF-α, s-Ca, s-BAP, s-OC, and s-NTX were significantly reduced in severe LBP cases compared to those with minimal LBP scores. The expressed circulating miRNAs were significantly associated with the measured muscle performance, adiposity, PA score, inflammation, and bone metabolism cofounders in subjects with higher LBP-OSW scores. The expressed miRNAs, along with other LBP cofounders, were significantly associated with ∼63.9–86.4% of the incidence of LBP in older adults. Conclusions. In older adults with vitamin D deficiency, the severity of LBP was significantly associated with the expression of circulating miRNAs, adiposity, bone metabolism, inflammation, and muscle performance. In addition, the expressed miRNAs, along with other LBP cofounders, were significantly associated with ∼63.9–86.4% of the incidence of LBP in older adults. These results suggest the possibility of using microRNAs as therapeutics to alleviate established pain and as biomarkers in old adults with painful conditions.

中文翻译：

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患有下背痛的老年人的维生素 D 缺乏和循环 MicroRNA 的分子变化


背景。 MicroRNA 在调节多种临床疼痛疾病的疼痛处理中发挥着重要作用。目标。本研究旨在评估循环 miRNA 作为老年人腰痛生物标志物的作用。此外，还评估了 miRNA 与其他相关共同因素（如肌肉功能、肥胖、营养不良以及钙和维生素 D 摄入量）之间的相关性。方法。本研究共纳入 110 名年龄在 40-60 岁之间的老年受试者。根据修改后的 Oswestry 腰痛残疾问卷 (OSW)，将参与者分为轻度 LBP 受试者（ n = 40；LBP 评分：0–20%）、中度 LBP 受试者（ n = 35；LBP 评分：20–40%） ）和严重腰痛（ n = 35；腰痛评分：41–60%）。 RT-PCR 和免疫测定用于研究循环 miRNA 谱、维生素 D 状态以及 CRP、IL-6、TNF- α 、s-Ca、s-BAP、s-OC 和 s-NTX 水平。此外，所有受试者的营养不良和肌肉表现都被评估为与 LBP 相关的其他因素。结果。在这项研究中，总人口中 36.4% 的 LBP-OSW 截止值正常（8.96 ± 3.6），而 63.6% 的人口具有较高的 LBP-OSW 分数，分类如下： 31.8% 患有中度 LBP（LBP- OSW 评分：31.4 ± 9.1），重度 LBP 为 31.8%（LBP-OSW 评分：54.9 ± 14.6）。在所有参与者中均鉴定出四种循环 miRNA，即 miR-146a、miR-558、miR-155 和 miR-124a，作为背痛强度的生物标志物。 与腰痛评分最低的受试者相比，中重度腰痛受试者中 miR-146a 和 miR-558 的表达水平显着降低，而 miR-155 和 miR-124a 的表达水平显着升高。与正常对照相比，中度至重度 LBP 受试者的肥胖标志物显着增加、PA 降低、肌肉性能降低、营养不良以及钙和维生素 D 摄入量降低。此外，重症患者的血清维生素 D 水平以及炎症和骨代谢的循环血浆标志物（如 CRP、IL-6、TNF- α 、s-Ca、s-BAP、s-OC 和 s-NTX）显着降低。腰痛病例与腰痛评分最低的病例进行比较。在 LBP-OSW 评分较高的受试者中，表达的循环 miRNA 与测量的肌肉性能、肥胖、PA 评分、炎症和骨代谢共同因素显着相关。表达的 miRNA 以及其他 LBP 共同创始人，与老年人 63.9-86.4% 的 LBP 发病率显着相关。结论。在维生素 D 缺乏的老年人中，LBP 的严重程度与循环 miRNA 的表达、肥胖、骨代谢、炎症和肌肉性能显着相关。此外，表达的 miRNA 以及其他 LBP 共同创始人，与老年人 63.9-86.4% 的 LBP 发病率显着相关。这些结果表明，可以使用 microRNA 作为缓解既定疼痛的疗法，并作为患有疼痛状况的老年人的生物标志物。