Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
Front Immunol. 2023 Feb 9;14:1077088. doi: 10.3389/fimmu.2023.1077088. eCollection 2023.
Accumulating evidence has demonstrated that an association between chronic pain and autoimmune diseases (AIDs). Nevertheless, it is unclear whether these associations refer to a causal relationship. We used a two-sample Mendelian randomization (MR) method to determine the causal relationship between chronic pain and AIDs.
We assessed genome-wide association study (GWAS) summary statistics for chronic pain [multisite chronic pain (MCP) and chronic widespread pain (CWP)], and eight common AIDs, namely, amyotrophic lateral sclerosis (ALS), celiac disease (CeD), inflammatory bowel disease (IBD), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), type 1 diabetes (T1D) and psoriasis. Summary statistics data were from publicly available and relatively large-scale GWAS meta-analyses to date. The two-sample MR analyses were first performed to identify the causal effect of chronic pain on AIDs. The two-step MR and multivariable MR were used to determine if mediators (BMI and smoking) causally mediated any connection and to estimate the proportion of the association mediated by these factors combined.
With the utilization of MR analysis, multisite chronic pain was associated with a higher risk of MS [odds ratio (OR) = 1.59, 95% confidence interval (CI) = 1.01-2.49, = 0.044] and RA (OR = 1.72, 95% CI = 1.06-2.77, = 0.028). However, multisite chronic pain had no significant effect on ALS (OR = 1.26, 95% CI = 0.92-1.71, = 0.150), CeD (OR = 0.24, 95% CI = 0.02-3.64, = 0.303), IBD (OR = 0.46, 95% CI = 0.09-2.27, = 0.338), SLE (OR = 1.78, 95% CI = 0.82-3.88, = 0.144), T1D (OR = 1.15, 95% CI = 0.65-2.02, = 0.627) or Psoriasis (OR = 1.59, 95% CI = 0.22-11.26, = 0.644). We also found positive causal effects of MCP on BMI and causal effects of BMI on MS and RA. Moreover, there were no causal connections between genetically predicted chronic widespread pain and the risk of most types of AIDs disease.
Our MR analysis implied a causal relationship between MCP and MS/RA, and the effect of MCP on MS and RA may be partially mediated by BMI.
越来越多的证据表明，慢性疼痛与自身免疫性疾病（AIDs）之间存在关联。然而，目前尚不清楚这些关联是否指的是因果关系。我们使用两样本孟德尔随机化（MR）方法来确定慢性疼痛与 AIDs 之间的因果关系。
我们评估了慢性疼痛[多部位慢性疼痛（MCP）和慢性广泛性疼痛（CWP）]和八种常见 AIDs（肌萎缩侧索硬化症（ALS）、乳糜泻（CeD）、炎症性肠病（IBD）、多发性硬化症（MS）、类风湿关节炎（RA）、系统性红斑狼疮（SLE）、1 型糖尿病（T1D）和银屑病）的全基因组关联研究（GWAS）汇总统计数据。汇总统计数据来自目前公开的和相对较大规模的 GWAS 荟萃分析。首先进行两样本 MR 分析，以确定慢性疼痛对 AIDs 的因果影响。两步 MR 和多变量 MR 用于确定中介物（BMI 和吸烟）是否会对任何关联产生因果影响，并估计这些因素共同产生的关联比例。
利用 MR 分析，多部位慢性疼痛与 MS 的风险增加相关[比值比（OR）=1.59，95%置信区间（CI）=1.01-2.49， =0.044]和 RA（OR = 1.72，95% CI = 1.06-2.77， = 0.028）。然而，多部位慢性疼痛对 ALS（OR = 1.26，95% CI = 0.92-1.71， = 0.150）、CeD（OR = 0.24，95% CI = 0.02-3.64， = 0.303）、IBD（OR = 0.46，95% CI = 0.09-2.27， = 0.338）、SLE（OR = 1.78，95% CI = 0.82-3.88， = 0.144）、T1D（OR = 1.15，95% CI = 0.65-2.02， = 0.627）或银屑病（OR = 1.59，95% CI = 0.22-11.26， = 0.644）没有显著影响。我们还发现 MCP 对 BMI 的因果作用呈阳性，以及 BMI 对 MS 和 RA 的因果作用。此外，遗传预测的慢性广泛性疼痛与大多数类型的 AIDs 疾病的风险之间没有因果关系。
我们的 MR 分析表明 MCP 与 MS/RA 之间存在因果关系，MCP 对 MS 和 RA 的影响可能部分由 BMI 介导。
