The Role of Cytokines in Acute and Chronic Postsurgical Pain in Pediatric Patients after Major Musculoskeletal Surgeries.
The Role of Cytokines in Acute and Chronic Postsurgical Pain in Pediatric Patients after Major Musculoskeletal Surgeries.
复制标题
细胞因子在重大肌肉骨骼手术后儿童患者急性和慢性术后疼痛中的作用。
DOI：
10.1101/2024.03.27.24304974
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Ding,Lili
中科院分区：
文献类型：
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作者：
Chidambaran,Vidya;Duan,Qing;Pilipenko,Valentina;Glynn,SusanM;Sproles,Alyssa;Martin,LisaJ;Lacagnina,MichaelJ;King,ChristopherD;Ding,Lili
研究目的确定基线细胞因子及其在术后0-2天（POD0-2）的变化是否预测大手术后急性和慢性术后疼痛（CPSP）。前瞻性、观察性、纵向巢式研究。学校附属第四儿童医院。特发性脊柱侧凸患者（≥8岁）行脊柱融合术或漏斗胸行Nuss手术。测量方法收集了POD0-2期间的人口统计学、外科、社会心理测量、疼痛评分和阿片类药物使用情况。使用Luminex头阵列分析手术前后（长达两周）收集的一系列血液样本中的细胞因子浓度。在数据准备后，分析术前和术后细胞因子浓度与急性（POD0-2以上中重度疼痛的%时间）和慢性（术后3个月以上疼痛评分>3/10）疼痛的关系。在调整协变量后，进行单因素/多因素回归分析，将基线细胞因子浓度与术后疼痛联系起来，并使用混合效应模型将纵向细胞因子浓度与疼痛结果联系起来。主要结果分析包括来自112名受试者的16种细胞因子的3164项测量（中位年龄15.3岁，IQR为13.5-17.0,54.5%女性，59.8%胸大）。急性术后疼痛与较高的基线GM-CSF浓度（β=0.95, SE 0.31, p= 0.003）、IL-1β (β=0.84, SE 0.36, p= 0.02)、IL-2 （β=0.78, SE 0.34, p= 0.03）和IL-12 p70 （β=0.88, SE 0.40, p= 0.03）以及术后GM-CSF （β=1.38, SE 0.57, p= 0.03）、IFNγ (β=1.36, SE 0.6, p= 0.03)、IL-1β (β=1.25, SE 0.59, p= 0.03)、IL-7 （β=1.65, SE 0.7, p= 0.02）和IL-12 p70 （β=1.17, SE 0.58, p= 0.04）升高相关。相比之下，CPSP与较低的基线IL-8浓度相关（β= - 0.39, SE 0.17, p= 0.02），且术后纵向IL-6 （β= - 0.57, SE 0.26, p= 0.03）、IL-8 （β= - 0.68, SE 0.24, p= 0.006）和IL-13 （β= - 0.48, SE 0.22, p= 0.03）浓度较低的患者发生CPSP的风险升高。此外，女性因IL-2、IL-4、IL-5、IL-6、IL-8、IL-10和tnf - α而患CPSP的几率高于男性，而胸椎手术因IL-8和IL-10而患CPSP的几率高于脊柱手术。结论：我们发现促炎细胞因子与术后急性疼痛增加相关，抗炎细胞因子与CPSP风险降低相关，有可能作为预测和预后的生物标志物。
Study ObjectiveTo determine if baseline cytokines and their changes over postoperative days 0–2 (POD0–2) predict acute and chronic postsurgical pain (CPSP) after major surgery.DesignProspective, observational, longitudinal nested study.SettingUniversity-affiliated quaternary children’s hospital.PatientsSubjects (≥8 years old) with idiopathic scoliosis undergoing spine fusion or pectus excavatum undergoing Nuss procedure.MeasurementsDemographics, surgical, psychosocial measures, pain scores, and opioid use over POD0–2 were collected. Cytokine concentrations were analyzed in serial blood samples collected before and after (up to two weeks) surgery, using Luminex bead arrays. After data preparation, relationships between pre- and post-surgical cytokine concentrations with acute (% time in moderate-severe pain over POD0–2) and chronic (pain score>3/10 beyond 3 months post-surgery) pain were analyzed. After adjusting for covariates, univariate/multivariate regression analyses were conducted to associate baseline cytokine concentrations with postoperative pain, and mixed effects models were used to associate longitudinal cytokine concentrations with pain outcomes.Main ResultsAnalyses included 3,164 measures of 16 cytokines from 112 subjects (median age 15.3, IQR 13.5–17.0, 54.5% female, 59.8% pectus). Acute postsurgical pain was associated with higher baseline concentrations of GM-CSF (β=0.95, SE 0.31; p=.003), IL-1β (β=0.84, SE 0.36; p=.02), IL-2 (β=0.78, SE 0.34; p=.03), and IL-12 p70 (β=0.88, SE 0.40; p=.03) and longitudinal postoperative elevations in GM-CSF (β=1.38, SE 0.57; p=.03), IFNγ (β=1.36, SE 0.6; p=.03), IL-1β (β=1.25, SE 0.59; p=.03), IL-7 (β=1.65, SE 0.7, p=.02), and IL-12 p70 (β=1.17, SE 0.58; p=.04). In contrast, CPSP was associated with lower baseline concentration of IL-8 (β= −0.39, SE 0.17; p=.02), and the risk of developing CPSP was elevated in patients with lower longitudinal postoperative concentrations of IL-6 (β= −0.57, SE 0.26; p=.03), IL-8 (β= −0.68, SE 0.24; p=.006), and IL-13 (β= −0.48, SE 0.22; p=.03). Furthermore, higher odds for CPSP were found for females (vs. males) for IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNFα, and for pectus (vs. spine) surgery for IL-8 and IL-10.ConclusionWe identified pro-inflammatory cytokines associated with increased acute postoperative pain and anti-inflammatory cytokines associated with lower CPSP risk, with potential to serve as predictive and prognostic biomarkers.