Vidya Chidambaran , Qing Duan , Valentina Pilipenko , Susan M. Glynn , Alyssa Sproles , Lisa J. Martin , Michael J. Lacagnina , Christopher D. King , Lili Ding
{"title":"细胞因子在一家四级儿科中心重大肌肉骨骼手术后急性和慢性术后疼痛中的作用。","authors":"Vidya Chidambaran , Qing Duan , Valentina Pilipenko , Susan M. Glynn , Alyssa Sproles , Lisa J. Martin , Michael J. Lacagnina , Christopher D. King , Lili Ding","doi":"10.1016/j.bbi.2024.08.056","DOIUrl":null,"url":null,"abstract":"<div><h3>Study Objective</h3><p>To determine if baseline cytokines/chemokines and their changes over postoperative days 0–2 (POD0-2) predict acute and chronic postsurgical pain (CPSP) after major surgery.</p></div><div><h3>Design</h3><p>Prospective, observational, longitudinal nested study.</p></div><div><h3>Setting</h3><p>University-affiliated quaternary children’s hospital.</p></div><div><h3>Patients</h3><p>Subjects (≥8 years old) with idiopathic scoliosis undergoing spine fusion or pectus excavatum undergoing Nuss procedure.</p></div><div><h3>Measurements</h3><p>Demographics, surgical, psychosocial measures, pain scores, and opioid use over POD0-2 were collected. Cytokine concentrations were analyzed in serial blood samples collected before and up to two weeks after 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) post-surgical pain were analyzed using univariable and multivariable regression analyses with adjustment for covariates and mixed effects models were used to associate longitudinal cytokine concentrations with pain outcomes.</p></div><div><h3>Main Results</h3><p>Analyses included 3,164 repeated measures of 16 cytokines/chemokines 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; <em>p</em> = 0.003), IL-1β (β = 0.84, SE 0.36; <em>p</em> = 0.02), IL-2 (β = 0.78, SE 0.34; <em>p</em> = 0.03), and IL-12 p70 (β = 0.88, SE 0.40; <em>p</em> = 0.03) and longitudinal postoperative elevations in GM-CSF (β = 1.38, SE 0.57; <em>p</em> = 0.03), IFNγ (β = 1.36, SE 0.6; <em>p</em> = 0.03), IL-1β (β = 1.25, SE 0.59; <em>p</em> = 0.03), IL-7 (β = 1.65, SE 0.7; <em>p</em> = 0.02), and IL-12 p70 (β = 1.17, SE 0.58; <em>p</em> = 0.04). In contrast, CPSP was associated with lower baseline concentration of IL-8 (β = -0.39, SE 0.17; <em>p</em> = 0.02), and the risk of developing CPSP was elevated in patients with lower longitudinal postoperative concentrations of IL-6 (β = -0.57, SE 0.26; <em>p</em> = 0.03), IL-8 (β = -0.68, SE 0.24; <em>p</em> = 0.006), and IL-13 (β = -0.48, SE 0.22; <em>p</em> = 0.03). Covariates female (vs. male) sex and surgery type (pectus surgery vs. spine) were associated with higher odds for CPSP in baseline adjusted cytokine-CPSP association models for IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNFα, and IL-8, IL-10, respectively.</p></div><div><h3>Conclusion</h3><p>We identified pro-inflammatory cytokine profiles associated with higher risk of acute postoperative pain. Interestingly, pleiotropic cytokine IL-6, chemokine IL-8 (which promotes neutrophil infiltration and monocyte differentiation), and monocyte-released anti-inflammatory cytokine IL-13, were associated with lower CPSP risk. Our results suggest heterogenous outcomes of cytokine/chemokine signaling that can both promote and protect against post-surgical pain. These may serve as predictive and prognostic biomarkers of pain outcomes following surgery.</p></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8000,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The role of cytokines in acute and chronic postsurgical pain after major musculoskeletal surgeries in a quaternary pediatric center\",\"authors\":\"Vidya Chidambaran , Qing Duan , Valentina Pilipenko , Susan M. Glynn , Alyssa Sproles , Lisa J. Martin , Michael J. Lacagnina , Christopher D. King , Lili Ding\",\"doi\":\"10.1016/j.bbi.2024.08.056\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Study Objective</h3><p>To determine if baseline cytokines/chemokines and their changes over postoperative days 0–2 (POD0-2) predict acute and chronic postsurgical pain (CPSP) after major surgery.</p></div><div><h3>Design</h3><p>Prospective, observational, longitudinal nested study.</p></div><div><h3>Setting</h3><p>University-affiliated quaternary children’s hospital.</p></div><div><h3>Patients</h3><p>Subjects (≥8 years old) with idiopathic scoliosis undergoing spine fusion or pectus excavatum undergoing Nuss procedure.</p></div><div><h3>Measurements</h3><p>Demographics, surgical, psychosocial measures, pain scores, and opioid use over POD0-2 were collected. Cytokine concentrations were analyzed in serial blood samples collected before and up to two weeks after 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) post-surgical pain were analyzed using univariable and multivariable regression analyses with adjustment for covariates and mixed effects models were used to associate longitudinal cytokine concentrations with pain outcomes.</p></div><div><h3>Main Results</h3><p>Analyses included 3,164 repeated measures of 16 cytokines/chemokines 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; <em>p</em> = 0.003), IL-1β (β = 0.84, SE 0.36; <em>p</em> = 0.02), IL-2 (β = 0.78, SE 0.34; <em>p</em> = 0.03), and IL-12 p70 (β = 0.88, SE 0.40; <em>p</em> = 0.03) and longitudinal postoperative elevations in GM-CSF (β = 1.38, SE 0.57; <em>p</em> = 0.03), IFNγ (β = 1.36, SE 0.6; <em>p</em> = 0.03), IL-1β (β = 1.25, SE 0.59; <em>p</em> = 0.03), IL-7 (β = 1.65, SE 0.7; <em>p</em> = 0.02), and IL-12 p70 (β = 1.17, SE 0.58; <em>p</em> = 0.04). In contrast, CPSP was associated with lower baseline concentration of IL-8 (β = -0.39, SE 0.17; <em>p</em> = 0.02), and the risk of developing CPSP was elevated in patients with lower longitudinal postoperative concentrations of IL-6 (β = -0.57, SE 0.26; <em>p</em> = 0.03), IL-8 (β = -0.68, SE 0.24; <em>p</em> = 0.006), and IL-13 (β = -0.48, SE 0.22; <em>p</em> = 0.03). Covariates female (vs. male) sex and surgery type (pectus surgery vs. spine) were associated with higher odds for CPSP in baseline adjusted cytokine-CPSP association models for IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNFα, and IL-8, IL-10, respectively.</p></div><div><h3>Conclusion</h3><p>We identified pro-inflammatory cytokine profiles associated with higher risk of acute postoperative pain. Interestingly, pleiotropic cytokine IL-6, chemokine IL-8 (which promotes neutrophil infiltration and monocyte differentiation), and monocyte-released anti-inflammatory cytokine IL-13, were associated with lower CPSP risk. Our results suggest heterogenous outcomes of cytokine/chemokine signaling that can both promote and protect against post-surgical pain. These may serve as predictive and prognostic biomarkers of pain outcomes following surgery.</p></div>\",\"PeriodicalId\":9199,\"journal\":{\"name\":\"Brain, Behavior, and Immunity\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.8000,\"publicationDate\":\"2024-08-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain, Behavior, and Immunity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0889159124005877\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain, Behavior, and Immunity","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0889159124005877","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
The role of cytokines in acute and chronic postsurgical pain after major musculoskeletal surgeries in a quaternary pediatric center
Study Objective
To determine if baseline cytokines/chemokines and their changes over postoperative days 0–2 (POD0-2) predict acute and chronic postsurgical pain (CPSP) after major surgery.
Subjects (≥8 years old) with idiopathic scoliosis undergoing spine fusion or pectus excavatum undergoing Nuss procedure.
Measurements
Demographics, surgical, psychosocial measures, pain scores, and opioid use over POD0-2 were collected. Cytokine concentrations were analyzed in serial blood samples collected before and up to two weeks after 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) post-surgical pain were analyzed using univariable and multivariable regression analyses with adjustment for covariates and mixed effects models were used to associate longitudinal cytokine concentrations with pain outcomes.
Main Results
Analyses included 3,164 repeated measures of 16 cytokines/chemokines 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 = 0.003), IL-1β (β = 0.84, SE 0.36; p = 0.02), IL-2 (β = 0.78, SE 0.34; p = 0.03), and IL-12 p70 (β = 0.88, SE 0.40; p = 0.03) and longitudinal postoperative elevations in 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), and IL-12 p70 (β = 1.17, SE 0.58; p = 0.04). In contrast, CPSP was associated with lower baseline concentration of IL-8 (β = -0.39, SE 0.17; p = 0.02), 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 = 0.03), IL-8 (β = -0.68, SE 0.24; p = 0.006), and IL-13 (β = -0.48, SE 0.22; p = 0.03). Covariates female (vs. male) sex and surgery type (pectus surgery vs. spine) were associated with higher odds for CPSP in baseline adjusted cytokine-CPSP association models for IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNFα, and IL-8, IL-10, respectively.
Conclusion
We identified pro-inflammatory cytokine profiles associated with higher risk of acute postoperative pain. Interestingly, pleiotropic cytokine IL-6, chemokine IL-8 (which promotes neutrophil infiltration and monocyte differentiation), and monocyte-released anti-inflammatory cytokine IL-13, were associated with lower CPSP risk. Our results suggest heterogenous outcomes of cytokine/chemokine signaling that can both promote and protect against post-surgical pain. These may serve as predictive and prognostic biomarkers of pain outcomes following surgery.
期刊介绍:
Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals.
As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.