Pub Date : 2026-02-01Epub Date: 2025-03-25DOI: 10.1213/ANE.0000000000007504
Nathalie M Malewicz-Oeck, Jana L Aulenkamp, Sebastian Oeck, Claudia Scheffzük, Peter K Zahn, Wiebke Hansen, Alexander Schramm, Christine H Meyer-Frießem
Background: After fracture-related surgery, chronic posttraumatic and/or postsurgical pain (CPSP) has a high incidence rate of up to 43% a year after surgery. Yet the underlying mechanisms are poorly understood. Murine and clinical evidence suggest immunological modulation of postsurgical pain. However, the specific cytokine profiles of patients who develop CPSP after fracture-related surgery remain to be determined. Therefore, we analyzed in an exploratory manner cytokines, chemokines and adipocytokines in patients with and without CPSP up to 1 year after fracture-related surgery.
Methods: A prospective longitudinal serum profiling of 30 patients with traumatic fractures that required osteosynthesis was conducted on the first day (D1), at 6 weeks (W6) and 1 year after surgery (Y1). Patients with CPSP at Y1 were compared to those who did not develop CPSP. A total of 22 pro- and anti-inflammatory serum cytokines, including adipocytokines, were quantified using Luminex technology. Statistical analyses included χ² test, t test, and Mann-Whitney U test, Spearman's rank correlations, and repeated-measures mixed models with Bonferroni correction for cytokine differences between patients with and without CPSP. Receiver-operating characteristic (ROC) curves evaluated the discriminatory ability of specific cytokines regarding the development of CPSP.
Results: Patients with CPSP 1 year after surgery (n = 12/30, 40%) exhibited elevated resistin levels at Y1 (CPSP: 1.04 ± 1.04 vs no-CPSP: 0.41 ± 0.31 pg/mL; P < .001) as well as higher adiponectin levels at Y1 (CPSP: 9.37 ± 8.23 vs no-CPSP: 5.57 ± 2.75 μg/mL; P = .008). Patients with CPSP had higher Rantes/CCL5 (CC-chemokine ligand 5) levels immediately after surgery on D1 than patients without CPSP (mean difference [MD] = 5.5, confidence interval [CI], 1.7-9.3 ng/mL; P = .014). At W6 and Y1, adiponectin and CCL5 levels correlated with pain intensity in patients with CPSP (adiponectin: r = 0.50, P = .03; CCL5: r = -0.50, P = .03). Across the entire patient population, resistin levels were correlated with pain intensity (r = 0.34, P < .001; D1-Y1).
Conclusions: Our explorative cytokine analysis uncovered an imbalance in serum cytokines and chemokines during the chronification process in patients who developed CPSP 1 year after surgically treated fractures. In particular, adiponectin and resistin were noted to be novel biomarkers for CPSP development. These data provide preliminary insight into a potential unexplored crosstalk between chronic postoperative pain and adipocytokines in the chronification of CPSP, which remains to be further analyzed.
背景：骨折相关手术后，慢性创伤后和/或术后疼痛（CPSP）的发生率高达43%。然而，人们对其潜在机制知之甚少。小鼠和临床证据表明免疫调节术后疼痛。然而，骨折相关手术后发生CPSP患者的特异性细胞因子谱仍有待确定。因此，我们以探索性的方式分析了骨折相关手术后1年内伴有和未伴有CPSP患者的细胞因子、趋化因子和脂肪细胞因子。方法：对30例需要植骨的外伤性骨折患者在术后第一天（D1）、6周（W6）和1年（Y1）进行前瞻性纵向血清分析。将1岁时发生CPSP的患者与未发生CPSP的患者进行比较。采用Luminex技术对22种促炎和抗炎血清细胞因子（包括脂肪细胞因子）进行定量分析。统计分析包括χ 2检验、t检验、Mann-Whitney U检验、Spearman秩相关、重复测量混合模型和Bonferroni校正的细胞因子在有和没有CPSP患者之间的差异。受试者工作特征（ROC）曲线评估特定细胞因子对CPSP发展的区分能力。结果：CPSP患者术后1年（n = 12/ 30,40 %）抵抗素水平在Y1时升高(CPSP: 1.04±1.04 vs无CPSP: 0.41±0.31 pg/mL；P < 0.001)以及Y1时较高的脂联素水平(CPSP: 9.37±8.23 vs no-CPSP: 5.57±2.75 μg/mL；P = .008)。CPSP患者术后D1即刻Rantes/CCL5 （cc趋化因子配体5）水平高于非CPSP患者(平均差异[MD] = 5.5，置信区间[CI]， 1.7-9.3 ng/mL；P = .014)。在W6和Y1时，脂联素和CCL5水平与CPSP患者疼痛强度相关(脂联素：r = 0.50, P = 0.03；CCL5: r = -0.50, P = .03)。在整个患者群体中，抵抗素水平与疼痛强度相关(r = 0.34, P < 0.001；D1-Y1)。结论：我们的探索性细胞因子分析发现，在骨折术后1年发生CPSP的患者的慢性化过程中，血清细胞因子和趋化因子存在失衡。特别是，脂联素和抵抗素被认为是CPSP发展的新生物标志物。这些数据为慢性术后疼痛和脂肪细胞因子在CPSP的慢性化过程中潜在的未被探索的相互作用提供了初步的见解，这仍有待进一步分析。
{"title":"The Relationship Between Chronic Postoperative Pain and Circulating Inflammatory Biomarkers (CC-Chemokine Ligand 5, Adiponectin, and Resistin) After Fracture-Related Surgery in Pain Chronification.","authors":"Nathalie M Malewicz-Oeck, Jana L Aulenkamp, Sebastian Oeck, Claudia Scheffzük, Peter K Zahn, Wiebke Hansen, Alexander Schramm, Christine H Meyer-Frießem","doi":"10.1213/ANE.0000000000007504","DOIUrl":"10.1213/ANE.0000000000007504","url":null,"abstract":"<p><strong>Background: </strong>After fracture-related surgery, chronic posttraumatic and/or postsurgical pain (CPSP) has a high incidence rate of up to 43% a year after surgery. Yet the underlying mechanisms are poorly understood. Murine and clinical evidence suggest immunological modulation of postsurgical pain. However, the specific cytokine profiles of patients who develop CPSP after fracture-related surgery remain to be determined. Therefore, we analyzed in an exploratory manner cytokines, chemokines and adipocytokines in patients with and without CPSP up to 1 year after fracture-related surgery.</p><p><strong>Methods: </strong>A prospective longitudinal serum profiling of 30 patients with traumatic fractures that required osteosynthesis was conducted on the first day (D1), at 6 weeks (W6) and 1 year after surgery (Y1). Patients with CPSP at Y1 were compared to those who did not develop CPSP. A total of 22 pro- and anti-inflammatory serum cytokines, including adipocytokines, were quantified using Luminex technology. Statistical analyses included χ² test, t test, and Mann-Whitney U test, Spearman's rank correlations, and repeated-measures mixed models with Bonferroni correction for cytokine differences between patients with and without CPSP. Receiver-operating characteristic (ROC) curves evaluated the discriminatory ability of specific cytokines regarding the development of CPSP.</p><p><strong>Results: </strong>Patients with CPSP 1 year after surgery (n = 12/30, 40%) exhibited elevated resistin levels at Y1 (CPSP: 1.04 ± 1.04 vs no-CPSP: 0.41 ± 0.31 pg/mL; P < .001) as well as higher adiponectin levels at Y1 (CPSP: 9.37 ± 8.23 vs no-CPSP: 5.57 ± 2.75 μg/mL; P = .008). Patients with CPSP had higher Rantes/CCL5 (CC-chemokine ligand 5) levels immediately after surgery on D1 than patients without CPSP (mean difference [MD] = 5.5, confidence interval [CI], 1.7-9.3 ng/mL; P = .014). At W6 and Y1, adiponectin and CCL5 levels correlated with pain intensity in patients with CPSP (adiponectin: r = 0.50, P = .03; CCL5: r = -0.50, P = .03). Across the entire patient population, resistin levels were correlated with pain intensity (r = 0.34, P < .001; D1-Y1).</p><p><strong>Conclusions: </strong>Our explorative cytokine analysis uncovered an imbalance in serum cytokines and chemokines during the chronification process in patients who developed CPSP 1 year after surgically treated fractures. In particular, adiponectin and resistin were noted to be novel biomarkers for CPSP development. These data provide preliminary insight into a potential unexplored crosstalk between chronic postoperative pain and adipocytokines in the chronification of CPSP, which remains to be further analyzed.</p>","PeriodicalId":7784,"journal":{"name":"Anesthesia and analgesia","volume":" ","pages":"373-383"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-25DOI: 10.1213/ANE.0000000000007812
Natalie R Bennion, Thomas S Brower, Craig R Ballard, Jacob Steenblik, Ki Hwa Lee, Talmage D Egan, Jeffrey D Swenson, Nathan L Pace, Ken B Johnson
{"title":"In Response.","authors":"Natalie R Bennion, Thomas S Brower, Craig R Ballard, Jacob Steenblik, Ki Hwa Lee, Talmage D Egan, Jeffrey D Swenson, Nathan L Pace, Ken B Johnson","doi":"10.1213/ANE.0000000000007812","DOIUrl":"10.1213/ANE.0000000000007812","url":null,"abstract":"","PeriodicalId":7784,"journal":{"name":"Anesthesia and analgesia","volume":" ","pages":"e13-e15"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-21DOI: 10.1213/ANE.0000000000007862
Megan M Talbot, Srikiran Ramarapu, Amir L Butt, Aimee Pak
{"title":"Cost-Risk-Benefit Analysis of Methadone Use in Cardiothoracic Surgery.","authors":"Megan M Talbot, Srikiran Ramarapu, Amir L Butt, Aimee Pak","doi":"10.1213/ANE.0000000000007862","DOIUrl":"10.1213/ANE.0000000000007862","url":null,"abstract":"","PeriodicalId":7784,"journal":{"name":"Anesthesia and analgesia","volume":" ","pages":"e30-e31"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145595554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-07DOI: 10.1213/ANE.0000000000007835
Alexander Pastino
{"title":"An Argument Against Centimeters of Water.","authors":"Alexander Pastino","doi":"10.1213/ANE.0000000000007835","DOIUrl":"10.1213/ANE.0000000000007835","url":null,"abstract":"","PeriodicalId":7784,"journal":{"name":"Anesthesia and analgesia","volume":" ","pages":"e19-e20"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-07DOI: 10.1213/ANE.0000000000007836
Jaideep J Pandit
{"title":"Units of Measurement of Vascular and Gas Pressures: Journal Response.","authors":"Jaideep J Pandit","doi":"10.1213/ANE.0000000000007836","DOIUrl":"10.1213/ANE.0000000000007836","url":null,"abstract":"","PeriodicalId":7784,"journal":{"name":"Anesthesia and analgesia","volume":" ","pages":"e20-e21"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-08-29DOI: 10.1213/ANE.0000000000007702
Martin Dupuis, Alexia Bacci, Anaïs Adolle, Dimitri Sourd, Antoine Vilotitch, Pierre Bouzat
{"title":"Regional Analgesia Through Posterior Quadratus Lumborum Block in Laparoscopic and Robot-Assisted Nephrectomies: A Retrospective Observational Study.","authors":"Martin Dupuis, Alexia Bacci, Anaïs Adolle, Dimitri Sourd, Antoine Vilotitch, Pierre Bouzat","doi":"10.1213/ANE.0000000000007702","DOIUrl":"10.1213/ANE.0000000000007702","url":null,"abstract":"","PeriodicalId":7784,"journal":{"name":"Anesthesia and analgesia","volume":" ","pages":"425-428"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12753117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-24DOI: 10.1213/ANE.0000000000007849
Frank R Major, Trevor A Pickering, Jeffry T Nahmias, Catherine M Kuza
{"title":"In Response.","authors":"Frank R Major, Trevor A Pickering, Jeffry T Nahmias, Catherine M Kuza","doi":"10.1213/ANE.0000000000007849","DOIUrl":"10.1213/ANE.0000000000007849","url":null,"abstract":"","PeriodicalId":7784,"journal":{"name":"Anesthesia and analgesia","volume":" ","pages":"e27-e28"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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