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The Role of Cytokines in Acute and Chronic Postsurgical Pain in Pediatric Patients after Major Musculoskeletal
Vidya Chidambaran1, Qing Duan2, Valentina Pilipenko2
1Department of Anesthesiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Insights
Certain cytokines predict acute postsurgical pain, while others indicate a lower risk for chronic postsurgical pain (CPSP). This research identifies key biomarkers for predicting and managing pain after major surgery in adolescents.
Area of Science:
- Biochemistry
- Immunology
- Surgical Research
Background:
- Acute and chronic postsurgical pain (CPSP) are significant challenges following major surgery in adolescents.
- Predictive biomarkers for pain outcomes are needed to personalize patient care and improve recovery.
Approach:
- This prospective, observational study analyzed 16 cytokines in serial blood samples from 112 adolescents undergoing major surgery.
- Cytokine concentrations were measured before and up to two weeks after surgery.
- Statistical analyses correlated baseline and longitudinal cytokine levels with acute pain and the development of CPSP.
Key Points:
- Higher baseline levels of GM-CSF, IL-1β, IL-2, and IL-12p70 were associated with increased acute postsurgical pain.
- Elevated longitudinal concentrations of GM-CSF, IFNγ, IL-1β, IL-7, and IL-12p70 correlated with greater acute pain.
- Lower baseline IL-8 and lower longitudinal IL-6, IL-8, and IL-13 concentrations were linked to a reduced risk of CPSP.
- Female sex and pectus excavatum surgery were associated with higher odds of CPSP for specific cytokines.
Conclusions:
- Pro-inflammatory cytokines are linked to increased acute postoperative pain.
- Anti-inflammatory cytokines are associated with a lower risk of chronic postsurgical pain.
- Cytokines show potential as predictive and prognostic biomarkers for pain management after major pediatric surgery.
Study Objective:
To determine if baseline cytokines and their changes over postoperative days 0-2 (POD0-2) predict acute and chronic postsurgical pain (CPSP) after major surgery.
Design:
Prospective, observational, longitudinal nested study.
Setting:
University-affiliated quaternary children's hospital.
Patients:
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 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 Results:
Analyses 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.
Conclusion:
We 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.
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