Correlations between inflammatory cytokines, muscle damage markers and acute postoperative pain following primary total knee arthroplasty

Hai-Bo Si, Ti-Min Yang, Yi Zeng, Zong-Ke Zhou, Fu-Xing Pei, Yan-Rong Lu, Jing-Qiu Cheng, Bin Shen, Hai-Bo Si, Ti-Min Yang, Yi Zeng, Zong-Ke Zhou, Fu-Xing Pei, Yan-Rong Lu, Jing-Qiu Cheng, Bin Shen

Abstract

Background: Despite the success of total knee arthroplasty (TKA) in reducing knee pain and improving functional disability, the management of acute postoperative pain is still unsatisfactory. This study was aimed to quantitatively analyze the possible correlations between inflammatory cytokines, muscle damage markers and acute postoperative pain following primary TKA.

Methods: Patients scheduled for unilateral primary TKA were consecutively included, the serial changes of the numerical rating scale (NRS) at rest (NRSR) and at walking (NRSW), serum inflammatory cytokines and muscle damage markers were assessed before surgery (T0) and at postoperative day 1, 2, 3 and 5 (T1-T4, respectively); while pain disability questionnaire (PDQ) and synovial fluid inflammatory cytokines were evaluated at T0. The correlations between inflammatory cytokines, muscle damage markers and pain scores were examined, and Bonferroni correction was applied for multiple comparisons.

Results: Ninety six patients were included for serum markers and pain evaluations at T0-T4, while 54 (56.25%) for synovial fluid cytokines at T0. The NRSR at T1 and T2 were positively correlated with preoperative NRSW, while the NRSW at T1 to T4 were positively correlated with preoperative NRSR, NRSW and PDQ (all p < 0.05). The NRSR was positively correlated with serum PGE2, IL-6, and CK at T1; the NRSW was positively correlated with serum CRP at T1, with PGE2 and IL-6 at T1 to T3, with CK at T2 and T4, and with Mb and LDH at T1 to T4 (all p < 0.003). Meanwhile, positive correlations were observed between preoperative NRSW and synovial fluid PGE2, IL-6, IL-8, or TNF-α, as well as between PDQ and PGE2 (all p < 0.003), but no associations between postoperative pain scores and preoperative synovial fluid cytokines was found (all p ≥ 0.003). Additionally, the NRSR at T1 and T2, and NRSW at T1 to T4 were positively correlated with body mass index (all p < 0.05).

Conclusions: Serum inflammatory cytokines and muscle damage markers are positively correlated with acute postoperative pain following primary TKA, and the key cytokines (CRP, PGE2, and IL-6) and markers (Mb, CK and LDH) may serve as the targets for developing novel analgesic strategies.

Keywords: Acute postoperative pain; Body mass index; Inflammatory cytokines; Muscle damage markers; Total knee arthroplasty.

Figures

Fig. 1
Fig. 1
Flow diagram of patients through the phases of the study
Fig. 2
Fig. 2
The serial changes of NRS pain scores after primary total knee arthroplasty (Mean ± 95% confidence intervals). a The serial changes of total NRS at rest and at walking following primary TKA. b, c Comparisons of NRS at rest (b) and at walking (c) among obese, overweight, and normal weight patients. *, the difference between obese and overweight patients was significant, p < 0.05; #, the difference between obese and normal weight patients was significant, p < 0.05; △, the difference between overweight and normal weight patients was significant, p < 0.05
Fig. 3
Fig. 3
The serial changes of serum inflammatory cytokines and muscle damage markers after primary total knee arthroplasty. a, b The serial changes of serum inflammatory cytokines, including erythrocyte sedimentation rate (ESR); C-reactive protein (CRP), prostaglandin E2 (PGE2), interleukin-6 and -8 (IL-6 and IL-8), tumor necrosis factor alpha (TNF-α). c The serial changes of serum muscle damage markers, including myoglobin (Mb), creatinine (Cre), creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate transaminase (AST)

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