Singh Jasvinder A, Noorbaloochi Siamak, Knutson Keith L
Medicine Service, VA Medical Center, 700 19th St S, Birmingham, AL, 35233, USA.
Department of Medicine at School of Medicine, University of Alabama at Birmingham Faculty Office Tower, 805B, 510 20th Street S, Birmingham, AL, 35294, USA.
BMC Musculoskelet Disord. 2017 Jan 14;18(1):17. doi: 10.1186/s12891-016-1375-2.
There are few studies with an assessment of the levels of cytokines or neuropeptides as correlates of pain and pain relief in patients with painful joint diseases. Our objective was to assess whether improvements from baseline to 2-months in serum cytokine, chemokine and substance P levels were associated with clinically meaningful pain relief at 2-months post-injection in patients with painful total knee arthroplasty (TKA).
Using data from randomized trial of 60 TKAs, we assessed the association of change in cytokine/chemokine/Substance P levels with primary study outcome, clinically important improvement in Western Ontario McMaster Osteoarthritis Index (WOMAC) pain subscale at 2-months post-injection using Student's t-tests and Spearman's correlation coefficient (non-parametric). Patients were categorized as pain responders (20-point reduction or more on 0-100 WOMAC pain) vs. pain non-responders. Sensitivity analysis used 0-10 daytime pain numeric rating scale (NRS) instead of WOMAC pain subscale.
In a pilot study, compared to non-responders (n = 23) on WOMAC pain scale at 2-months, pain responders (n = 12) had significantly greater increase in serum levels of IL-7, IL-10, IL-12, eotaxin, interferon gamma and TNF-α from baseline to 2-months post-injection (p < 0.05 for all). Change in several cytokine/chemokine and substance P levels from pre-injection to 2-month follow-up correlated significantly with change in WOMAC pain with correlation coefficients ranging -0.37 to -0.51: IL-2, IL-7, IL-8, IL-9, IL-16, IL-12p, GCSF, IFN gamma, IP-10, MCP, MIP1b, TNF-α and VEGF (n = 35). Sensitivity analysis showed that substance P decreased significantly more from baseline to 2-months in the pain responders (0.54 ± 0.53; n = 10) than in the pain non-responders (0.48 ± 1.18; n = 9; p = 0.023) and that this change in serum substance P correlated significantly with change in daytime NRS pain, correlation coefficient was 0.53 (p = 0.021; n = 19). Findings should be interpreted with caution, since cytokine analyses were performed for a sub-group of the entire trial population.
Serum cytokine, chemokine and Substance P levels correlated with pain response in patients with painful TKA after an intra-articular injection in a randomized trial.
很少有研究评估细胞因子或神经肽水平与疼痛性关节疾病患者疼痛及疼痛缓解之间的关联。我们的目的是评估在疼痛性全膝关节置换术（TKA）患者中，从基线到2个月时血清细胞因子、趋化因子和P物质水平的改善是否与注射后2个月时具有临床意义的疼痛缓解相关。
利用60例TKA随机试验的数据，我们使用学生t检验和Spearman相关系数（非参数）评估细胞因子/趋化因子/P物质水平的变化与主要研究结局（注射后2个月时西安大略和麦克马斯特大学骨关节炎指数（WOMAC）疼痛亚量表的临床重要改善）之间的关联。患者被分为疼痛缓解者（WOMAC疼痛评分从0 - 100分降低20分或更多）和疼痛未缓解者。敏感性分析使用0 - 10分的日间疼痛数字评定量表（NRS）代替WOMAC疼痛亚量表。
在一项初步研究中，与2个月时WOMAC疼痛量表上的未缓解者（n = 23）相比，疼痛缓解者（n = 12）从基线到注射后2个月血清IL-7、IL-10、IL-12、嗜酸性粒细胞趋化蛋白、干扰素γ和TNF-α水平的升高显著更大（所有p < 0.05）。从注射前到2个月随访时，几种细胞因子/趋化因子和P物质水平的变化与WOMAC疼痛的变化显著相关，相关系数范围为 -0.37至 -0.51：IL-2、IL-7、IL-8、IL-9、IL-16、IL-12p、GCSF、IFNγ、IP-10、MCP、MIP1b、TNF-α和VEGF（n = 35）。敏感性分析表明，疼痛缓解者（0.54 ± 0.53；n = 10）从基线到2个月时P物质的下降显著大于疼痛未缓解者（0.48 ± 1.18；n = 9；p = 0.023），并且血清P物质的这种变化与日间NRS疼痛的变化显著相关，相关系数为0.53（p = 0.021；n = 19）。由于细胞因子分析是对整个试验人群的一个亚组进行的，因此研究结果应谨慎解读。
在一项随机试验中，关节内注射后，疼痛性TKA患者的血清细胞因子、趋化因子和P物质水平与疼痛反应相关。
