title: Cytokine and neuropeptide levels are associated with pain relief in patients with chronically painful total knee arthroplasty: a pilot study.
abstract: 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.
authors.affiliation: Medicine Service, VA Medical Center, 700 19th St S, Birmingham, AL, 35233, USA. Jasvinder.md@gmail.com.|Department of Medicine at School of Medicine, University of Alabama at Birmingham Faculty Office Tower, 805B, 510 20th Street S, Birmingham, AL, 35294, USA. Jasvinder.md@gmail.com.|Division of Epidemiology at School of Public Health, University of Alabama at Birmingham, 1720 Second Ave. South, Birmingham, AL, 35294-0022, USA. Jasvinder.md@gmail.com.|Department of Orthopedic Surgery, Mayo Clinic College of Medicine, 200 1st St SW, Rochester, MN, 55905, USA. Jasvinder.md@gmail.com.
authors.forename: Jasvinder A
authors.initials: JA
authors.lastname: Singh
authors.affiliation: Center for chronic disease Outcomes Research, Minneapolis Veterans Affairs Health are System Center, Minneapolis, MN, 55121, USA.|Department of Medicine, University of Minnesota, 401 East River Parkway, Minneapolis, MN, 55455, USA.
authors.forename: Siamak
authors.initials: S
authors.lastname: Noorbaloochi
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, 200 1st St SW, Rochester, MN, 55905, USA.
authors.forename: Keith L
authors.initials: KL
authors.lastname: Knutson
mesh_terms: D000368:Aged; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D018925:Chemokines / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D010149:Postoperative Pain / Q000097:blood* / Q000209:etiology; D010865:Pilot Projects; D013373:Substance P / Q000097:blood*
chemical_list: D015415:Biomarkers; D018925:Chemokines; D013373:Substance P
keywords: Cytokine; Pain; Primary total knee arthroplasty; Substance P; TKA