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Cytokine and neuropeptide levels are associated with pain relief in patients with chronically painful total knee arthroplasty: a pilot study.

ABSTRACT: BACKGROUND: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). METHODS: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. RESULTS: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-? from baseline to 2-months post-injection (p?

SUBMITTER: Singh JA

PROVIDER: S-EPMC5237514 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Cytokine and neuropeptide levels are associated with pain relief in patients with chronically painful total knee arthroplasty: a pilot study.

Singh Jasvinder A JA Noorbaloochi Siamak S Knutson Keith L KL

BMC musculoskeletal disorders 20170114 1

<h4>Background</h4>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).<h4>Methods</h4>Using data from randomized trial of 6 ...[more]

PMID: 28088207

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Project description:BACKGROUND:The study of localized immune-related factors has proven beneficial for a variety of conditions, and one area of interest in the field of orthopaedics is the impact of implants and localized infections on immune response. Several cytokines have shown increased systemic concentrations (in serum/plasma) in response to implants and infection, but tissue-level cytokines have not been investigated as thoroughly. METHODS:This exploratory study investigated tissue-level cytokines in a cohort of patients (N?=?17) in response to total knee arthroplasty and total knee revision to better understand the immune response to implants and localized infection (e.g., prosthetic joint infection). The overall goal of this study was to provide insight into the localized cytokine response of tissues and identify tissue-level markers specific to inflammation caused by implants vs. inflammation caused by infection. Tissues were collected across several anatomical locations and assayed with a panel of 20 human inflammatory cytokines to understand spatial differences in cytokine levels. RESULTS:In this study, six cytokines were elevated in implanted joints, as compared to native joints: IL-10, IL-12p70, IL-13, IL-17A, IL-4, and TNF-? (p?<?0.05). Seven cytokines showed infection-dependent increases in localized tissues: IL-1?, IL-1?, IL-6, IL-8, MCP-1, MIP-1?, and MIP-1? (p?<?0.05). CONCLUSIONS:This study demonstrated that differences exist in tissue-level cytokines in response to presence of implant, and some cytokines were specifically elevated for infection; these responses may be informative of overall tissue health. These results highlight the utility of investigating localized cytokine concentrations to offer novel insights for total knee arthroplasty and total knee revision procedures, as well as their complications. Ultimately, this information could provide additional, quantitative measurements of tissue to aid clinical decision making and patient treatment options.

Project description:Pain control following painful orthopaedic procedures such as total knee arthroplasty (TKA) is an ongoing challenge, as current pain management techniques often result in under-medication and/or complications. In a study designed to test the effect of the micro-current skin patch (MCT) on pain relief in patients following TKA, we followed 24 patients, randomly divided into two groups, one group receiving MCT plus tramadol hydrochloride (tramadol) for pain relief and a control group receiving only tramadol, for 10 days postoperatively. Tramadol was given intramuscularly in increment doses of 100 mg, as needed, for the duration of the study period. Pain was assessed daily using a visual analogue score (VAS). Other parameters, including the effect of MCT on the dose of tramadol needed for pain relief, the degree of wound healing measured at the end of the follow-up period, category of the wound 10 days postoperatively (1, 2 or 3) and total drain fluid volume, were also assessed. During the 10-day postoperative period there was a progressive decrease in pain in patients of both groups, however the patients of the MCT group showed a consistently lower VAS throughout the observation period, most markedly on those follow-up days with the highest pain scores in patients of the control group. This effect was monitored on the basis of the average dose of tramadol administered per day: 200.0+/-7.0 mg/day in the control group and 63.3+/-15.8 mg/day in the MCT group. Wound healing was better with the application of the MCT patch: grade 1 wounds were observed in 50% of the patients of the MCT group as compared to 8.3% in control group. The total drain volume was lower in patients of the MCT group compared to the controls (1020.8+/-211.6 and 1170.8+/-243.5 ml, respectively). None of the patients indicated that they wished to discontinue MCT therapy. This pilot study shows that MCT therapy led to better pain control with a markedly lower need for tramadol as compared to the control group. This better pain control was accompanied by a better healing of the wound and a lower drain volume.

Project description:ObjectiveTo assess short-term efficacy of single intraarticular botulinum toxin (IA-BoNT/A) injection in patients with chronically painful total knee arthroplasty (TKA) in a randomized, placebo-controlled, triple-blind study.MethodsPatients with chronic TKA pain (pain > 6 on 0-10 scale and > 6 months post-TKA) evaluated in and referred from orthopedic surgery clinics were recruited. The primary outcome, proportion of patients with clinically meaningful decrease of at least 2 points on 0-10 visual analog scale (VAS) for pain, was compared between treatment groups at 2 months using comparison of proportions test and for all efficacy timepoints (2, 3, and 4 months) using generalized estimating equations (GEE). Secondary outcomes of global assessment, function, and quality of life were compared using GEE, duration of pain relief by t-test, and adverse events by chi-square test.ResultsIn total, 54 patients with 60 painful TKA were randomized, with main analyses restricted to one TKA per patient (49 TKA in 49 patients). Mean age was 67 years, 84% were men, and mean duration of TKA pain was 4.5 years. A significantly greater proportion of patients (71%) in the IA-BoNT/A group compared to IA-placebo (35%) achieved clinically meaningful reduction in VAS pain at 2 months (p = 0.028) and at all efficacy timepoints (p = 0.019). Duration of meaningful pain relief was significantly greater after IA-BoNT/A, 39.6 days (SD 50.4) compared to IA-placebo, 15.7 days (SD 22.6; p = 0.045). Statistically significantly better scores were seen in IA-BoNT/A vs IA-placebo for all efficacy timepoints for the following outcomes: "very much improved" on physician global assessment of change (p = 0.003); Western Ontario McMaster Osteoarthritis Index physical function (p = 0.026), stiffness (p = 0.004), and total scores (p = 0.024); and Short-Form 36 pain subscale score (p = 0.049). Number of total and serious adverse events was similar between groups, with no patients in either group with new objective motor or sensory deficits during followup.ConclusionIn this single-center randomized trial, single IA-BoNT/A injection provided clinically meaningful short-term improvements in pain, global assessment, and function in patients with chronic painful TKA. A multicenter trial is needed to confirm these findings.

Dataset Information

Cytokine and neuropeptide levels are associated with pain relief in patients with chronically painful total knee arthroplasty: a pilot study.

Publications

Cytokine and neuropeptide levels are associated with pain relief in patients with chronically painful total knee arthroplasty: a pilot study.

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