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Preoperative serum circulating microRNAs as potential biomarkers for chronic postoperative pain after total knee replacement.

ABSTRACT: BACKGROUND:Chronic postoperative pain affects approximately 20% of patients with knee osteoarthritis after total knee replacement. Circulating microRNAs can be found in serum and might act as biomarkers in a variety of diseases. The current study aimed to investigate the preoperative expression of circulating microRNAs as potential predictive biomarkers for the development of chronic postoperative pain in the year following total knee replacement. METHODS:Serum samples, collected preoperatively from 136 knee osteoarthritis patients, were analyzed for 21 circulatory microRNAs. Pain intensity was assessed using a visual analog scale before and one year after total knee replacement. Patients were divided into a low-pain relief group (pain relief percentage <30%) and a high-pain relief group (pain relief percentage >30%) based on their pain relief one year after total knee replacement, and differences in microRNAs expression were analyzed between the two groups. RESULTS:We found that three microRNAs were preoperatively dysregulated in serum in the low-pain relief group compared with the high-pain relief group. MicroRNAs hsa-miR-146a-5p, -145-5p, and -130?b-3p exhibited fold changes of 1.50, 1.55, and 1.61, respectively, between the groups (all P values?

SUBMITTER: Giordano R

PROVIDER: S-EPMC7543153 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Preoperative serum circulating microRNAs as potential biomarkers for chronic postoperative pain after total knee replacement.

Giordano Rocco R Petersen Kristian Kjær KK Andersen Hjalte Holm HH Lichota Jacek J Valeriani Massimiliano M Simonsen Ole O Arendt-Nielsen Lars L

Molecular pain 20200101

<h4>Background</h4>Chronic postoperative pain affects approximately 20% of patients with knee osteoarthritis after total knee replacement. Circulating microRNAs can be found in serum and might act as biomarkers in a variety of diseases. The current study aimed to investigate the preoperative expression of circulating microRNAs as potential predictive biomarkers for the development of chronic postoperative pain in the year following total knee replacement.<h4>Methods</h4>Serum samples, collected ...[more]

PMID: 33021154

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Project description:ObjectiveTo examine impact of pre-existing and incident problematic musculoskeletal (MSK) areas after total knee replacement (TKR) on postoperative 60-month Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain/function scores.MethodsUsing data from a randomized controlled trial of subjects undergoing TKR for osteoarthritis, we assessed problematic MSK areas in six body regions before TKR and 12, 24, 36, and 48 months after TKR. We defined the following two variables: 1) density count (number of problematic MSK areas occurring after TKR; range 0-24) and 2) cumulative density count (problematic MSK areas both before and after TKR, categorized into four levels: no preoperative areas and density count of 0-1 [reference group]; no preoperative areas and density count of 2 or more; one or more preoperative areas and density count of 0-1; and one or more preoperative areas and density count of 2 or greater). We evaluated the associations between categorized 60-month WOMAC and cumulative density count by ordinal logistic regression.ResultsAmong 230 subjects, 24% reported one or more preoperative problematic MSK area. After TKR, 75% reported a density count of 0 to 1; 25% reported a density count of 2 or more. Compared with the reference group, each cumulative density count category was associated with an increased odds of having a higher category of 60-month WOMAC pain score, as follows: 2.97 (95% confidence interval [CI], 1.48-5.98) for no preoperative problematic areas and density count of 2 or greater, 3.31 (95% CI, 1.64-6.66) for one or more preoperative problematic areas and density count of 0 to 1, and 2.85 (95% CI, 0.97-8.39) for one or more preoperative problematic areas and density count of 2 or greater. Similar associations were observed with 60-month WOMAC function score.ConclusionIn TKR recipients, the presence of problematic musculoskeletal areas beyond the index knee-preoperatively and/or postoperatively-was associated with worse 60-month WOMAC pain/function score.

Project description:Pain is the main impetus for osteoarthritis (OA) patients to seek healthcare including joint replacement. The pain experience in OA is heterogeneous and affected by factors across multiple domains-peripheral, psychological, and neurological. This indicates the existence of homogenous subgroups/phenotypes within OA patients with pain. We recently identified three pain phenotypes using a wide spectrum of pain-related factors, including structural damage on magnetic resonance imaging (MRI), emotional problems, number of painful sites, sex, body mass index, education level and comorbidities (i.e., Class 1: high prevalence of emotional problems and low prevalence of structural damage (25%); Class 2: low prevalence of emotional problems and high prevalence of structural damage (20%); Class 3: low prevalence of emotional problems and low prevalence of structural damage (55%)). This study was to examine whether the total knee replacement (TKR) risk over 12 years was different among these three pain phenotypes. Data on 963 participants (mean age 62.8 ± 7.4 years) from a population-based cohort study were utilised. Data on socio-demographic, psychological and comorbidities were collected. MRI of the right knee structural pathology was performed. TKR history was ascertained by linking to the Australian Orthopedic Association National Joint Replacement Registry. Latent class analysis and the Cox proportional hazards model were applied for the analysis. During the follow-up period, 41 right and 44 left TKRs in 67 participants were identified. In multivariable analyses, participants in Class 1 and 2 had a higher risk of having a TKR (Class 1 vs. Class 3, HR (hazard ratio) 4.81, 95%CI (confidence interval) 2.33-9.93; Class 2 vs. Class 3, HR 9.23, 95%CI 4.66-18.30). These associations were stronger in the imaged right knee but were also significant in the left knee. Participants within distinct pain phenotypes have different risks of TKR, suggesting that the identified phenotypes reflect distinct clinical subgroups with different prognoses. The risk for TKR was higher in Class 1 than that in Class 3, suggesting that pain/emotional status is a stronger driver for TKR than structural damage, and that selecting patients for TKR needs to be optimized in clinical practice.

Project description:ObjectivesA key predictor for developing chronic residual pain after total knee or hip arthroplasty (TKA/THA) is sensitisation. Sensitisation can be defined as an 'increased responsiveness of nociceptive neurons in the nervous system'. Aim of this study is to investigate the effects of preoperative treatment with duloxetine in sensitised knee and hip osteoarthritis (OA) patients on postoperative chronic residual pain up to 1 year after arthroplasty.SettingA multicentre, pragmatic, prospective, randomised clinical trial was conducted in three secondary care hospitals in the Netherlands.ParticipantsPatients with primary knee/hip OA who were planned for TKA/THA were screened using the modified painDETECT Questionnaire. Patients whose painDETECT score indicated that sensitisation may be present were eligible for participation. 111 participants were included and randomly assigned 1:1 to an intervention or control group. The intervention group received additional duloxetine treatment, the control group did not receive any additional treatment but was allowed to continue with any pain medication they were already taking.InterventionsPreoperative oral treatment for 7 weeks with 60 mg/day of duloxetine was compared with usual care.Primary and secondary outcome measuresPrimary outcome measure was pain at 6 months after arthroplasty, assessed with the Pain Subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS) or the Hip disability and Osteoarthritis Outcome Score (HOOS) with a 0-100 scale. Secondary outcome measures were Visual Analogue Scale (VAS), and neuropathic-like pain measured using the modified PainDETECT Questionnaire. Longitudinal data collection included time points directly after duloxetine treatment, 1-day preoperatively, and 6 weeks, 6 months and 12 months postoperatively.ResultsMean improvement in the KOOS/HOOS pain subscale at 6 months postoperatively was 37 (SD 28.1) in the intervention group and 43 (SD 26.5) in the control group. No statistically significant difference was found in change score 6 months postoperatively between the two groups (p=0.280). 12 patients from the intervention group (21%) discontinued duloxetine due to adverse effects.ConclusionsPreoperative targeted treatment with duloxetine in end-stage knee and hip OA patients with sensitisation does not influence postoperative chronic residual pain after TKA/THA.Trial registration numberNTR4744.

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Preoperative serum circulating microRNAs as potential biomarkers for chronic postoperative pain after total knee replacement.

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Preoperative serum circulating microRNAs as potential biomarkers for chronic postoperative pain after total knee replacement.

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