The Combination of Preoperative Pain, Conditioned Pain Modulation, and Pain Catastrophizing Predicts Postoperative Pain 12 Months After Total Knee Arthroplasty.

OBJECTIVES: Approximately 20% of knee osteoarthritis patients undergoing total knee arthroplasty (TKA) report chronic postoperative pain. Studies suggest that preoperative variables such as impaired descending pain control, catastrophizing, function, and neuropathic pain-like symptoms may predict postoperative pain 12 months after TKA, but the combined prediction value of these factors has not been tested. The current prospective cohort study aimed to combine preoperative risk factors to investigate the predictive value for postoperative pain 12 months after TKA. DESIGN: Prospective cohort with follow-up 12 months after surgery. PATIENTS: A consecutive sample of 131 knee osteoarthritis patients undergoing TKA. METHODS: Pain intensity, Pain Catastrophizing Scale (PCS) scores, PainDETECT Questionnaire scores, conditioned pain modulation (CPM), and Oxford Knee Score (OKS) were obtained before and 12 months after TKA. RESULTS: TKA improved pain (P < 0.001), PCS scores (P < 0.001), PainDETECT Questionnaire scores (P < 0.001), and OKSs (P < 0.001). Preoperative pain correlated with preoperative PCS scores (r = 0.38, P  <  0.001), PainDETECT scores (r = 0.53, P  <  0.001), and OKSs (r = -0.25, P  =  0.001). Preoperative PainDETECT scores were associated with preoperative PCS scores (r = 0.53, P  <  0.001) and OKSs (r = -0.25, P  =  0.002). Higher postoperative pain was correlated with high preoperative pain (r = 0.424, P  <  0.001), PCS scores (r = 0.33, P  <  0.001), PainDETECT scores (r = 0.298, P  =  0.001), and lower CPM (r = -0.18, P  =  0.04). The combination of preoperative pain, PCS score, and CPM explained 20.5% of variance in follow-up pain. PCS scores had a significant effect on pain trajectory when accounting for patient variance (t  =  14.41, P  <  0.0005). CONCLUSION: The combination of high preoperative clinical pain intensity, high levels of pain catastrophizing thoughts, and impaired CPM may predict long-term postoperative pain 12 months after surgery.

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

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 < 0.05). Hsa-miR-146a-5p and preoperative pain intensity correlated positively with postoperative pain relief (respectively, R = 0.300, P = 0.006; R = 0.500, P < 0.001). DISCUSSION: This study showed that patients with a low postoperative pain relief present a dysregulation of circulating microRNAs. Altered circulatory microRNAs expression correlated with postoperative pain relief, indicating that microRNAs can serve as predictive biomarkers of pain outcome after surgery and hence may foster new strategies for preventing chronic postoperative pain after total knee replacement (TKR).

A Randomized, Controlled Trial of Total Knee Replacement.

BACKGROUND: More than 670,000 total knee replacements are performed annually in the United States; however, high-quality evidence to support the effectiveness of the procedure, as compared with nonsurgical interventions, is lacking. METHODS: In this randomized, controlled trial, we enrolled 100 patients with moderate-to-severe knee osteoarthritis who were eligible for unilateral total knee replacement. Patients were randomly assigned to undergo total knee replacement followed by 12 weeks of nonsurgical treatment (total-knee-replacement group) or to receive only the 12 weeks of nonsurgical treatment (nonsurgical-treatment group), which was delivered by physiotherapists and dietitians and consisted of exercise, education, dietary advice, use of insoles, and pain medication. The primary outcome was the change from baseline to 12 months in the mean score on four Knee Injury and Osteoarthritis Outcome Score subscales, covering pain, symptoms, activities of daily living, and quality of life (KOOS4); scores range from 0 (worst) to 100 (best). RESULTS: A total of 95 patients completed the 12-month follow-up assessment. In the nonsurgical-treatment group, 13 patients (26%) underwent total knee replacement before the 12-month follow-up; in the total-knee-replacement group, 1 patient (2%) received only nonsurgical treatment. In the intention-to-treat analysis, the total-knee-replacement group had greater improvement in the KOOS4 score than did the nonsurgical-treatment group (32.5 vs. 16.0; adjusted mean difference, 15.8 [95% confidence interval, 10.0 to 21.5]). The total-knee-replacement group had a higher number of serious adverse events than did the nonsurgical-treatment group (24 vs. 6, P=0.005). CONCLUSIONS: In patients with knee osteoarthritis who were eligible for unilateral total knee replacement, treatment with total knee replacement followed by nonsurgical treatment resulted in greater pain relief and functional improvement after 12 months than did nonsurgical treatment alone. However, total knee replacement was associated with a higher number of serious adverse events than was nonsurgical treatment, and most patients who were assigned to receive nonsurgical treatment alone did not undergo total knee replacement before the 12-month follow-up. (Funded by the Obel Family Foundation and others; MEDIC ClinicalTrials.gov number, NCT01410409.).

A Novel High Sensitivity Type II Collagen Blood-Based Biomarker, PRO-C2, for Assessment of Cartilage Formation.

N-terminal propeptide of type II collagen (PIINP) is a biomarker reflecting cartilage formation. PIINP exists in two main splice variants termed as type IIA and type IIB collagen NH2-propeptide (PIIANP, PIIBNP). PIIANP has been widely recognized as a cartilage formation biomarker. However, the utility of PIIBNP as a marker in preclinical and clinical settings has not been fully investigated yet. In this study, we aimed to characterize an antibody targeting human PIIBNP and to develop an immunoassay assessing type II collagen synthesis in human blood samples. A high sensitivity electrochemiluminescence immunoassay, hsPRO-C2, was developed using a well-characterized antibody against human PIIBNP. Human cartilage explants from replaced osteoarthritis knees were cultured for ten weeks in the presence of growth factors, insulin-like growth factor 1 (IGF-1) or recombinant human fibroblast growth factor 18 (rhFGF-18). The culture medium was changed every seven days, and levels of PIIBNP, PIIANP, and matrix metalloproteinase 9-mediated degradation of type II collagen (C2M) were analyzed herein. Serum samples from a cross-sectional knee osteoarthritis cohort, as well as pediatric and rheumatoid arthritis samples, were assayed for PIIBNP and PIIANP. Western blot showed that the antibody recognized PIIBNP either as a free fragment or attached to the main molecule. Immunohistochemistry demonstrated that PIIBNP was predominately located in the extracellular matrix of the superficial and deep zones and chondrocytes in both normal and osteoarthritic articular cartilage. In addition, the hsPRO-C2 immunoassay exhibits acceptable technical performances. In the human cartilage explants model, levels of PIIBNP, but not PIIANP and C2M, were increased (2 to 7-fold) time-dependently in response to IGF-1. Moreover, there was no significant correlation between PIIBNP and PIIANP levels when measured in knee osteoarthritis, rheumatoid arthritis, and pediatric serum samples. Serum PIIBNP was significantly higher in controls (KL0/1) compared to OA groups (KL2/3/4, p = 0.012). The hsPRO-C2 assay shows completely different biological and clinical patterns than PIIANP ELISA, suggesting that it may be a promising biomarker of cartilage formation.

Successful conservative treatment of patients with MRI-verified meniscal lesions.

PURPOSE: To follow a prospective cohort of consecutive patients with MRI-verified meniscal lesions to identify pre-treatment prognostic factors for long-term results following arthroscopic or conservative treatment. METHODS: In the course of 1 year, 291 patients with knee pain and clinically suspected of meniscal lesion were referred to the regional orthopaedic division and subjected to MRI and clinical examination by an experienced surgeon. Patients with MRI-verified meniscal lesions were treated according to an arthroscopy restrictive strategy meaning that treatment was initiated by conservative treatment. Arthroscopy was only performed if satisfying pain relief was not obtained. The Lysholm score and Knee Injury and Osteoarthritis Outcome Score (KOOS) were obtained at baseline and after 12-24 months. A multiple linear regression model was used to investigate which pre-treatment prognostic factors were associated with improvement in the KOOS subscale pain from baseline to follow-up. RESULTS: An MRI-verified meniscal lesion was found in 185 patients (64%). Among these, 58% were treated successfully by conservative treatment. A high KOOS subscale pain score at baseline was associated with less improvement from baseline to follow-up. Bucket-handle lesions were associated with larger improvement from baseline to follow-up compared to flap-tear lesions. CONCLUSION: MRI findings and clinical status measured by KOOS subscale pain are prognostic for improvement among patients treated for MRI-verified meniscal lesions. Good results were observed for both operative and conservative treatment. The success rate for conservative treatment was 58%. LEVEL OF EVIDENCE: Prospective cohort study, Level II.

Nonoperative treatment improves pain irrespective of radiographic severity. A cohort study of 1,414 patients with knee osteoarthritis.

BACKGROUND AND PURPOSE: The discrepancy between symptoms and radiographic severity of knee osteoarthritis (OA) is well described. However, little is known about whether radiographic severity is predictive of the clinical result of nonoperative treatment. We investigated whether radiographic severity and treatment type were associated with improvements in pain after nonoperative treatment of patients with knee OA. PATIENTS AND METHODS: A 5-year consecutive series of patients deemed not eligible for total knee arthroplasty (TKA) by an experienced orthopedic surgeon was contacted 1-5 years later. Radiographic severity, age, sex, and BMI were registered at the consultation. At follow-up, patients were asked to answer a questionnaire on type of treatment and improvements in pain after treatment. RESULTS: Of 1,848 patients who were not eligible for TKA, 1,414 (77%) completed the follow-up questionnaire (mean age 66 (24-96) years; 55% women). Radiographic severity was not associated with improvements in pain even after adjusting for treatment type, age, sex, and BMI (p > 0.1). The odds ratio of improvement was higher by a factor of 2 in patients who received physiotherapy or multimodal treatment than in patients who did not. INTERPRETATION: Radiographic severity was not associated with improvements in pain after nonoperative treatment. Patients who are not eligible for TKA can confidently be referred to nonoperative treatment even if they have severe radiographic OA. The treatment should preferably be multimodal, including physiotherapy, as recommended in Danish and international clinical guidelines.

Small distal muscles and balance predict survival in end-stage renal disease.

BACKGROUND/AIMS: Survival for patients on renal replacement therapy (RRT) has been shown to correlate to the level of physical activity and exercise capacity. We examined whether composite measures of functional status at the start of RRT predict survival. METHODS: In this retrospective study, the same physiotherapist, using a standardized battery of tests for functional status, tested 134 patients at the start of RRT. RESULTS: At the end of the observation period, 112 patients (84%) were still alive. Age (p < 0.0001), co-morbidity (p = 0.028), hand grip strength (right: p = 0.0065; left: p = 0.0039), standing heel rise (right: p = 0.011; left: p = 0.004) and functional reach (p = 0.015) were significant predictors of survival. After adjustment for sex, age and co-morbidity, hand grip strength left (p = 0.023) was a significant predictor of survival. CONCLUSION: Hand grip strength, standing heel rise and functional reach at the start of RRT seem to affect survival. A 50% reduction in hand grip strength left was associated with an almost 3-fold increase in mortality. Deterioration of function in small distal muscles and balance may be early signs of uraemic myopathy. A relatively simple and clinically feasible battery of tests can help detect patients at risk.

Type X collagen levels are elevated in serum from human osteoarthritis patients and associated with biomarkers of cartilage degradation and inflammation.

BACKGROUND: Osteoarthritis (OA) is the most common degenerative joint disease, of which the pathogenesis is inadequately understood. Hypertrophy-like changes have been observed as part of the progression of OA. The aim of the study was to develop and characterize a novel biomarker of chondrocytes hypertrophy and investigate how this marker was associated with cartilage degradation and inflammation in patients with various degrees of OA. METHODS: A competitive ELISA, C-Col10, applying a well-characterized monoclonal antibody was developed as a biomarker of chondrocyte hypertrophy through measurement of type X collagen (ColX). The levels of C-Col10, C2M (matrix metalloproteinase-derived fragments of type II collagen) and hsCRP (high sensitive C-reactive protein) were quantified by ELISAs in serum of 271 OA patients stratified by Kellgren-Lawrence (KL) score 0-4. Associations between serum levels of the three biomarkers (log transformed) were analyzed by Pearson's correlation and differences in C-Col10 levels between patients with high and low levels of inflammation measured by hsCRP were analyzed by ANOVA. RESULTS: We developed a C-Col10 assay measuring the C-terminus of ColX. We found significantly higher levels of ColX in patients with KL score 2 compared to patients with no radiographic evidence of OA (KL0) (p = 0.04). Levels of ColX were significantly elevated in OA patients with above normal hsCRP levels (p < 0.0001), as well as significantly correlated with levels of C2M (r = 0.55, p < 0.0001), which suggested that chondrocyte hypertrophy was associated with inflammation and cartilage degradation. There was no correlation between C2M and hsCRP. Age and BMI adjustment didn't change the results. Immuno-staining revealed that ColX was predominately located around the hypertrophic chondrocytes and the clustered chondrocytes indicating that C-Col10 measures may be linked to cartilage hypertrophic changes. CONCLUSIONS: We developed a novel assay, C-Col10, for measurement of chondrocyte hypertrophy and found its levels significantly elevated in OA patients with KL score of 2, and also in OA patients with above normal hsCRP levels. Concentration of C-Col10 strongly correlated with levels of C2M, a marker of cartilage destruction. The data suggest that chondrocyte hypertrophy and subsequent collagen X fragmentation seem to be increased in a subset of patients with inflammatory OA.

Danish surgeons allow the most athletic activities after total hip and knee replacement.

BACKGROUND AND PURPOSE: Counselling patients for or against athletic activities after well performed total hip arthroplasty (THA) and total knee arthroplasty (TKA). Level of evidence is low, and the current international guidelines are based on North American expert opinions in 2001 and 2008. Could technical and operative development and social or cultural differences apply for different counselling? METHODS: All Danish experts in head of departments performing more than 100 THAs or TKAs per year, were invited to fill in a questionnaire regarding the most popular sport activities in the Danish 60-69 years old population RESULTS: Response rate was 74 and 89% for the TKA and THA departments, respectively. A pronounced variation between the departments was observed and compared to the latest published US recommendations in 2007, the present Danish recommendations are significantly more liberal. Athletic activities are now allowed by 87% of the Danish arthroplasty departments. Of these 55% allow for high-impact activities after THA compared to 21% in US in 2007 (p < 0.0001). Recommendations for TKA patients are less liberal. Only 38% of the departments allow for high-impact activities after TKA compared to the 55% after THA (p < 0.0001). INTERPRETATION: Based on the pronounced variation between departments and the fact that a highly significant trend was observed over 5 years on an undocumented basis it was concluded that there is an imminent need for a higher scientific level on this issue­which hopefully can develop in a few years using PROMs in large scale follow-up studies.

The gait pattern is not impaired in subjects with external snapping hip: a comparative cross-sectional study.

BACKGROUND: Symptomatic external snapping hip is a painful condition, where pain in the trochantor region and limitations of daily activity dominate clinical findings. The aetiology of symptomatic external snapping hip is elusive, but previous studies have suggested that weakness of the hip abductors and an altered walking pattern may play a role in the development of symptomatic external snapping hip. The aim of this study was to compare the walking pattern and muscular activity of the hip muscles between subjects with symptomatic external snapping hip and healthy subjects. METHODS: Thirteen subjects with diagnosed symptomatic external snapping hip (age: 25.5 years) were matched with 13 healthy subjects (age: 25.6 years). Joint kinematics and kinetics of the lower extremity were quantified by the peak hip adduction angle; the average knee rotation range of motion (ROM) and the peak valgus knee angle after data recording using a Vicon 612 motion capture system. Muscle activity was recorded bilaterally using surface electromyography (sEMG) on five muscles: gluteus maximus, gluteus medius, tensor fascia latae, rectus femoris and biceps femoris. A paired t-test was used to evaluate differences between the two groups. RESULTS: No significant differences were found between the groups concerning the peak hip adduction angle, the average knee rotation ROM, and the static valgus knee angle. No significant between-group differences were found concerning all other kinematics, kinetics or muscle activity. In subjects with symptomatic external snapping hip activity of the gluteus medius muscle during the acceptance phase of walking was 0.58 ± 0.19 whereas the activity was 0.68±0.07 in the asymptomatic group (p=0.115). CONCLUSIONS: No significant differences in the walking pattern were found between subjects with symptomatic external snapping hip and healthy subjects. This suggest that subjects with symptomatic external snapping hip does not have an impaired gait pattern.

Pre-operative patient education is associated with decreased risk of arthrofibrosis after total knee arthroplasty: a case control study.

The purpose was to investigate risk factors for postoperative stiffness and long-term outcome following manipulation under anaesthesia (MUA). In one of the five Danish regions, all patients in a 4-year period who received MUA following total knee arthroplasty (N=36) were included in two case-control studies. Data on potential risk factors were extracted from the Danish Knee arthroplasty Register and from a postal questionnaire including long-term outcome measures regarding pain, function and quality of life (Oxford Knee Score and EQ-5D). Previous knee surgery and a high preoperative Knee Society Function Score were significant risk factors, whereas attending a preoperative information meeting was associated with a significantly decreased risk of postoperative stiffness requiring MUA (P<0.001). The long-term results following MUA (1-5 years) were equivalent to patients without postoperative stiffness.

Total knee replacement plus physical and medical therapy or treatment with physical and medical therapy alone: a randomised controlled trial in patients with knee osteoarthritis (the MEDIC-study).

BACKGROUND: There is a lack of high quality evidence concerning the efficacy of total knee arthroplasty (TKA). According to international evidence-based guidelines, treatment of knee osteoarthritis (KOA) should include patient education, exercise and weight loss. Insoles and pharmacological treatment can be included as supplementary treatments. If the combination of these non-surgical treatment modalities is ineffective, TKA may be indicated. The purpose of this randomised controlled trial is to examine whether TKA provides further improvement in pain, function and quality of life in addition to optimised non-surgical treatment in patients with KOA defined as definite radiographic OA and up to moderate pain. METHODS/DESIGN: The study will be conducted in The North Denmark Region. 100 participants with radiographic KOA (K-L grade ≥2) and mean pain during the previous week of ≤ 60 mm (0-100, best to worst scale) who are considered eligible for TKA by an orthopaedic surgeon will be included. The treatment will consist of 12 weeks of optimised non-surgical treatment consisting of patient education, exercise, diet, insoles, analgesics and/or NSAIDs. Patients will be randomised to either receiving or not receiving a TKA in addition to the optimised non-surgical treatment. The primary outcome will be the change from baseline to 12 months on the Knee Injury and Osteoarthritis Outcome Score (KOOS)(4) defined as the average score for the subscale scores for pain, symptoms, activities of daily living, and quality of life. Secondary outcomes include the five individual KOOS subscale scores, EQ-5D, pain on a 100 mm Visual Analogue Scale, self-efficacy, pain pressure thresholds, and isometric knee flexion and knee extension strength. DISCUSSION: This is the first randomised controlled trial to investigate the efficacy of TKA as an adjunct treatment to optimised non-surgical treatment in patients with KOA. The results will significantly contribute to evidence-based recommendations for the treatment of patients with KOA. TRIAL REGISTRATION: Clinicaltrials.gov reference: NCT01410409.

A novel method for measuring in-shoe navicular drop during gait.

Analysis of foot movement is essential in the treatment and prevention of foot-related disorders. Measuring the in-shoe foot movement during everyday activities, such as sports, has the potential to become an important diagnostic tool in clinical practice. The current paper describes the development of a thin, flexible and robust capacitive strain sensor for the in-shoe measurement of the navicular drop. The navicular drop is a well-recognized measure of foot movement. The position of the strain sensor on the foot was analyzed to determine the optimal points of attachment. The sensor was evaluated against a state-of-the-art video-based system that tracks reflective markers on the bare foot. Preliminary experimental results show that the developed strain sensor is able to measure navicular drop on the bare foot with an accuracy on par with the video-based system and with a high reproducibility. Temporal comparison of video-based, barefoot and in-shoe measurements indicate that the developed sensor measures the navicular drop accurately in shoes and can be used without any discomfort for the user.

The Role of Nuclear Medicine Imaging with 18F-FDG PET/CT, Combined 111In-WBC/99mTc-Nanocoll, and 99mTc-HDP SPECT/CT in the Evaluation of Patients with Chronic Problems after TKA or THA in a Prospective Study.

BACKGROUND: The aim of this prospective study was to assess the diagnostic value of nuclear imaging with 18F-FDG PET/CT (FDG PET/CT), combined 111In-WBC/99mTc-Nanocoll, and 99mTc-HDP SPECT/CT (dual-isotope WBC/bone marrow scan) for patients with chronic problems related to knee or hip prostheses (TKA or THA) scheduled by a structured multidisciplinary algorithm. MATERIALS AND METHODS: Fifty-five patients underwent imaging with 99mTc-HDP SPECT/CT (bone scan), dual-isotope WBC/bone marrow scan, and FDG PET/CT. The final diagnosis of prosthetic joint infection (PJI) and/or loosening was based on the intraoperative findings and microbiological culture results and the clinical follow-up. RESULTS: The diagnostic performance of dual-isotope WBC/bone marrow SPECT/CT for PJI showed a sensitivity of 100% (CI 0.74-1.00), a specificity of 97% (CI 0.82-1.00), and an accuracy of 98% (CI 0.88-1.00); for PET/CT, the sensitivity, specificity, and accuracy were 100% (CI 0.74-1.00), 71% (CI 0.56-0.90), and 79% (CI 0.68-0.93), respectively. CONCLUSIONS: In a standardized prospectively scheduled patient group, the results showed highly specific performance of combined dual-isotope WBC/bone marrow SPECT/CT in confirming chronic PJI. FDG PET/CT has an appropriate accuracy, but the utility of its use in the clinical diagnostic algorithm of suspected PJI needs further evidence.

Pain, sensitization and physical performances in patients with chronic painful knee osteoarthritis or chronic pain following total knee arthroplasty: An explorative study.

BACKGROUND: The aim of this study was to assess clinical pain, pain sensitization and physical performances to profile patients with chronic painful knee osteoarthritis (OA) or pain after total knee arthroplasty (TKA). Examining the interactions between pain mechanisms and physical performances would enable us to investigate the underlying explanatory relationships between these parameters. METHODS: In this explorative study, 70 patients with chronic painful knee OA (N = 46) or chronic pain after TKA (N = 24) were assessed for clinical pain, quantitative sensory profiling (mechanical pinprick pain sensitivity, temporal summation (TS) and conditioned pain modulation), physical performances (chair stand, walk and stair climb tests) and self-reported outcomes. Between-group comparisons were made using ANCOVA tests and associations between outcomes were analysed using multivariate linear regression models. RESULTS: Overall, no differences between groups regarding clinical pain and quantitative sensory profiling outcomes were observed. Physical performances were lower in the TKA group compared with the OA group with moderate-to-large effect sizes, and a tendency towards better scores in self-reported outcomes for the OA group was observed with small-to-moderate effect sizes. Self-reported function seems to be associated with physical performances in the TKA group. Sensitization (TS) appears to be associated with poorer physical performances in the OA group. CONCLUSIONS: Similar profiles for pain intensity, signs of sensitization and conditioned pain modulation were observed. Patients with TKA seems to have impaired physical performances compared with the OA group, underlining the importance of targeting physical performances. Only the OA patients showed an association between sensitization (TS) and physical performance. SIGNIFICANCE: Quantitative pain profiling assessment was used to assess pain intensities and pain mechanisms. We observed associations between physical performances and temporal summation in the OA group underlining the importance of assessing motor functions and pain mechanisms in the same trial. We observed lower levels of physical performances in the TKA group compared with the OA group, suggesting that examination and rehabilitation of physical performances is essential for TKA patients with chronic pain.

The association between sleep quality, preoperative risk factors for chronic postoperative pain and postoperative pain intensity 12 months after knee and hip arthroplasty.

BACKGROUND: Chronic postoperative pain following total joint replacement (TJA) is a substantial clinical problem, and poor sleep may affect predictive factors for postoperative pain, such as pain catastrophizing. However, the magnitude of these associations is currently unknown. This exploratory study investigated (1) the relationship between preoperative sleep quality, clinical pain intensity, pain catastrophizing, anxiety, and depression and (2) their associations with chronic postoperative pain following TJA. METHODS: This secondary analysis from a larger randomized controlled trial included rest pain intensity (preoperative and 12 months postoperative; visual analogue scale, VAS), preoperative Pittsburgh Sleep Quality Index (PSQI), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS) data from 74 knee and 89 hip osteoarthritis (OA) patients scheduled for TJA. Poor sleepers were identified based on preoperative PSQI scores higher than 5. RESULTS: Poor sleepers demonstrated higher preoperative VAS, pain catastrophizing, anxiety, and depression compared with good sleepers (all p < 0.003). Preoperative PSQI (ß = 0.23, p = 0.006), PCS (ß = 0.44, p < 0.005), and anxiety (ß = 0.18, p = 0.036) were independent factors for preoperative VAS. Preoperative VAS (ß = 0.32, p < 0.005), but not preoperative sleep quality (ß = -0.06, p = 0.5), was an independent factor for postoperative VAS. CONCLUSION: The OA patients reporting poor preoperative sleep quality show higher preoperative pain, pain catastrophizing, anxiety, and depression. High preoperative pain intensity, but not poor sleep quality, was associated with higher chronic postoperative pain intensity. Future studies are encouraged to explore associations between sleep and chronic postoperative pain.

Circulating long non-coding RNA signature in knee osteoarthritis patients with postoperative pain one-year after total knee replacement.

OBJECTIVES: The incidence of chronic postoperative pain after total knee replacement (TKR) is approx. 20%, and hence preoperative risk factors are important to identify. Recent studies have indicated that preoperative inflammatory markers might hold prognostic information for the development of chronic postoperative pain. Long non-coding RNA (lncRNA) regulates the expression of genes related to e.g. inflammatory processes. The current study aimed to investigate the preoperative lncRNA signature as possible preoperative predictive markers for chronic postoperative pain following TKR. METHODS: Serum samples, collected preoperatively from 20 knee osteoarthritis (KOA) patients, were analyzed for 84 validated circulatory lncRNA. Pain intensity was assessed using a visual analog scale (VAS) before and one-year after TKR. Differences for the lncRNA expression were analyzed between patients with chronic postoperative pain (VAS≥3) and those with a normal postoperative recovery (VAS<3). RESULTS: LncRNA Myeloid Zinc Finger 1 Antisense RNA 1 (MZF1-AS1) (fold change -3.99; p-value: 0.038) (shown to be involved neuropathic pain) Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) (fold change -3.39; p-value: 0.044) (shown to be involved neuropathic pain); Patched 1 pseudogene (LOC100287846) (fold change -6.99; p-value: 0.029) (unknown in pain) were down-regulated preoperatively in the group with chronic postoperative pain compared to the group normal postoperative pain recovery. CONCLUSIONS: These findings suggest, that TKR patients with chronic postoperative pain present preoperative downregulations of three specific lncRNA detectable at the systemic level. The presented study might give new insights into the complexity of chronic postoperative pain development and show how non-coding RNA plays a role in the underlying molecular mechanisms of pain.

Patients With High Chronic Postoperative Knee Pain 5 Years After Total Knee Replacement Demonstrate Low-grad Inflammation, Impairment of Function, and High Levels of Pain Catastrophizing.

OBJECTIVES: Total knee replacement (TKR) normally provides improvements of physical function and reduces pain. However, ∼20% of the patients report chronic postoperative knee pain. The aims of the present study were to assess the pain, physical function, and physiological characteristics 5 years after TKR surgery. MATERIALS AND METHODS: Eighty patients were recruited 5 years after TKR and divided into 2 groups based on their average 24-hour knee pain intensity assessed on a visual analog scale (VAS 0 to 10) ("high pain group": VAS≥3; "low pain group": VAS<3). The patients completed the PainDETECT Questionnaire (PDQ), Oxford Knee Score (OKS), Pain Catastrophizing Scale, and Forgotten Joint Score-12. Furthermore, the patients underwent a clinical examination of the knees and high-sensitivity serum C-reactive protein was measured as an inflammatory marker. RESULTS: A total of 53% of the patients in the high pain group were not satisfied with the outcome, while only 11% of the patients in the low pain group was not satisfied, and the pain intensities in the 2 groups were 5.1 (4.6 to 5 to 6) and 1.1 (0.6 to 1.5) (P<0.001), respectively. Furthermore, the high pain group demonstrates worse scores in: Forgotten Joint Score-12 (P=0.001), OKS function (P<0.001), OKS pain (P<0.001), and Pain Catastrophizing Scale (P<0.001).The high pain group demonstrated increased level of high-sensitivity serum C-reactive protein (4.3 mg/L [3.2 to 5.5] vs. 1.7 mg/L [1.2 to 2.2], P<0.001), and decreased range of motion in the knee (110 vs. 119-degree range of motion, P=0.013). DISCUSSION: Patients with high chronic postoperative knee pain 5 years after TKR demonstrate decreased physical function, higher levels of catastrophizing thoughts, and increased levels of inflammation.

Intra-articular hyaluronan is without clinical effect in knee osteoarthritis: a multicentre, randomised, placebo-controlled, double-blind study of 337 patients followed for 1 year.

OBJECTIVE: To examine the long-term efficacy and safety of five intra-articular injections with hyaluronan in knee osteoarthritis. METHODS: A multicentre, randomised, placebo-controlled double-blind study of 337 patients fulfilling the American College of Rheumatology (ACR) criteria for knee osteoarthritis (clinical and laboratory) and with a Lequesne algofunctional index score (LFI) of 10 or greater. Patients received a hyaluronan product (sodium hyaluronate; Hyalgan) (n=167) or saline (n=170) intra-articularly weekly for 5 weeks and were followed up to 1 year. Time to recurrence was the primary efficacy parameter. LFI, pain on walking 50 m based on visual analogue scale (VAS pain 50 m), paracetamol consumption, patients' global assessment, Nottingham health profile, joint effusion and number of responders were secondary efficacy parameters. The efficacy parameters were analysed by intention to treat (ITT) and per protocol (PP). All adverse events (AE) were recorded as safety parameters. RESULTS: Time to recurrence showed no significant treatment effect (ITT analysis, p=0.26). Change from baseline in LFI and VAS pain 50 m for the ITT population showed no treatment effect. Paracetamol consumption, patients' global assessment, responder rates and AE displayed no significant difference between treatment groups, analysed by both ITT and PP. Treatment compliance was 95% in the hyaluronan group and 99% in the placebo group. No safety problems were registered. CONCLUSION: In patients fulfilling the ACR criteria for osteoarthritis of the knee with moderate to severe disease activity (LFI > or = 10), five intra-articular injections of hyaluronan did not improve pain, function, paracetamol consumption or other efficacy parameters 3, 6, 9 and 12 months after the treatment.

Serum Inflammatory Markers in Patients With Knee Osteoarthritis: A Proteomic Approach.

OBJECTIVES: Osteoarthritis (OA) is known to be a slowly progressive disease that alters all tissue compartments of the joint involved with a characteristic degradation of the cartilage, bone remodeling, and inflammation. One of the prominent symptoms in OA patients is pain, but a few radiologic, inflammatory, or structurally related biomarkers have shown few if any associations with pain. This study aimed to assess serum levels of 92 markers involved in inflammatory pathways in patients with knee osteoarthritis (KOA) and evaluate their possible associations with the clinical pain intensity. MATERIALS AND METHODS: Serum samples were collected from 127 KOA patients and 39 healthy participants with no knee pain. Each serum sample was analyzed for 92 inflammatory markers using the Proximity Extension Array (PEA) technology. Clinical pain intensity was assessed using a Visual Analog Scale, and patients completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. RESULTS: Fifteen markers were significantly different when comparing KOA patients and healthy participants. Two markers, fibroblast growth factor-21 and Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), correlated positively with pain intensity (R=0.235, P=0.008; R=0.233, P=0.008). Moreover, a linear regression model showed interleukin-6, macrophage colony-stimulating factor 1, fibroblast growth factor-21, and tumor necrosis factor superfamily member 12 (TWEAK) as significant independent parameters for pain intensity. DISCUSSION: The associations between specific cytokines and KOA pain intensities provide new insights into the understanding of the underlying factors driving the pain in OA.