Pain In Osteoarthritis Patients Research Articles

The Effectiveness of Herbal Poultice in Relieving Pain and Flexibility in Osteoarthritis Patients

Knee osteoarthritis (OA) is a chronic condition that causes joint degradation and primarily affects the elderly, reducing their quality of life and physical movements. The objective of this study was to determine the efficacy of Thai herbal poultice in relieving pain in OA patients. A single-blind, randomized controlled trial was conducted amongst OA patients at Integrative medicine clinic, Chulabhorn International College of Medicine, Thammasat University, Thailand. Participants were randomly allocated to the Thai herbal poultice or the diclofenac gel group (N=30). The main outcomes were evaluated using visual analog scale (VAS), isokinetic testing, goniometer, and knee injury and osteoarthritis outcome scores (KOOS) at different time assessment. Data were analyzed by the paired t-test and analysis of variance (ANOVA). Thai herbal poultice and diclofenac group showed a significant difference in both the VAS pain scores, extension and flexion as well as KOOS scores (P < 0.01 in both groups). In addition, when compared to diclofenac group, Thai herbal poultice group were significantly improve pain score at the sixth time point following the intervention (P < 0.01). Furthermore, no patients have experienced allergic reactions to therapies. In conclusion, Thai herbal poultice showed more efficiency in reducing pain scores than diclofenac gel without causing undesirable side effects.

Evaluation of efficacy of topical herbal analgesic Arthrella Ointment in Osteoarthritic Patients

Osteoarthritis (OA) is a chronic condition involving degradation of cartilage within the joints mostly found in Elderly population causing immense pain and disability in Patients, NSAIDs are the first line of drug in conventional medicine to manage pain. But it leads to Gastrointestinal, Cardiovascular, Renal and other systemic AEs. Arthrella Ointment being a Topical-Herbal ointment has no reported side effects and AEs. Thus, a safe treatment option to alleviate pain in OA Patients. In this Clinical study 87 Subjects with OA were divided in two groups, one was treated with Arthrella Ointment for 4 weeks and results were compared with Placebo Control Group. The result showed better WOMAC and VAS scores after 4 weeks along with statistically significant difference in the relief of pain in the two groups. This effect increased regularly over the whole study period. There were no adverse reactions attributed to the Arthrella ointment. Thus, it was concluded that Arthrella Ointment is effective in pain management Associated with OA without any AEs and Side Effects.

The Effect of Massage on Pain Reduction in Osteoarthritis Knee: Literature Review

One way to reduce OA complaints is by using massage methods. Massage is a condition of physical recovery from certain disorders or diseases through muscle and physical straightening techniques so that this method has good credibility. Massage is the art of hand movement that aims to get pleasure and maintain health. This mechanical hand movement will create a sense of calm and comfort for the recipient. This study aims to determine the effect of massage on pain relief in knee osteoarthritis. This study uses a critical review approach, carried out using a PICO search in several databases such as Google Scholar, PubMed, and Scimago. From that search, 5 journals were obtained which showed that the frequency was 2 times a week, with a duration of 20 minutes, carried out 2 times a week for 8 weeks. With p<0.001 showed significant results in relieving pain in osteoarthritis patients.

Sex-specific differences in telomere length of patients with primary knee osteoarthritis.

Accelerated telomere shortening is associated with age-related diseases, including osteoarthritis (OA). We aimed to determine the relative telomere length (TL) in leukocytes and cartilage of patients with primary knee OA and to investigate factors that may affect TL in OA. Relative TL measurements were performed using qPCR in leukocytes of 612 individuals (310 patients with primary knee OA undergoing total knee arthroplasty (TKA) and 302 unaffected controls). We also analysed cartilage in 57 of the 310 OA patients, measuring relative TL in severely affected and less affected (control) cartilage collected from the same knee. Cartilage TLs were compared to leukocyte TLs in all 57 patients. A significant sex-by-disease-status interaction was found in regard to relative TL. Controlling for age, the average difference of leukocyte TL between female OA patients versus female controls was 0.217 units greater than that between male OA patients versus male controls (95% CI; [0.014, 0.421]). Relative TL comparison of severely and less affected cartilage samples from the same joint showed attrition of telomeres corresponding to disease severity (0.345 mean TL difference with 95% CI of [0.151, 0.539]) in the joint. We also noted that both severely and less affected cartilage had shorter telomeres than leukocytes collected from the same patient. Severe and moderate pain in OA patients was associated with shorter TL in leukocytes, but there was no association with depression or smoking in leukocytes and cartilage. Our study indicates that sex is an important factor in OA contributing to leukocyte and cartilage TL and that pain in OA shows an inverse association only with leukocyte TL.

Responsiveness and interpretability of the pain subscale of the Knee and Hip Osteoarthritis Outcome Scale (KOOS and HOOS) in osteoarthritis patients according to COSMIN guidelines.

The pain subscales of the Knee and Hip Osteoarthritis Outcome Scores (KOOS and HOOS) are among the most frequently applied, patient reported outcomes to assess pain in osteoarthritis patients and evaluation of the results after Total Knee Arthroplasty (TKA) and Total Hip Arthroplasty (THA). For the evaluation of change over time it is essential to know the responsiveness and interpretability of these measurement instruments. Aim of this study is to investigate responsiveness and interpretability of the KOOS and HOOS pain subscales in patients with knee or hip OA and patients after TKA and THA as recommended by COSMIN guidelines. COSMIN stands for COnsensus based Standards for the selection of health Measurement Instruments. COSMIN recommends methods for assessing responsiveness similar to those assessing validity, using extensive hypothesis testing to assess criterion validity and construct validity of the change score. This clinimetric study was conducted using data obtained from the Duloxetine in OsteoArthritis (DOA) trial. Primary knee or hip osteoarthritis patients were included. During the study, half of the participants received pre-operative targeted treatment with duloxetine, and all participants received TKA or THA. Patients filled out a set of patient-reported outcomes at several time points. Using the criterion validity approach the change scores of the KOOS and HOOS pain subscales directly after duloxetine treatment but before TKA and THA were correlated to the Patient Global Improvement anchor-question (PGI-I). Receiver Operating Characteristic curves (ROC curves) were obtained. Using the construct validity approach, hypothesis testing was conducted investigating the correlation between change scores in the KOOS and HOOS pain subscale with change scores in other questionnaires six months after TKA and THA. For interpretability, an anchor-based approach was used to consider the Minimally Important Change (MIC) of the KOOS and HOOS pain subscale. We compared the outcomes after duloxetine treatment and six months after TKA and THA in order to investigate any response shift. Ninety-three participants (53 knee patients and 41 hip patients) were included. Mean change was 4.3 and 4.6 points after conservative treatment for knee and hip OA patients respectively and 31.7 and 48.8 points after TKA and THA respectively. The KOOS and HOOS pain subscales both showed a gradual increase in change scores over the different categories of improvement on the PGI-I, with an Area Under the Curve of 0.72 (95% CI 0.527-0.921) and 0.79 (95% CI 0.588-0.983) respectively. Of the predefined hypotheses, 69% were confirmed for both subscales. The MICs were between 12.2 to 37.9 for the KOOS pain subscale, and between 11.8 to 48.6 for the HOOS pain subscale, depending on whether the PGI-I was administered after conservative treatment, or six months after TKA and THA. This study endorses the responsiveness of the KOOS and HOOS pain subscales in patients with knee or hip OA and patients after TKA and THA based on construct and criterion validity approaches. The KOOS pain subscale might be able to detect the MIC at an individual level after arthroplasty, but both the KOOS and HOOS pain subscales were not able to do so after conservative treatment. This study is the first to report a considerable response shift in MIC of the KOOS and HOOS pain subscales. This should be taken into consideration when evaluating MIC of the KOOS and HOOS pain subscale after conservative versus operative treatment. Future research should present more reference data regarding MIC scores after different treatments.

Effect of Theraband Exercise on Knee Pain Reduction in Osteoarthritis Patients

Background: Osteoarthritis (OA) is a degenerative joint disease associated with damage to joint cartilage, where a complex joint degradation process occurs, consisting of a repair process in the cartilage, bone, and synovium, followed by a secondary component of the inflammatory process. The primary cause of osteoarthritis is still not known for certain, but there are several risk factors that play a role, namely: age, gender, genetics, obesity, metabolic diseases, and other factors. This study aimed to examine the effect of theraband exercise on reducing knee pain in OA patients. Subjects and Method: This was a quasy experiment study conducted at Dr. Soedjono Hospital, in Magelang, Central Java, from May to June 2023. A sample of 33 knee osteoarthritis patients was selected using purposive sampling. Intervention group (n= 17) received Theraband exercise and control group (n= 16) received usual care. The dependent variable was knee pain. The independent variable was Theraband exercise. Knee pain was measured using a visual analogue scale (VAS). The data were tested using independent t test. Results: After intervention, mean of VAS score in the intervention group (Mean= 5.25; SD= 1.57) was slightly higher than control group (Mean= 5.13; SD= 1.75), but it was statistically non-significant (p= 0.848). Conclusion: Mean of VAS score in the intervention group is slightly higher than control group, but it is statistically non-significant. Keywords: theraband exercise, pain, osteoarthritis knee. Correspondence: Dela Ramona. Study Program of Physiotherapy, Faculty of Health Sciences, Universitas Muhammadiyah Surakarta. Jl. A. Yani Kartasura, Sukoharjo, Central Java, 57162 Email: delaramona26@gmail.com. Mobile: +6281347988116.

Randomized, double-blind, placebo-controlled study to evaluate the effect of treatment with an SPMs-enriched oil on chronic pain and inflammation, functionality, and quality of life in patients with symptomatic knee osteoarthritis: GAUDI study

BackgroundSpecialized pro-resolving mediators (SPMs), including 18-HEPE, 17-HDHA, and 14-HDHA are recognized as potentially therapeutic in inflammatory diseases because SPMs regulate the inflammation process, which leads to, for example; swelling and the sensation of pain. In osteoarthritis (OA), chronic pain is described as the symptom that reduces patients´ quality of life (QoL). The GAUDI study evaluated the efficacy of SPMs supplementation in reducing pain in the symptomatic knee of OA patients.MethodsThis randomized, multicenter, double-blind, and placebo-controlled parallel-group pilot study was performed in Spain and conducted on adults 18–68 years old diagnosed with symptomatic knee OA. Patients were enrolled in the study for up to 24 weeks, which included a 12-week intervention period and a follow-up visit on week 24. The primary endpoint was pain change measured through a Visual Analog Scale (VAS). Secondary endpoints included: Pain change evaluation, stiffness, and function according to the WOMAC index; assessment of constant, intermittent, and total pain according to the OMERACT-OARSI score; evaluation of changes in health-related QoL parameters; the use or not of concomitant, rescue, and anti-inflammatory medication; and safety and tolerability assessments.ResultsPatients were enrolled in the study from May 2018 to September 2021. VAS pain score was evaluated in the per protocol population (n = 51 patients), in which we observed a statistically significant reduction after 8 weeks (p = 0.039) and 12 weeks (p = 0.031) of treatment in patients consuming SPMs (n = 23 subjects) vs. placebo (n = 28 subjects). In line with the OMERACT-OARSI score, intermittent pain was reduced after 12 weeks with statistical significance (p = 0.019) in patients treated with SPMs (n = 23 subjects) vs. placebo (n = 28 subjects). Functional status as WOMAC score did not significantly change after SPMs or placebo consumption. Notably, patients consuming SPMs showed improvements in all five aspects of the EUROQoL-5, including a significant improvement in the usual-activities dimension. None of the patients required rescue medication, nor were any adverse events reported.ConclusionsThese findings suggest that sustained SPMs consumption reduces pain in OA patients while also improving their Quality of Life. These results also support the safety profile of SPMs supplementation.Trial registration NCT05633849. Registered 1 December 1 2022. Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT05633849

Pengaruh Pemberian Quadriceps isometric exercise terhadap perubahan nyeri osteoarthritis knee pada pasien Rumah Sakit Wijaya Kusuma Lumajang

Knee osteoarthritis is a disorder of the knee joint that is progressive, for example in the joint cartilage, synovial fluid and subchondral bone, and causes furs, ulcerations, and becomes thin. The main complaints that are often felt by sufferers of Knee Osteoarthritis are pain, limited range of joint motion, mechanical abnormalities, and limitations in carrying out daily functional activities. Complaints felt by sufferers of Knee Osteoarthritis can cause a decrease in the quality of life in the elderly. This study aims to identify the effect of quadriceps isometric exercise on changes in pain in osteoarthritis patients. This research has 21 respondents. The research design uses a pre-experimental type with a one group pretest and posttest approach. Bivariate analysis in this study used Wilcoxon. The results of this study were that the mean pain scale before quadriceps isometric exercise was 5.761, the mean pain scale after quadriceps isometric exercise in knee osteoarthritis patients was 2.857, and there was an effect of isometric quadriceps exercise on reducing pain in osteoarthritis patients at Wijaya Kusuma Hospital Lumajang with a p-value = 0.000 (p<0.05). It is hoped that this research can provide additional information based on data and theory to improve the quality of physiotherapy services by establishing a standard procedure for performing the quadriceps isometric exercise, especially in osteoarthritis patients.

Association between Sodium Intake and Biopsychosocial Factors with Knee Joint Pain in Osteoarthritis patient

Osteoarthritis is a chronic, degenerative disease with unknown etiology. Sodium can induce the secretion of IL-17 which causes cartilage destruction, decreases the secretion of chondrocytes and proteoglycans and induces the secretion of inflammatory mediators. No one knows that sodium is a risk factor for osteoarthritis. The aim of this study was to determine the effect of sodium intake and biopsychosocial factors on knee joint pain in Osteoarthritis patients. This study was an observational study conducted at the Orthopedic Outpatient Poly with a quantitative descriptive method with cross sectional sampling. Data were taken through interviews using the Semi Quantitative Food Frequency Questionnaire and Visual Analog Score. The data obtained were analyzed using Partial Least Square (p≤0.05). This research has obtained permission No. B/404/V/2021 and ethical approval No. 44/LE/2021. There were 52 subject in the inclusion criteria. The analysis of biopsychosocial factors (age, gender, body mass index, education, occupation) that affect knee joint pain was body mass index (p < 0.044). Sodium levels also affect gender (p< 0.046). The results of the correlation test between sodium levels and knee joint pain were 0.024. The higher the level of sodium intake caused an increase in knee joint pain in osteoarthritis patients. The study shows that there is a correlation between sodium intake, knee joint pain, gender and body mass index. It is necessary to reduce sodium intake in the diet of osteoarthritis patients

Eeffectiveness of olive oil application on knee pain among patients with osteoarthritis in selected hospitals

The aim of the present study was to assess the effect of olive oil application on knee pain among patients with osteoarthritis in selected hospitals at SangliMiraj and Kupwad corporation area. The study objectives were to assess the existing level of knee pain among patients with osteoarthritis in experimental and control group, to assess the level of knee pain after olive oil application in experimental group, to compare the level of pain in experimental and control group, and to find out the association of level of pain before olive oil application among patients with osteoarthritis with their selected demographic variables in both the groups. Hypothesis for this study was H0- There is no significant effect of olive oil application on level of knee pain among patients from experimental and control group. H1- There is significant effect of olive oil application on level of knee pain among patients from experimental and control group. Quantitative research approach with two groups pre test post test was used for this study. The conceptual framework used in this study was general system theory by Ludwig Von Bertalanffy. 60 samples were selected for the study by non-probability purposive sampling technique (30 samples of experimental group and 30 of control group). In experimental group, pain level was assessed prior to the intervention, after which olive oil is applied to the patients for once a day for 14 days and pain score level of day 1st,day 7th and day 14th was compared, Where as in control group daily routine care was given and pain score level was noted on same days as in experimental group. Data was collected using demographic data and Numerical pain rating scale. The data was analysed using descriptive and inferential statistics. The study result was, Variations are found in mean and SD scores in experimental and control group. P value is less than 0.005. There is significant difference in the level of knee pain among osteoarthritis patients. The reduction of pain is also seen in the control group, but not as significantly as in experimental group.Results shows that there is an effect of olive oil on knee pain among patients with osteoarthritis as the mean score for pain has seen to be reduced more in the experimental group as compared to that of control group.as a result, it can be concluded that using olive oil to alleviate knee pain in osteoarthritis patients is an effective and safe approach of pain control.

Application of Red Ginger Decorative Compress to Reduce Joint Pain in Osteoarthritis Patients in the Work Area Perumnas Public Health Center Lubuklinggau

Osteoarthritis is one of the most common types of arthritis, this condition causes joints to feel sore and stiff. Swelling can also occur in these joints. To determine the application of red ginger boiled compresses to reduce joint pain in Osteoarthritis sufferers in the Work Area of ​​the Public Health Center of Lubuklinggau City in 2021. Case study subjects used in family nursing case studies namely 2 families who experience osteoarthritis with knee pain problems on a scale of 4-5, female, 45-70 years old, have members who are more than 15 years old, can communicate well, do not suffer from complications of other diseases and do not take medication. Before the action is taken. Research results: during the application of red ginger decoction compresses are able to provide a comfortable effect and help in overcoming joint inflammation that occurs. The application of red ginger boiled compresses can reduce joint pain in osteoarthritis sufferers.

Study protocol for a randomised controlled trial of diacerein versus placebo to treat knee osteoarthritis with effusion-synovitis (DICKENS)

BackgroundThere is an unmet need for treatments for knee osteoarthritis (OA). Effusion-synovitis is a common inflammatory phenotype of knee OA and predicts knee pain and structural degradation. Anti-inflammatory therapies, such as diacerein, may be effective for this phenotype. While diacerein is recommended for alleviating pain in OA patients, evidence for its effectiveness is inconsistent, possibly because studies have not targeted patients with an inflammatory phenotype. Therefore, we will conduct a multi-centre, randomised, placebo-controlled double-blind trial to determine the effect of diacerein on changes in knee pain and effusion-synovitis over 24 weeks in patients with knee OA and magnetic resonance imaging (MRI)-defined effusion-synovitis.MethodsWe will recruit 260 patients with clinical knee OA, significant knee pain, and MRI-detected effusion-synovitis in Hobart, Melbourne, Adelaide, and Perth, Australia. They will be randomly allocated to receive either diacerein (50mg twice daily) or identical placebo for 24 weeks. MRI of the study knee will be performed at screening and after 24 weeks of intervention. The primary outcome is improvement in knee pain at 24 weeks as assessed by a 100-mm visual analogue scale (VAS). Secondary outcomes include improvement in volumetric (ml) and semi-quantitative (Whole-Organ Magnetic Resonance Imaging Score, 0–3) measurements of effusion-synovitis using MRI over 24 weeks, and improvement in knee pain (VAS) at 4, 8, 12, 16, and 20 weeks. Intention-to-treat analyses of primary and secondary outcomes will be performed as the primary analyses. Per protocol analyses will be performed as the secondary analyses.DiscussionThis study will provide high-quality evidence to determine whether diacerein improves pain, changes disease trajectory, and slows disease progression in OA patients with effusion-synovitis. If diacerein proves effective, this has the potential to significantly benefit the substantial proportion (up to 60%) of knee OA patients with an inflammatory phenotype.Trial registrationAustralian and New Zealand Clinical Trial Registry ACTRN12618001656224. Registered on 08 October 2018.

Nocturnal pain, is the pain different compared with pain during the day? An exploratory cross-sectional study in patients with hip and knee osteoarthritis.

To explore characteristics of nocturnal pain and to identify differences in participants' characteristics and osteoarthritis (OA) symptoms between hip and knee OA participants with and without nocturnal pain. Data for this exploratory cross-sectional study were obtained from an online survey, distributed through social media and patient associations in the period from April 2020 until May 2020, which was conducted in 101 participants with (self-reported) hip or knee OA. Descriptive statistics were used to provide insight into the characteristics of the study population. Pain intensity, localization, dimension, and impact of (nocturnal) pain on sleep were described and compared with daytime pain. Nocturnal pain was reported by 76/101 (75%) participants. Participants with nocturnal pain scored higher visual analogue scale (VAS) scores for their nocturnal pain compared with their pain at the moment (respectively: median VAS score 49.5 vs. 40.0). Their day pain rating indexes of sensory-discriminative dimension were higher compared with their nocturnal pain. Comparison between participants with and without nocturnal pain showed that participants with nocturnal pain were affected by intermittent, constant, and radiating pain. Pain had more impact on their sleep and they scored their pain at its worst higher compared with participants without nocturnal pain. In participants with nocturnal pain (75%), we found that their VAS pain scores were not in harmony with their pain expressed in words. This study increases awareness of nocturnal pain in OA patients in general practice. More research is needed to provide general practitioners possible interventions for patients with OA and nocturnal pain.

Prospects of a Transdermal Dosage Form (Microneedles) and Justification of the Active Substance Selection for Development of a New Medicine.

Prospects for the development of a transdermal dosage form (DF) based on microneedles were considered. Methods for obtaining such systems, the application areas, and data from the pharmaceutical market were examined. A wide sample of INNs that are used to reduce pain in osteoarthritis patients was formed based on clinical guidelines. The market capacity, sales by Anatomical Therapeutic Chemical (ATC-2) groups, and sales depending on the DF were discussed. Criteria for the choice of active ingredients with market potential were defined. An analysis of a short list revealed that meloxicam has sufficient market potential to create a microneedle DF. A forecast of meloxicam consumption based on time series models indicated stable sales-growth dynamics and a potential market size of 4.6 billion Russian rubles by 2030. Results of the study indicated good market prospects and justification of pharmaceutical development of a new transdermal DF including meloxicam microneedles as the active ingredient.

Associations of osteoclastogenesis and nerve growth in subchondral bone marrow lesions with clinical symptoms in knee osteoarthritis.

Background/objectiveSubchondral bone marrow lesions (BMLs) are common magnetic resonance imaging (MRI) features in joints affected by osteoarthritis (OA), however, their clinical impacts and mechanisms remain controversial. Thus, we aimed to investigate subchondral BMLs in knee OA patients who underwent total knee arthroplasty (TKA), then evaluate the associations of osteoclastogenesis and nerve growth in subchondral BMLs with clinical symptoms.MethodsTotal 70 patients with primary symptomatic knee OA were involved, then separated into three groups based on MRI (without BMLs group, n ​= ​14; BMLs without cyst group, n ​= ​37; BMLs with cyst group, n ​= ​19). Volume of BMLs and cyst-like lesions was calculated via the OsiriX system. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was used to assess clinical symptoms. Histology and immunohistochemistry were deployed to assess subchondral osteoclastogenesis and nerve distribution. Pearson's correlation coefficient was used to evaluate the associations between volume of BMLs and joint symptoms, and to assess the associations of osteoclastogenesis and nerve growth in subchondral BMLs with joint symptoms.ResultsIn BMLs combined with cyst group, patients exhibited increased osteoclastogenesis and nerve distribution in subchondral bone, as shown by increased expression of tartrate resistant acid phosphatase (TRAP) and protein gene product 9.5 (PGP9.5). Volume of subchondral cyst-like component was associated with joint pain (p ​< ​0.05). Subchondral osteoclastogenesis and nerve distribution were positively associated with joint pain in BMLs with cyst group (p ​< ​0.05).ConclusionThe subchondral cyst-like lesion was an independent factor for inducing pain in OA patients; osteoclastogenesis and nerve growth in subchondral cyst-like lesions could account for this joint pain.The translational potential of this articleOur results indicated that the increased osteoclastogenesis and nerve growth in subchondral cyst-like lesions could account for the pain of OA joints. These findings may provide valuable basis for the treatment of OA.

Correlation between CD163 expression and resting pain in patients with hip osteoarthritis: Possible contribution of CD163+ monocytes/macrophages to pain pathogenesis.

Expression of CD163, a scavenger receptor specifically expressed by monocytes and macrophages, is elevated in the synovial tissue of patients with knee osteoarthritis (OA) compared with healthy controls. However, the association between CD163 expression in the synovium and pain in OA patients is unclear. We investigated the correlation between synovial CD163 expression and resting and active pain levels in patients with hip osteoarthritis (HOA). To investigate the possible contribution of CD163+ subsets to pain pathogenesis, we compared pain-related cytokine expression and M1/M2 macrophage marker expression in CD163+ and CD163- cells. We performed flow cytometric analysis to study the CD163+ cell population. We also examined pain-related cytokine expression and M1/M2 macrophage marker expression on CD163+ CD14high and CD163+ CD14low cells using cell sorting. Synovial CD163 expression significantly correlated with resting pain levels (p = 0.006; R = 0.321), but not active pain levels (p = 0.155; R = 0.169). Expression of the M1 macrophage marker CD80 was significantly higher in CD163+ than CD163- cells (p = 0.010), as was the expression of M2 macrophage markers CD206 and IL10 (CD206, p = 0.014; IL10, p = 0.005), and TNFA and IL1B (TNFA, p = 0.002; IL1B, p = 0.001). TNFA expression was significantly higher in CD163+ CD14low than CD163+ CD14high cells, while IL1B, IL10, and CD206 expression were comparable among these subsets. Our findings suggest that CD163 expression is associated with higher resting pain scores. As TNF-α plays a role in the pain process, CD163+ CD14low cells expressing TNFA may be a potent contributor to the pathogenesis of resting pain in HOA.

CD14, A toll-like receptor co-factor, influences osteoclast differentiation and activity, but does not alter osteoblastic potential of bone-marrow preursors in mice

Purpose: Changes in subchondral bone structure occur in osteoarthritis (OA), and are visible by imaging as subchondral sclerosis on radiographs, and bone marrow lesions (BMLs) by MRI. These changes are the result of active bone remodeling that occurs in OA. BMLs in particular are correlated with pain in OA patients. We previously demonstrated that bone remodeling was significantly reduced after joint injury in mice deficient in CD14. CD14 enhances Toll-like receptor (TLR) mediated inflammation by acting as a co-receptor for multiple TLRs, increasing TLR sensitivity to damage associated molecular patterns (DAMPS) to activate proinflammatory signaling pathways. Soluble CD14, TLRs, and DAMPs (TLR ligands) are all elevated in OA patients, and sCD14 has been implicated as a biomarker of symptom and structural severity in OA. Increasing evidence suggestions CD14/TLR signaling influences bone remodeling as well, through activation of osteoclast precursor cells. Here, we investigate the potential mechanism by which CD14 influences bone remodeling through in vitro analysis of osteoclastogenic and osteoblastic potential and function. Methods: Bone marrow (BM) hematopoietic and mesenchymal precursors were isolated from long bones of 12-week-old male wild-type C57BL/6 (WT) and CD14-deficient (CD14-/-) mice. Briefly, BM was flushed from the femurs and tibia, and cells were cultured for 24 hours to separate non-adherent from adherent population. For osteoclastic differentiation, the non-adherent cells were seeded at a density of 26,000 cells per cm2 and were cultured in presence of monocyte/macrophage colony-stimulating factor (M-CSF; 35 ng/ml) and receptor activator of nuclear factor kβ ligand (RANKL; 100 ng/ml) for 9 days. Osteoblastic differentiation was accomplished by seeding the adherent BM cells at 30,000 cells per cm2 and culturing in the presence of 10 mM β-glycerophosphate ,50 μM ascorbic acid, and 100 nM Dexamethasone for up to 19 days. Osteoclasts were identified as multinucleated cells with positive TRAP staining. The resorptive ability of osteoclasts was assayed by quantifying resorption pits formed on bone slices. For osteoblast differentiation, Alizarin red was used to detect mineralized bone matrix. At the completion of each assay RNA was isolated from cultures and Real-time quantitative PCR analysis was performed to detect changes in mRNA levels of osteoclast (i.e. calcitonin receptor/CTR and cathepsin K/Ctsk) and osteoblast (i.e. osteopontin/OPN and osteocalcin/BLAP) differentiation markers. Results: Cells from CD14-/- mice demonstrated decreased percentages of TRAP positive cells and multi-nucleated cells (p value = 0.01; Fig. 1 A-D) and reduced Ctsk mRNA (p value = 0.03; Fig. 1 E&F), compared to WT controls. CD14-/- cells showed a 50% reduction in resorption pits and area compared to WT (Fig. 1 G&I). No significant differences were observed between strains in osteoblastic potential measured by mineralization and gene expression of osteoblastic markers (Fig. 2). Conclusions: CD14-/- BM precursor cells have reduced capacity to differentiate into functional osteoclasts, while osteoblastic potential is retained. This suggests that the reduced capacity of CD14-deficient osteoclastic cells may lead to the reduced bone remodeling in response to joint injury seen in the DMM model, by disrupting the balance between resorption and formation. Future experiments will determine the influence of DAMPs on osteoclast differentiation and activity, and the density of osteoclasts in SCB after DMM injury. These experiments will lead to a better understanding of the role of CD14 and TLR pathways on bone remodeling in response to joint injury and OA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Associations of bone marrow lesions related subchondral osteoclastogenesis and neurogenesis with clinical symptoms in knee osteoarthritis

Purpose: To evaluate the associations of bone marrow lesions (BMLs) (including the subtypes) related subchondral osteoclastogenesis and neurogenesis with clinical symptoms in knee osteoarthritis (OA) patients, and to figure out how subchondral cyst-like lesions caused pain of joint. Methods: Samples were harvested from 33 symptomatic knee OA patients who had underwent total knee arthroplasty (TKA). These patients were separated into three groups based on magnetic resonance imaging (MRI), including group without BMLs (n=6), group has BMLs without cyst-like lesions (n=19), and group has BMLs combined with cyst (n=8). Hematoxylin and eosin (H&E) and O/fast green (S&F) staining were deployed to show subchondral structure and cartilage damage. Tartrate resistant acid phosphatase (TRAP) and protein gene product 9.5 (PGP9.5) staining were applied to detect subchondral osteoclastogenesis and neurogenesis in various groups. Pearson’s correlation coefficient and linear regression analyses were deployed to analyze the relationships between BMLs and knee symptoms, and further to assess the associations of subchondral osteoclastogenesis and neurogenesis with pain of joint. Results: Patients with BMLs combined with cyst-like lesions exhibited necrotic bone fragments in the subchondral bone and increased destruction in the cartilage. Volume of the subchondral cyst-like component itself was significantly associated with pain in OA patients (p<0.05), moreover, it was positively linearly correlated with WOMAC pain score (r2=0.5099, p=0.0466). Subchondral osteoclast density and neurogenesis were significantly increased in group with BMLs combined with cyst compared with the other two groups (p<0.05), and they were positively associated with pain in patients with BMLs combined with cyst (p<0.05). Conclusions: Subchondral cyst was an independent factor for inducing pain of knee OA patients. Subchondral cyst-like lesions related osteoclastogenesis and neurogenesis could cause pain of joint.

Cryoneurolysis for the management of chronic pain in patients with knee osteoarthritis; a double-blinded randomized controlled sham trial

ObjectivePain is the principal symptom in knee osteoarthritis (OA). Current non-operative treatment options have only moderate effects and often patients experience persistent pain or side-effects. Novel advances in the field of cryoneurolysis applies low temperatures to disrupt nerve signaling at the painful area, providing pain relief. The primary aim of this randomized controlled trial (RCT) is to investigate if cryoneurolysis is superior to sham at decreasing pain intensity 2 weeks after the intervention in patients with knee OA. Secondary aims are to explore effects on pain, quality of life and functional performance over 24 months.MethodsThis two-arm, parallel-group RCT, approved by the Regional Ethics Committee, will randomly allocate patients (n = 94) to a cryoneurolysis intervention group + standardized education and exercise (CRYO) or a sham group + standardized education and exercise (SHAM) (1:1 ratio). Both groups will be assessed at baseline, 2 weeks post intervention, post education and exercise and at 6, 12 and 24 months after cryoneurolysis. The primary outcome is the NRS knee pain intensity score assessed 2 weeks post the intervention. Secondary outcome measures include functional performance (chair-stand test, 40 m walk, stair test and maximum voluntary contraction of the knee), patient reported outcomes (quality of life (EQ5D), Knee and osteoarthritis outcome scores (KOOS), among others), use of analgesics, and adverse events over 24 months.Impact statementCryoneurolysis could potentially provide an effective, safe and non-pharmacological therapeutic option to treat pain in OA patients. The potential benefits include increased functional capacity and quality of life as a result of significant pain relief and improved benefits of physical exercise.Trial registrationClinicaltrials.gov, NCT03774121, registered 3 March 2018, http://www.clinicaltrials.gov

The Effectiveness of Exercise Therapy on Reducing Pain in Osteoarthritis Patients: Literature Review

Osteoarthritis (OA) is a chronic joint disorder with damage to the joint cartilage, this causes a decrease in the functional ability and perform daily activities. So intervention is needed in reducing these problems to increase and maintain independence in carrying out training activities. The research will aim to detect the influences of exercises that can be applied to OA patients to reduce pain. This research used a systematic literature study approach obtained from PubMed database and Science Direct. In total, the literature review systematic review concluded that exercise therapy can affect pain in osteoarthritis. The results of this systematic review revealed that yoga improves OA symptoms and can be done safely without supervision at home. In conclusion, the result of this study showed that there were Moderate physical activity at least three times per week can reduce the risk of arthritis-related disability. However, there is increasing evidence in the literature for the beneficial effects of exercise for managing OA. Evidence on the comparative effectiveness of different types of exercise, including exercise adherence and satisfaction in older adults with knee OA, is limited.