Knee Osteoarthritis Pain Research Articles

NGF Signaling Exacerbates KOA Peripheral Hyperalgesia via the Increased TRPV1-Labeled Synovial Sensory Innervation in KOA Rats.

Knee osteoarthritis (KOA) pain is caused by nociceptors, which are actually sensory nerve fiber endings that can detect stimuli to produce and transmit pain signals, and high levels of NGF in synovial tissue led to peripheral hyperalgesia in KOA. The purpose of this study is to investigate how sensory nerve fibers respond to the NGF/TrKA signal pathway and mediate the peripheral hyperalgesia in KOA rats. Forty SD male rats were randomly divided into 4 groups: normal, KOA, KOA + NGF, and KOA + siRNA TrKA. KOA model rats were induced by anterior cruciate ligament transection (ACLT). Mechanical and cold withdrawal thresholds (MWT and CWT) were measured 4 times in each group. The synovial tissues were harvested on day 28, and the expressions of NGF, TrKA, TRPV1, IL-1β, and PGP9.5 were determined using western blot, qPCR, and immunofluorescence staining. The primary rat fibroblast-like synoviocytes (FLSs) and DRG cells were divided into 4 groups as in vivo. The expressions of NGF, TrKA, TRPV1, and CGRP in vitro were determined using western blot and qPCR. KOA and intra-articular injection with NGF protein increased both mRNA and protein levels, not only TRPV1, PGP 9.5, and IL-1β in the synovial tissue, but also TRPV1, PGP 9.5, and S100 in the DRG tissue, while above changes were partly reversed after siRNA TrKA intervention. Besides, siRNA TrKA could improve peripheral hyperalgesia and decreased the TRPV1 positive nerve fiber innervation in synovial tissue. The results in vitro were consistent with those in vivo. This study showed the activation of the NGF/TrKA signaling pathway in KOA promoted the release of pain mediators, increased the innervation of sensory nerve fibers in the synovium, and worsened peripheral hyperalgesia. It also showed increased TRPV1 positive sensory innervation in KOA was mediated by NGF/TrKA signaling and exacerbated peripheral hyperalgesia.

Medial or Lateral, That Is the Question: A Retrospective Study to Compare Two Injection Techniques in the Treatment of Knee Osteoarthritis Pain with Hyaluronic Acid.

Background: Mild-to-moderate knee osteoarthritis (KOA) can be successfully treated using intra-articular hyaluronic acid (IA-HA). The medial infrapatellar (MIP) approach and lateral infrapatellar (LIP) approach are two of the most used techniques for performing IA-HA, but it is still not clear which one is preferable. Objectives: The study aims to find the best knee injection technique between MIP and LIP approaches. Methods: In total, 161 patients were enrolled, divided into two groups (MIP or LIP). Each technique was performed once a week for three weeks. Patients were evaluated using the Numeric Rating Scale (NRS), Knee Injury and Osteoarthritis Outcome Score (KOOS) and Roles and Maudsley Score (RMS) at T0 (before the first injection), T1 (one week after the third injection) and T2 (six months after). Results: NRS, KOOS and RMS showed a statistically significant improvement in both groups at all the detection times, without significant differences. No differences were detected between the groups in terms of systemic effect effusions, while the MIP group presented a mildly higher number of bruises in comparison with the LIP group (p = 0.034). Conclusions: Both the IA-HA techniques are equally effective in measured outcomes. The MIP approach seems to produce some local and transient side effects. So, the choice of the LIP or MIP approach depends on the operator's skill and experience.

Women show a positive response to platelet-rich plasma despite presenting more painful knee osteoarthritis than men.

The purpose of this study was to evaluate the impact of gender on the efficacy of platelet-rich plasma (PRP) in patients with knee osteoarthritis (KOA), comparing their short-term response between men and women. Four hundred-eighteen patients (529 knees) were included. Patients were treated with threeinjections of PRP on a weekly basis. Blood and PRP samples were randomly tested. Patients were asked to complete the knee injury and osteoarthritis outcome score (KOOS) and 12-item short form survey (SF-12), at baseline and 6 months. Success rates were calculated according to a reduction in the pain score of at least 9.3 points [minimal clinically important improvement (MCII)]. Comparative tests and multivariate regression were performed. The PRP had a platelet concentration factor of 2.0X compared to blood levels, with no leucocytes or erythrocytes. KOOS scores showed an increase from baseline to 6 months (p < 0.0001). There was an increase in the physical component summary (PCS) (p < 0.0001) and mental component summary (MCS) (p < 0.01) of the SF-12. The number of knees of women with MCII was 156 out of 262 (59.6%), whereas the number of knees of men was 136 out of 267 (50.9%) (p = 0.0468). Women had worse baseline scores on pain (p = 0.009), PCS (p < 0.0001) and MCS (p < 0.0001). Although the symptomatology generated by KOA was worse in women when compared to men, treatment with repeated injections of PRP was effective, ultimately achieving a higher improvement in women providing comparable final follow-up outcomes between men and women. Level IV.

Exploring Future Horizons in Osteoarthritis Relief: Unveiling the Potential of Slow-Acting Drugs and Innovative Medications

Introduction: &#x0D; The existing treatment options for osteoarthritis (OA) fall short of addressing the significant challenges this disease imposes on patients in today's society. It markedly diminishes the quality of life of those affected and is one of the leading causes of disability. While conventional pharmacological interventions such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioids effectively address pain, they are not intended to halt disease progression and are associated with potential health risks. Symptomatic Slow-Acting Drugs for Osteoarthritis (SYSADOA) and innovative medications, rooted in our expanding understanding of OA pathogenesis, offer promising prospects for discovering improved treatment modalities.&#x0D; &#x0D; State of knowledge: &#x0D; The evolving understanding of OA's etiology highlights the necessity for tailored treatments that consider distinct disease phenotypes. This review critically examines SYSADOA, specifically focusing on chondroitin sulfate, glucosamine, and avocado-soybean unsaponifiables, as agents designed to address the underlying pathology of OA. Chondroitin sulfate demonstrates potential disease-modifying effects, however with conflicting study results that underscore the extent of its efficacy. Glucosamine exhibits varying disease-modifying effects, with short-term trials demonstrating more promising outcomes in pain reduction. Avocado-soybean unsaponifiables show promise in alleviating knee OA pain, yet their impact on hip OA symptoms remains inconclusive. The review extends its scope to novel drugs with potential disease-modifying effects, exploring proteinase inhibitors, fibroblast growth factors, Wnt-signaling pathway inhibitors, senolytic agents, anti-nerve growth factor agents, and transforming growth factor-β.&#x0D; &#x0D; Conclusions: &#x0D; Although preliminary studies indicate potential for certain novel agents, challenges and adverse effects necessitate further investigation through rigorous, high-quality research.

Does the Combination of Platelet-rich Plasma and Supervised Exercise Yield Better Pain Relief and Enhanced Function in Knee Osteoarthritis? A Randomized Controlled Trial.

Knee osteoarthritis is a leading cause of disability with substantial healthcare costs, and efficient nonsurgical treatment methods are still needed. Platelet-rich plasma (PRP) injections and exercise therapy are used frequently in clinical practice. Whether PRP or PRP combined with exercise is more effective than exercise alone is unclear. (1) Which treatment relieves knee osteoarthritis pain better: PRP alone, exercise, or PRP combined with exercise? (2) Does PRP alone, exercise, or PRP combined with exercise yield better results in terms of the WOMAC score, performance on the 40-m fast-paced walk test and stair climbing test, and the SF-12 health-related quality of life score? In this randomized, controlled, three-arm clinical trial, we recruited patients with mild-to-moderate (Kellgren-Lawrence Grade II or III) knee osteoarthritis with a minimum of 3 points on the 11-point numeric rating scale for pain. During the study period, 157 patients with a diagnosis of knee osteoarthritis were screened and 84 eligible volunteers were enrolled in the study. Patients were randomly allocated (1:1:1) into either the exercise group (28), PRP group (28), or PRP + exercise group (28). Follow-up proportions were similar between the groups (exercise: 89% [25], PRP: 86% [24], PRP + exercise: 89% [25]; p = 0.79). All patients were analyzed in an intention-to-treat manner. There were no between-group differences in age, gender, arthritis severity, and baseline clinical scores (pain, WOMAC, functional performance tests, and health-related quality of life). The exercise group underwent a 6-week structured program consisting of 12 supervised individual sessions focused on strengthening and functional exercises. Meanwhile, the PRP group received three weekly injections of fresh, leukocyte-poor PRP. The PRP + exercise group received a combined treatment with both interventions. The primary outcome was knee pain over 24 weeks, measured on an 11-point numeric rating scale for pain (ranging from 0 to 10, where 0 represents no pain and 10 represents the worst pain, with a minimum clinically important difference [MCID] of 2). The secondary outcome measures included the WOMAC index (ranging from 0 to 100, with lower scores indicating a lower level of disability and an MCID of 12), the durations of the 40-meter fast-paced walk test and stair climbing test, and the SF-12 health-related quality of life score. For the a priori sample size calculation, we used the numeric rating scale score for pain at 24 weeks as the primary outcome variable. The MCID for the numeric rating scale was deemed to be 2 points, with an estimated standard deviation of 2.4. Based on sample size calculations, a sample of 24 patients per group would provide 80% power to detect an effect of this size between the groups at the significance level of p = 0.05. We found no clinically important differences in improvements in pain-defined as ≥ 2 points of 10-at 24 weeks when comparing exercise alone to PRP alone to PRP + exercise (1.9 ± 0.7 versus 3.8 ± 1.8 versus 1.4 ± 0.6; mean difference between PRP + exercise group and exercise group -0.5 [95% confidence interval -1.2 to 0.4]; p = 0.69). Likewise, we found no differences in WOMAC scores at 24 weeks of follow-up when comparing exercise alone to PRP alone to PRP + exercise (10 ± 9 versus 26 ± 20 versus 7 ± 6; mean difference between PRP + exercise group and exercise group -3 [95% CI -12 to -5]; p = 0.97). There were no differences in any of the other secondary outcome metrics among the PRP + exercise and exercise groups. PRP did not improve pain at 24 weeks of follow-up in patients with mild-to-moderate knee osteoarthritis compared with exercise alone. Moreover, exercise alone was clinically superior to PRP alone, considering function and the physical component of health-related quality of life. Despite the additional costs and endeavors related to PRP products, the combination of PRP and exercise did not differ from exercise alone. The results of this randomized controlled trial do not support the use of PRP injections in the treatment of patients diagnosed with mild-to-moderate knee osteoarthritis. Consequently, exercise alone is the recommended treatment for reducing pain and enhancing function throughout this timeframe. Level I, therapeutic study.

Pathology of knee osteoarthritis pain: contribution of joint structural changes and pain sensitization to movement-evoked pain in knee osteoarthritis.

Movement-evoked pain (MEP) is the primary symptom in patients with knee osteoarthritis (KOA). This study aimed to investigate the contribution of joint structural changes and pain sensitization to the mechanisms of MEP in patients with KOA. A total of 86 patients were assessed for demographic characteristics, osteoarthritis severity, Whole-Organ Magnetic Resonance Imaging Score-Hoffa synovitis and bone marrow lesions, pressure pain threshold and temporal summation of pain at the knee and forearm, Central Sensitization Inventory-9, and MEP. In measure of MEP, knee pain was scored using a numerical rating scale (NRS, 0-10) before and every minute during a 6-minute walking test (6MWT), and the MEP index was defined as the change in NRS pain score from baseline to the sixth minute of walking. On average, pain during 6MWT increased by 1.4 ± 1.5 points on the NRS relative to baseline, with 30.2% of patients showing an increase of 2 points or more. The hierarchical linear regression analysis revealed that Hoffa synovitis, pressure pain threshold at the forearm, and temporal summation of pain at the knee were associated with the MEP index. The findings of this study suggest that both synovitis and neural mechanisms, such as pain sensitization, play a role in the development of MEP in KOA.

Is acupuncture combined with usual medical care more effective than usual medical care alone for the treatment of knee osteoarthritis pain?

Is acupuncture combined with usual medical care more effective than usual medical care alone for the treatment of knee osteoarthritis pain?

Effect of nerve growth factor on elderly degenerative knee osteoarthritis pain

To explore effect of nerve growth factor (NGF) antibody on knee osteoarthritis (KOA) pain model was evaluated by in vitro model. Thirty male SPF rats aged 28-week-old were divided into blank group (10 rats with anesthesia only). The other 20 rats were with monoiodoacetate (MIA) on the right knee joint to establish pain model of OA, and were randomly divided into control group (injected intraperitoneal injection of normal saline) and treatment group (injected anti-NGF) intraperitoneal after successful modeling, and 10 rats in each group. All rats were received retrograde injection of fluorogold (FG) into the right knee joint. Gait was assessed using catwalk gait analysis system before treatment, 1 and 2 weeks after treatment. Three weeks after treatment, right dorsal root ganglia (DRG) were excised on L4-L6 level, immunostained for calcitonin gene-related peptide (CGRP), and the number of DRGS was counted. In terms of gait analysis using cat track system, duty cycle, swing speed and print area ratio in control and treatment group were significantly reduced compared with blank group (P<0.05). Compared with control group, duty cycle and swing speed of treatment group were significantly improved (P<0.05), and there was no significant difference in print area ratio between treatment group and blank group (P>0.05). The number of FG-labeled DRG neurons in control group was significantly higher than that in treatment group and blank group (P<0.05). The expression of CGRP in control group was up-regulated, and differences were statistically significant compared with treatment group (P<0.05). Intraperitoneal injection of anti-NGF antibody inhibited gait injury and upregulation of CGRP in DRG neurons. The results suggest that anti-nerve growth factor therapy may be of value in treating knee pain. NGF may be an important target for the treatment of knee OA pain.

Confirmation of pain-related neuromodulation mechanism of Bushen Zhuangjin Decoction on knee osteoarthritis

Ethnopharmacological relevanceBushen Zhuangjin Decoction (BZD) are an herbal compound commonly used to treat osteoarthritis (OA) in China. Aim of the studyThis study aimed to verify the mechanism of Bushen Zhuangjin Decoction in relieving the pain of knee osteoarthritis. Materials and methodsNetwork pharmacology evaluation was used to discover the potential targets of BZD to relieve pain in KOA. The therapeutic effects of BZD treatment on KOA pain using histomorphology, behavioral assessments, suspension chip analysis, and ultra-high performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) assays. The functional magnetic resonance imaging was used to explore the effects of BZD treatment on brain function associated to KOA. ResultsNetwork pharmacological analysis revealed the association between the analgesic effect of BZD on KOA and the pain signaling neurotransmitter 5-HT. Subsequently, we conducted experiments to verify the therapeutic effect of BZD on pain in KOA animal models. Behavioral tests demonstrated that the pain threshold of knee osteoarthritis rats decreased in PWT and PWL, but BZD was able to increase the pain threshold. Histopathological staining indicated thinning of the cartilage layer and sparse trabeculae in the subchondral bone. Suspension chip analysis revealed a significant increase in pro-inflammatory factors of IL-1α, IL-5, IL-12, IL-17A, RANTES, TNF-α and M-CSF in KOA, along with a significant decrease in anti-inflammatory factor of IL-13. However, BZD treatment decreased the expression of pro-inflammatory factors and increased the content of anti-inflammatory factor. UHPLC-MS/MS analysis showed a significant decrease in the serum levels of GABA, E, GSH, Kyn, Met, and VMA in KOA, which were significantly increased by BZD. Conversely, the serum levels of TrpA, TyrA, Spd, and BALa were significantly increased in KOA and significantly decreased by BZD. ELISA and Western blot analysis showed increased expression of subchondral bone pain-related neuropeptides SP, CGRP, TH, NPY, VEGFA, 5-HT3 in KOA, which were decreased in BZD. Functional magnetic resonance imaging demonstrated that BZD exerts its therapeutic effect on KOA by modulating the activity and functional connections of the cortex, hypothalamus, and hippocampus. ConclusionsThis study confirmed the significant role of pain-related neuromodulation mechanisms in the analgesic therapy of BZD and provides a theoretical foundation for using BZD as a traditional Chinese medical treatment for KOA pain.

Tetraspanin profiles of serum extracellular vesicles reflect functional limitations and pain perception in knee osteoarthritis.

Emerging evidence suggests that extracellular vesicles (EVs) can play roles in inflammatory processes and joint degradation in primary osteoarthritis (OA), a common age-associated joint disease. EV subpopulations express tetraspanins and platelet markers that may reflect OA pathogenesis. The present study investigated the associations between these EV surface markers and articular cartilage degradation, subjectively and objectively assessed pain, and functional limitations in primary knee OA (KOA). Serum EVs were determined by high-sensitivity flow cytometry (large CD61+ EVs) and single particle interferometric reflectance imaging sensor (small CD41+, CD63+, CD81+, and CD9+ EVs) from end-stage KOA patients and controls (n = 8 per group). Knee pain and physical functions were assessed with several health- and pain-related questionnaires, established measurements of physical medicine, and neuromuscular examination. The obtained data were analyzed using supervised and unsupervised univariate and multivariate models. With the combined dataset of cartilage thickness, knee function, pain, sensation, and EV molecular signatures, we identified highly correlated groups of variables and found several EV markers that were statistically significant predictors of pain, physical limitations, and other aspects of well-being for KOA patients, for instance CD41+/CD63+/CD9+ small EVs associated with the range of motion of the knee, physical performance, and pain sensitivity. Particular serum EV subpopulations showed clear associations with KOA pain and functional limitations, suggesting that their implications in OA pathophysiology warrant further study.

Effect of Partial Blood Flow Restriction Training in Improving Physical Functioning among Middle-Aged Subjects with Knee Osteoarthritis: A Pilot Study

Background: Blood Flow Restriction (BFR) training combines low-intensity exercise with blood flow occlusion toproduce outcomes comparable to those of high-intensity training. BFR is as effective as high-intensity protocolsknown to enhance knee extensor muscle strength in subjects with knee osteoarthritis (OA). Therefore, the aimof this study is to find out the effect of Partial Blood Flow Restriction Training on pain and physical functioningamong knee OA subjects.Purpose: To assess the effectiveness of Partial Blood Flow Restriction Training in Improving Physical FunctioningAmong Middle-Aged Subjects with Knee Osteoarthritis.Materials and Methods: This is the pilot study where twenty subjects with knee OA were divided randomly intotwo equal groups. Group “A” received BFR training combined with conventional exercise two times/week andGroup “B” received conventional exercise two times/week. Numeric Pain Rating Scale (NPRS), Western Ontarioand McMaster Universities Arthritis Index (WOMAC) were used to evaluate subjects at two intervals (Pre-Testand Post-Test).Results: The difference between the Group A and Groups B was statistically significant (p&lt;=0.001). Henceconventional exercise combined with blood flow restriction training shows significant improvement thanconventional exercise among OA knee subjects.Conclusion: This pilot study concluded that the conventional exercise combined with blood flow restrictiontraining was effective in subjects with OA knee.

Alleviation of peripheral sensitization by quadriceps insertion of cog polydioxanone filaments in knee osteoarthritis rats

A recently established therapeutic strategy, involving the insertion of biodegradable cog polydioxanone filaments into the quadriceps muscles using the Muscle Enhancement and Support Therapy (MEST) device, has demonstrated significant efficacy in alleviating knee osteoarthritis (OA) pain. This study investigated changes in peripheral sensitization as the potential mechanism underlying MEST-induced pain relief in monoiodoacetate (MIA) induced OA rats. The results revealed that MEST treatment potently reduces MIA-induced sensitization of L3/L4 dorsal root ganglion (DRG) neurons, the primary nociceptor pathway for the knee joint. This reduction in DRG sensitization, as elucidated by voltage-sensitive dye imaging, is accompanied by a diminished overexpression of TRPA1 and NaV1.7, key nociceptor receptors involved in mechanical pain perception. Importantly, these observed alterations strongly correlate with a decrease in mechanically-evoked pain behaviors, providing compelling neurophysiological evidence that MEST treatment alleviates OA pain by suppressing peripheral sensitization.

Prevalence of Knee OA and its Association with Low Back Pain

Background: Knee osteoarthritis (OA) is a prevalent musculoskeletal condition known to impact quality of life and daily functioning significantly. Previous studies have identified a potential association between knee OA and low back pain, but this relationship requires further exploration to understand its implications fully. Objective: The objective of this study was to investigate the correlation between knee OA and low back pain, specifically examining the impact of knee pain on quality of life, daily functioning, and the severity of low back pain. Methods: A cross-sectional study was conducted with 377 OA patients aged between 45 to 75 years, selected via non-probability convenient sampling from various hospitals in Sialkot. Exclusion criteria included a history of knee surgery or recent trauma, mental retardation, or diabetes. Data were collected using the Oswestry Low Back Disability Index and the KOOS Urdu version. Statistical analysis was performed using SPSS version 26, focusing on descriptive statistics, mean and standard deviation for quantitative data, and the chi-square test for associations, with a significance threshold set at a p-value greater than 0.05. Results: The study found that the prevalence of knee OA varied by age group, with the highest prevalence (46.6%) in the 45-54 age group. Female participants predominated (75.9%). Severity levels of knee OA were classified as mild (32.6%), moderate (42.2%), and severe (21.8%). Significant correlations were observed between knee OA and low back pain, with correlation coefficients of 0.480 for pain effects on QOL, 0.441 for pain during SRF, 0.571 for pain during AODL, and 0.437 for the total score of pain. Conclusion: The study confirms a significant correlation between knee OA and low back pain, highlighting the need for integrated management approaches for patients suffering from these conditions. Addressing both knee and back pain concurrently could lead to better patient outcomes and improved quality of life.

An evaluation of knee osteoarthritis pain in the general community-Asir region, Saudi Arabia.

Knee osteoarthritis (KOA) is one of the most common conditions resulting in disability, particularly in the elderly population. Osteoarthritis (OA) is the most common articular disease and the leading cause of chronic disability in the developed world. This study was carried out to evaluate knee pain in the Asir region of Saudi Arabia. An analytical cross-sectional survey design was adopted in the Asir region from April 2023 to August 2023 to assess the knee pain of the adult population using an anonymous online questionnaire. Of 1234, 332 were men (26.90) and 902 were women (73.09). WOMAC index score category 55.34% (n = 683) of the subjects had a low risk (score <60), 28.68% (n = 354) had a moderate risk (score 60-80), and 15.96% (n = 197) had a high risk (score ≥81) for KOA. According to clinical criteria, 79.33% (n = 979) of the study subjects had OA. Age group, gender 2.17 (1. 67-2.82) [OR 2.17; 95% CI 1.67-2.82), family history of OA [OR 0.47; 95% CI 0.37-0.62], diabetes [OR 2.78; 95% CI 2.17-3.56], hypertension [OR 0.35; 95% CI 0.26-0.45] were significantly associated with the percentage of the WOMAC index score using the Chi-square test analysis (P<0.05). Therefore, the WOMAC index showed higher diagnostic precision with a statistically significant association [OR 9.31 CI 6.90-12.81] with a P< 0.0001. KOA is more common in older, obese people who have reached the age of 50 in the Asir region, and it is more prevalent in women. Alarms the need for appropriate awareness programs for better disease prevention and health outcomes for the benefit of the community through general public health programs.

Effect of Transdermal Microneedle Patch Plus Nonsteroidal Anti-Inflammatory Drug in Knee Osteoarthritis: A Randomized, Double-Blind Study

Purpose: No recent clinical study has shown the efficacy of transdermal microneedle patch (TDM) plus nonsteroidal antiinflammatory drug (NSAID) in early knee osteoarthritis (OA). This study aimed to determine the effect of TDM plus NSAID on synovial hypertrophy, knee pain, and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score in osteoarthritic knees. Methods: A randomized, controlled, double-blind trial was conducted. One hundred participants, aged 40–70 years, with painful knee OA and radiographic nonstructural changes were randomly assigned into two groups to undergo TDM plus NSAID (ketorolac 30 mg) or TDM (placebo) at the medial joint line of the knee twice (once weekly). The synovial thickness was measured using ultrasonography at pretreatment, weeks 1, 2, and 4. The visual analog scale (VAS) for pain, WOMAC score, and adverse events (AEs) were also recorded. Results: The TDM plus NSAID group demonstrated a significant reduction in synovial thickness and VAS at weeks 2 and 4 compared with the placebo group (P&lt;0.05). At week 4, the mean synovial thickness reduction was 1.1 and 0.3 mm, and the mean VAS reduction was 3.2 and 1.7 for the TDM plus NSAID and placebo groups, respectively. The mean WOMAC scores at week 4 were significantly reduced (5.7 and 0.9 for the TDM plus NSAID and placebo groups, respectively). No complication and treatment-related AEs occurred. Conclusions: TDM plus NSAID significantly reduced synovitis and improved the pain score in knee OA after 2 weeks. The WOMAC score improved at week 4 without any AEs. Thai Clinical Trials Registry (TCTR), TCTR identification number is TCTR20200613001.

Improving muscle capacity utilization with a 12-week strengthening program for females with symptomatic knee osteoarthritis

BackgroundStrengthening exercise improves symptoms in knee osteoarthritis (OA), but it remains unclear if biomechanical mechanisms contribute to this improvement. Muscle capacity utilization, which reflects the proportion of maximum capacity required to complete tasks, may provide insight into how strengthening exercise improves clinical outcomes in painful knee OA. PurposeThe purpose of this secondary analysis was to determine if a 12-week strengthening intervention reduced muscle capacity utilization during walking, squat and lunge tasks in females with painful knee OA. MethodsData from 28 females (age 59.6 ± 6.2 years old; body mass index 29.1 ± 4.7 kg/m2) with clinical knee OA were included. Participants completed a strengthening intervention 3 times per week for 12 weeks. Knee extensor isometric torque was measured on a commercial dynamometer; peak values from three exertions were averaged. Peak KFM was extracted and averaged from five walking trials. Mean KFM was extracted and averaged from three trials for each of static lunges and squats. Muscle capacity utilization was the ratio of mean peak KFM to peak extensor torque for walking; and mean KFM to peak extensor torque for squats and lunges. Paired t-tests determined differences between peak extensor torque, peak KFM and muscle capacity utilization from pre to post intervention (p < 0.05). Results & significancePeak extensor torque increased at follow up (p = 0.02). Peak KFM during walking decreased (p = 0.005). Muscle capacity utilization during walking (p = 0.008) and squat (p = 0.002) decreased. Mean KFM and muscle capacity utilization during lunge remained unchanged from pre to post intervention. The reduction in muscle capacity utilization at follow up indicates the strengthening intervention produced a decrease in proportion of the maximal capacity a participant used to complete walking and squat tasks. Strengthening both increases maximal muscle capacity and decreases the net moment required during daily tasks in knee OA.

Tai-Chi Exercise Training And Its Promising Therapeutic Impacts Among Older Community Dwelling Adults With Painful Knee Osteoarthritis

Knee joint osteoarthritis, a chronic condition resulting in considerable disability, particularly in later life, not only impacts life quality significantly and severely, but is also strongly associated with the persistence of intractable pain, depression, helplessness, and a high falls injury risk. This narrative overview synthesizes the knowledge base regarding painful knee osteoarthritis and what is known about Tai Chi exercise participation in the context of reducing knee joint disability and its associated risk of one or more injurious falls, as well as pain and depression. To this end, all relevant articles published in the English language on the topic were sought. While most reports rely on Eastern observations, rather than Western medicine studies, collectively, these data reveal that Tai Chi practiced widely in Asia for many centuries may have an enormous positive impact on reducing distress and increasing function and autonomy among older adults living in the community and diagnosed as having knee osteoarthritis. They specifically suggest the increasing numbers of older adults diagnosed as having knee osteoarthritis can safely practice selected Tai Chi exercises with the expectation that consistent applications will enhance mobility, reduce pain and depression, plus instability and possible injurious falls, while reducing fatigue, even if surgery is forthcoming.

Mitonuclear epistasis involving TP63 and haplogroup Uk: Risk of rapid progression of knee OA in patients from the OAI

To investigate genetic interactions between mitochondrial deoxyribonucleic acid (mtDNA) haplogroups and nuclear single nucleotide polymorphisms (nSNPs) to analyze their impact on the development of the rapid progression of knee osteoarthritis (OA). A total of 1095 subjects from the Osteoarthritis Initiative, with a follow-up time of at least 48-months, were included. Appropriate statistical approaches were performed, including generalized estimating equations adjusting for age, gender, body mass index, contralateral knee OA, Western Ontario and McMaster Universities Osteoarthritis Index pain, previous injury in target knee and the presence of the mtDNA variant m.16519C. Additional genomic data consisted in the genotyping of Caucasian mtDNA haplogroups and eight nSNPs previously associated with the risk of knee OA in robust genome-wide association studies. The simultaneous presence of the G allele of rs12107036 at TP63 and the haplogroup Uk significantly increases the risk of a rapid progression of knee OA (odds ratio=1.670; 95% confidence interval [CI]: 1.031-2.706; adjusted p-value=0.027). The assessment of the population attributable fraction showed that the highest proportion of rapid progressors was under the simultaneous presence of the G allele of rs12107036 and the haplogroup Uk (23.4%) (95%CI: 7.89-38.9; p-value<0.05). The area under the curve of the cross-validation model (0.730) was very similar to the obtained for the predictive model (0.735). A nomogram was constructed to help clinicians to perform clinical trials or epidemiologic studies. This study demonstrates the existence of a mitonuclear epistasis in OA, providing new mechanisms by which nuclear and mitochondrial variation influence the susceptibility to develop different OA phenotypes.

Association between niacin intake and knee osteoarthritis pain and function: a longitudinal cohort study.

This research investigates the relationship between niacin intake and knee osteoarthritis (OA) severity, focusing on pain and functional ability due to niacin's role as a NAD(P)+ precursor, promoting cellular energy, and offering anti-inflammatory, analgesic, and antioxidant effects. The population-based Osteoarthritis Initiative (OAI) cohort with radiographically confirmed knee OA was analyzed through a Food Frequency Questionnaire determining niacin intake and scores from the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), using generalized additive mixed models. A significant correlation was pinpointed in 2375 OA patients (1001 men and 1374 women; 55.96% aged between 45 and 65 and 44.04% aged ≥65) between niacin intake and reduced knee pain and functional degrees after a 48-month follow-up, evident in improved KOOS and WOMAC scores (P < 0.05). The fully adjusted models estimated a decrease of 0.26 points for every additional 1 unit of Ln-niacin intake of daily niacin intake on the WOMAC pain subscale, 0.83 points on the WOMAC function subscale, and an increase of 1.71 and 1.58 on the KOOS pain and quality of life score. Strikingly, subgroups including middle-aged individuals, women, white race, obese individuals, and those with specific dietary habits showed a more substantial improvement with increased niacin. The association between increased niacin intake and reduced pain and function scores, as well improved quality of life in knee OA patients, is significant. Certain cohorts, according to a stratified analysis, could see more considerable benefits with increased niacin consumption. • Increased niacin intake is linked to reduced knee pain and better function in OA patients. • Specific subgroups, such as middle-aged individuals, women, and those with certain dietary habits, benefit more from increased niacin consumption. • Niacin shows promise for enhancing the quality of life in knee OA patients by reducing pain and improving function.

Effectiveness and mechanism of action of rTMS combined with quadriceps strength training in individuals with knee osteoarthritis: study protocol for a randomized controlled trial

BackgroundQuadriceps training is necessary in function and activity of daily living for patients with knee osteoarthritis (KOA). However, it did not reduce the rate of surgical treatment for end-stage KOA in the long term. This may be related to brain structure changes and maladaptive plasticity in KOA patients. Transcranial Magnetic Stimulation (TMS) could enhance the functional connectivity of brain regions and improves maladaptive plasticity. However, the synergistic effect of the combination of the two for treat KOA is still unclear. Therefore, the purpose of this study is to investigate whether the High-Frequency rTMS combined with quadriceps strength training can improve the pain and function in KOA more effectively than quadriceps training alone and explore the mechanism of action.MethodsThis study is an assessor-blind, sham-controlled, randomized controlled trial involving 12 weeks of intervention and 6 months follow-up. 148 participants with KOA will receive usual care management and be randomized into four subgroups equally, including quadriceps strength training, high-frequency rTMS training, sham rTMS and quadriceps strength training, high-frequency rTMS and quadriceps strength training. The rehabilitation interventions will be carried out 5 days per week for a total of 12 weeks. All outcomes will be measured at baseline, 4 weeks, 8 weeks, and 12 weeks during the intervention and 1 month, 3 months and 6 months during the follow-up period. The effectiveness outcomes will be included visual analog scale, isokinetic knee muscle strength, Knee Injury and Osteoarthritis Outcome score and 36-Item Short-Form Health Survey score; The act mechanism outcomes will be included motor evoked potential, grey matter density, white matter, subcortical nuclei volumes, cortical thickness and functional connectivity by MRI. Two-way of variance with repeated measures will be used to test the group and time effect for outcome measures.DiscussionThe study will be the first protocol to examine whether there are synergistic effects following high-frequency rTMS combined with quadriceps strength training for treat KOA and clarify the mechanism of action. High-frequency rTMS can be added into the training program for KOA patients if it is proven effective.Trial registrationChinese Clinical Trial Registry ChiCTR2300067617. Registered on Jan.13,2023.