Pain Relief In Osteoarthritis Research Articles

Intraarticular hip corticosteroid injections offer no meaningful benefit in delaying time to total hip arthroplasty in patients with hip osteoarthritis

IntroductionSymptomatic hip osteoarthritis (OA) causes significant morbidity and functional limitations. While corticosteroid injections (CSI) are commonly offered and administered for OA pain relief, it is unknown if they offer any clinically meaningful long-term benefit or reduce the overall need for surgical intervention.MethodsA cross-sectional retrospective cohort study was performed on primary hip osteoarthritis patients from a single academic tertiary-care center arthroplasty clinic from 2014 to 2019. Patients were divided into three groups. CSI + THA: hip CSI patients who underwent subsequent ipsilateral THA. CSI-noTHA: hip CSI who have not had ipsilateral THA to date. THA-noCSI: a control group of consecutive hip OA patients who underwent primary THA without prior CSI. Demographic variables, injection relief duration, and radiographic arthritis severity were recorded. Time from clinic presentation to injection and/or THA were compared.Results357 patients met inclusion criteria and underwent guided, arthroplasty provider-ordered CSI. Mean duration of relief was 6.7 weeks (SD 8.7). 244 injection patients (67.2%) subsequently underwent THA (CSI + THA). 150 of 390 patients have not undergone THA at mean of 25.5 months follow-up. Mean time from clinic presentation to THA was 8.6 months longer after CSI (16.3, SD 17.8) months in CSI patients compared to 7.7 (SD 10.6) months for patients without CSI (p < 0.001). Of 117 patients in the CSI-noTHA group at mean 25 months follow-up, only 43 (12% of all injection patients) had not had THA because they found injections effective. The remaining 74 (63%) of CSI-noTHA patients have been deemed medically unfit for surgery or are currently scheduled for THA.Discussion/ConclusionThe results of this study suggest the utilization of intra-articular CSI as conservative treatment in an arthroplasty clinic does not prolong time to THA for a clinically important duration. The use of CSI should be reserved for diagnostic purposes and/or short-term pain relief in poor surgical candidates.Level of evidenceIII.

Cryoterapy and Ultrasoundtherapy on Pain Relief in Osteoarthritis of Knee Patients with Different Pain Intensities

Cryoterapy and Ultrasoundtherapy on Pain Relief in Osteoarthritis of Knee Patients with Different Pain Intensities

Role of Nigella sativa L. in the Management of Osteoarthritis: A Systematic Review

Because of the anti-inflammatory properties of thymoquinone (TQ), as the main bioactive substance of Nigella sativa L., this systematic review aimed at assessing the therapeutic effects of N. sativa and its main bioactive substance in the management of patients with osteoarthritis (OA) based on the in vivo, in vitro, and in clinical studies. The methodology was adjusted based on the Cochrane Handbook recommendations. All published articles focusing on N. sativa as a therapeutic agent for the treatment of OA or its animal model were searched up to 20 April 2022 in PubMed, Medline, Web of Sciences, and Scopus databases. The search process was carried out using the following keywords: "Nigella sativa", "Black seed', "Black cumin", and "Thymoquinone" in combination with "Osteoarthritis". Finally, 14 articles remained, including five intervention clinical trial, two human studies, and seven animal studies. Four of five intervention studies showed that N. sativa administration led to relief in pain intensity. In the other clinical trial, no difference was reported between the N. sativa and control groups in terms of pain relief among OA patients. Studies demonstrated the anti-inflammatory and chondroprotective effects of TQ as the main bioactive substance of N. sativa. The evidence confirmed the anti-inflammatory and chondroprotective effects of N. sativa in the management of OA patients. Considering the lack of significant adverse effects such as allergic reaction to N. sativa in the aforementioned studies, this substance can be recommended as a safe adjuvant treatment to relieve OA pain, compared to nonsteroidal anti-inflammatory drugs and other analgesics.

Rehmannia alcohol extract inhibits neuropeptide secretion and alleviates osteoarthritis pain through cartilage protection

Osteoarthritis (OA) is a common joint disease characterized by chronic pain, and the perception of pain is closely associated with brain function and neuropeptide regulation. Rehmannia is common plant herb with anti-inflammatory and analgesic properties that is used to treat OA. However, it is unclear whether Rehmannia alleviates OA-related pain via regulation of neuropeptides and brain function. We examined the pain relief regulatory pathway in OA after treatment with Rehmannia by verifying the therapeutic effect of Rehmannia alcohol extract in vivo and vitro and exploring of the potential mechanism underlying the analgesic effect of Rahmanian using functional magnetic resonance imaging and measuring neuropeptide secretion. Our results showed that Rehmannia alcohol extract and the related active ingredient, Rehmannioside D, can delay cartilage degradation and alleviate inflammation in OA rats. The Rehmannia alcohol extract can also relieve OA pain, reduce the secretion of calcitonin gene-related peptide (CGRP) and substance P (SP), and reverse the pathological changes in the cerebral cortex and hippocampus. Our research results demonstrate that Rehmannia alleviates OA pain by protecting cartilage, preventing the stimulation of inflammatory factors on neuropeptide secretion, and influencing the relevant functional areas of the brain.

Comparison of the Effectiveness between Oral NSAIDs and Dextrose Prolotherapy in Knee Osteoarthritis

Non-steroidal anti-inflammatory drugs (NSAIDs) are the first treatment choice for pain relief in osteoarthritis (OA). However, known to have an 85% risk of side effects on the gastrointestinal and a 40% chance of cardiovascular complications. In addition, in certain classes of NSAIDs, the risk of chronic kidney disease increases due to long-term consumption. On the other hand, dextrose prolotherapy is a regenerative therapy. This study aimed to compare the effectiveness of oral NSAIDs with dextrose prolotherapy in knee OA based on clinical features. This study used an observational method (cross-sectional) conducted in three locations; Jember Clinic Hospital, Balung Hospital, and Harapan Mulya Kertonegoro Jenggawah Clinic from September 2021 to March 2022. Of the 75 population, 23 patients with mild to moderate knee OA were divided into two groups; 15 samples of dextrose prolotherapy and eight samples of oral NSAIDs. Data in the study showed the mean WOMAC score in the dextrose prolotherapy group was 12.4±11.7, while the oral NSAID group was 34.75±17.6. A total of 14 samples experienced a decrease in scores after switching from oral NSAIDs to dextrose prolotherapy. Bivariate analyses were performed using Mann-Whitney and Wilcoxon tests. Both statistical tests show a p=0.001 (p&lt;0.05). Thus, this study concluded that dextrose prolotherapy was more effective than oral NSAIDs in knee OA.

Sustained release of locally delivered celecoxib provides pain relief for osteoarthritis: a proof of concept in dog patients

Drug delivery platforms that allow for gradual drug release after intra-articular administration have become of much interest as a treatment strategy for osteoarthritis (OA). The aim of this study was to investigate the safety and efficacy of an intra-articular sustained release formulation containing celecoxib (CXB), a cyclooxygenase-2 (COX-2) selective inhibitor. Amino acid-based polyesteramide microspheres (PEAMs), a biodegradable and non-toxic platform, were loaded with CXB and employed in two in vivo models of arthritis: an acute inflammatory arthritis model in rats (n=12), and a randomized controlled study in chronic OA dog patients (n=30). In parallel, the bioactivity of sustained release of CXB was evaluated in monolayer cultures of primary dog chondrocytes under inflammatory conditions. Sustained release of CXB did not alleviate acute arthritis signs in the rat arthritis model, based on pain measurements and synovitis severity. However, in OA dog patients, sustained release of CXB improved limb function as objective parameter of pain and quality of life based on gait analysis and owner questionnaires. It also decreased pain medication dependency over a 2-month period and caused no adverse effects. Prostaglandin E2 levels, a marker for inflammation, were lower in the synovial fluid of CXB-treated dog OA patients and in CXB-treated cultured dog chondrocytes. These results show that local sustained release of CXB is less suitable to treat acute inflammation in arthritic joints, while safe and effective in treating pain in chronic OA in dogs.

Curcuma longa and Boswellia serrata extract combination for hand osteoarthritis: an open-label pre-post trial

Context Osteoarthritis (OA) of the hand is a common painful musculoskeletal disorder with no cure. There is a need for an efficient and safe treatment to relieve OA pain. Objective To investigate the effects of a Curcuma longa and Boswellia serrata food supplement in addition to standard care on hand pain. Materials and methods This open-label, non-controlled, post-observational study was based on 232 patients suffering from hand pain with or without joint deformity. Patients received a medical prescription for a three-month treatment with a food supplement containing 89 mg of C. longa dry extract, 120 mg of B. serrata resin, and 1.8 µg vitamin D. Pain was evaluated on a 10-point visual analog scale (VAS). The number of painful hand joints, patient satisfaction, nonsteroidal anti-inflammatory drugs intake, and side effects were also recorded. Results Baseline pain intensity (regression coefficient ± SE: −0.19 ± 0.01, p < 0.0001) and the number of painful joints (regression coefficient ± SE: −0.022 ± 0.0029, p < 0.0001) decreased significantly throughout the 3 months treatment period. NSAIDs intake and topical drug application were significantly decreased by 64% (p < 0.0001) and 79% (p < 0.0001) after 12 weeks, respectively. Only 3/239 (1.3%) patients reported side effects probably related to the product. 80.3% were satisfied with the treatment and 75.5% wished to continue treatment. Conclusion This is the first clinical trial showing that C. longa and B. serrata resin can relieve symptoms in patients with hand osteoarthritis. The study provides useful information for the design of a clinical trial including a broader population.

Associations of habitual glucosamine supplementation with incident gout: a large population based cohort study

ObjectivesThe association between habitual glucosamine use and incident gout has not been examined in previous studies. We aimed to evaluate the association of habitual use of glucosamine with the risk of gout in general population.MethodsA total of 436,594 participants (55.4% female) without prior gout at baseline who completed a questionnaire on supplementation use, which included glucosamine, in the UK Biobank were enrolled. Incident gout was recorded from self-report, death register, primary care, and hospital admission data.ResultsAt baseline, 53,433 (22.1%) females and 30,685 (15.8%) males reported habitual glucosamine use. During a median follow-up period of 12.1 years, 1718 (0.7%) females and 5685 (2.9%) males developed gout. After multivariable adjustment for major risk factors, glucosamine use was associated with a significantly lower risk of incident gout in females (hazard ratio [HR], 0.81, 95% confidence interval [CI], 0.71–0.92), but not in males (HR, 1.05, 95% CI, 0.97–1.13), compared with non-use (P-interaction < 0.001). Among females, the inverse association between glucosamine use and gout was stronger in participants with diuretics use (HR, 0.64, 95% CI, 0.50–0.81) than those without diuretics use (HR, 0.89, 95% CI, 0.77–1.03) (P-interaction = 0.015). Moreover, gout genetic risk scores did not significantly modify the association between glucosamine use and the risk of incident gout in males (P-interaction = 0.548) or females (P-interaction = 0.183).ConclusionsHabitual glucosamine use to relieve osteoarthritis pain was related to lower risk of gout in females, but not in males.

Analgesic dorsal root ganglion field stimulation blocks both afferent and efferent spontaneous activity in sensory neurons of rats with monosodium iodoacetate-induced osteoarthritis

Chronic joint pain is common in patients with osteoarthritis (OA). Non-steroidal anti-inflammatory drugs and opioids are used to relieve OA pain, but they are often inadequately effective. Dorsal root ganglion field stimulation (GFS) is a clinically used neuromodulation approach, although it is not commonly employed for patients with OA pain. GFS showed analgesic effectiveness in our previous study using the monosodium iodoacetate (MIA) - induced OA rat pain model. This study was to evaluate the mechanism of GFS analgesia in this model. After osteoarthritis was induced by intra-articular injection of MIA, pain behavioral tests were performed. Effects of GFS on the spontaneous activity (SA) were tested with in vivo single-unit recordings from teased fiber saphenous nerve, sural nerve, and dorsal root. Two weeks after intra-articular MIA injection, rats developed pain-like behaviors. In vivo single unit recordings from bundles teased from the saphenous nerve and third lumbar (L3) dorsal root of MIA-OA rats showed a higher incidence of SA than those from saline-injected control rats. GFS at the L3 level blocked L3 dorsal root SA. MIA-OA reduced the punctate mechanical force threshold for inducing AP firing in bundles teased from the L4 dorsal root, which reversed to normal with GFS. After MIA-OA, there was increased retrograde SA (dorsal root reflex), which can be blocked by GFS. These results indicate that GFS produces analgesia in MIA-OA rats at least in part by producing blockade of afferent inputs, possibly also by blocking efferent activity from the dorsal horn.

Safety and Effectiveness of Platelet Rich Plasma versus Hyaluronic Acid Injection in Pain Management of Hip Osteoarthritis

Background: Platelet rich plasma therapy is a simple, low cost and minimally invasive method that provides a natural concentrate of autologous blood growth factors that can be used to enhance tissue regeneration (1). Recent evidences have shown that Platelet Rich Plasma Therapy can be helpful as an osteoarthritis (OA) therapeutic tool by intra-articular injection (2). Hyaluronic acid (HA) is widely used therapy for relief of OA pain and stiffness by intra-articular injection. In addition, there is a sufficient evidence for being significant disease modifying effects. Objectives: The aim of the study was to compare the clinical efficacy of Platelet Rich Plasma with that of hyaluronic acid viscous supplementation. Methods: This study included forty patients with hip osteoarthritis. These patients were selected from the Out Patient Department (OPD) of Dhaka Pain Management Center (DPMC) and Ava Pain &amp; Intervention Center (APIC), Dhaka, Bangladesh during the period from January 2020 to December 2020. Patients were randomly divided into two groups. The first group consisted of 20 patients treated by using intra-articular injection of 2 ml autologous Platelet Rich Plasma Therapy. The second group consisted of 20 patients they were treated by using intra-articular injections of low molecular weight (hyaluronic acid [HA]) (32mg/2mL) of HA (HA group). All patients received 3 injections with one week interval (3) For Follow up: The subjective clinical outcome were measured at baseline, 1, 3, 6 and 12 months after the last treatment dose using the Visual Analog Scale (VAS) (5). Results: The Platelet rich plasma and Hyaluronic Acid groups showed an improvement, with significant difference between the two groups. However after 6 months follow up there was significant improvement in Platelet Rich Plasma Therapy group than HA group (P&lt;0.005). The follow up after 12 months reveled subsided improvement than that was at 6 months. Nevertheless, this subsidence was less in Platelet ...

Transcatheter arterial embolization of abnormal neovessels in a swine model of knee arthritis

BackgroundIn recent years, transcatheter arterial embolization (TAE) using imipenem/cilastatin (IPM/CS) has attracted attention as a treatment for relieving osteoarthritis (OA) pain. However, IPM/CS is not approved by Japanese medical insurance for use as an embolic material. Therefore, it is necessary to develop new embolic materials for TAE to relieve OA pain. The purpose of this study was to develop a swine model of knee arthritis and embolize abnormal neovessels (ANs) using two different embolic materials. We compared the embolic effects and tissue damage in knees. MethodsKnee arthritis was induced by intra-articular injection of papain into 12 knees in six female swine. The swine were divided into two groups of three swine each (six knees per group) for embolization of ANs in the knees with either IPM/CS or soluble gelatin sponge particles (SGSs). Three days after embolization, we compared the embolic effects using angiography and the tissue damage histopathologically. ResultsANs were observed in all 12 knees at 42 days after papain injection. The ANs disappeared and the patent arteries were recanalized 3 days after TAE in all 12 knees. Histopathological evaluation revealed synovitis changes, such as synovial thickening and inflammatory cell infiltration, in all 12 knees. There was no evidence of skin or muscle necrosis in either group. The appearance of ANs, recanalization of the parent arteries, and histopathological outcomes were not significantly different between the two groups. ConclusionSGSs were as safe as IPM/CS for TAE of ANs in this swine model of knee arthritis.

Management of osteo-arthritic pain by the elderly in Niger

This study aimed to identify how the elderly in Nigeria manage osteo-arthritic pain; their descriptions of osteo-arthritic pain; and the relationship between management strategies and relief of osteo-arthritic pain. Using structured interviews, data were collected from 236 elderly people on the quality of pain experienced; modalities used to manage osteo-arthritic pain; and the effect of such modalities on the pain. The results revealed that most respondents (79.7%) perceived osteo-arthritic pain as being excruciating; occurring all the time (80.9%); and increasing in intensity (68.2%). However, 36.9% asserted that pain was associated with stiffness of swollen joints, while 94.5% indicated that rest relieved the pain. Non-steroidal anti-inflammatory drugs (NSAIDS) were used by most (93.6%) of the respondents; local balm (ori) by 57.3%; various concoctions (abgo) by 14.7%; and traditional powder (agunmu) by 11.9%. Osteo-arthritic pain is a common condition among the elderly in Nigeria. The study found that rest, NSAIDS and local remedies were used to control the pain. Future research should investigate the actions, effectiveness, effective dosages, and potential side-effects of traditional remedies. Health education efforts should inform elderly people about the early signs and symptoms of osteo-arthritis, available remedies and medications as well as the possible side-effects of medications. Elderly women should be warned about the association between being overweight and suffering from osteo-arthritis.

Dopamine-conjugated hyaluronic acid delivered via intra-articular injection provides articular cartilage lubrication and protection

Due to its high molecular weight and viscosity, hyaluronic acid (HA) is widely used for viscosupplementation to provide joint pain relief in osteoarthritis. However, this benefit is temporary due to poor adhesion of HA on articular surfaces. In this study, we therefore conjugated HA with dopamine to form HADN, which made the HA adhesive while retaining its viscosity enhancement capacity. We hypothesized that HADN could enhance cartilage lubrication through adsorption onto the exposed collagen type II network and repair the lamina splendens. HADN was synthesized by carbodiimide chemistry between hyaluronic acid and dopamine. Analysis of Magnetic Resonance (NMR) and Ultraviolet spectrophotometry (Uv–vis) showed that HADN was successfully synthesized. Adsorption of HADN on collagen was demonstrated using Quartz crystal microbalance with dissipation (QCM-D). Ex vivo tribological tests including measurement of coefficient of friction (COF), dynamic creep, in stance (40 N) and swing (4 N) phases of gait cycle indicated adequate protection of cartilage by HADN with higher lubrication compared to HA alone. HADN solution at the cartilage-glass sliding interface not only retains the same viscosity as HA and provides fluid film lubrication, but also ensures better boundary lubrication through adsorption. To confirm the cartilage surface protection of HADN, we visualized cartilage wear using optical coherence tomography (OCT) and atomic force microscopy (AFM).

Sestrin2 overexpression attenuates osteoarthritis pain via induction of AMPK/PGC-1α-mediated mitochondrial biogenesis and suppression of neuroinflammation

BackgroundOur previous study indicated that reactive oxygen species (ROS) are critically involved in chronic pain. Sestrin2 (Sesn2), a novel stress-inducible protein, is evidenced to reduce the generation of ROS. The study examined the role of Sesn2 in osteoarthritis (OA) pain and delineated the underlying molecular mechanisms. MethodsIn the present study, we investigated the impact of Sesn2 on mitochondrial biogenesis in a rat model of OA pain. After adeno-associated viral (AAV)-Sesn2EGFP was injected for 14 days, OA was induced by intra-articular injection of monosodium iodoacetate (MIA). We assessed pain behaviors (weight-bearing asymmetry and paw withdrawal threshold) and explored possible mechanisms in the L4-6 spinal cord. ResultsOur results showed that overexpression of Sesn2 in the spinal cord alleviated pain behaviors in OA rats. Moreover, overexpression of Sesn2 increased the activity of AMP-activated protein kinase (AMPK) signaling and significantly restored mitochondrial biogenesis. Besides, Sesn2 overexpression inhibited the activation of astrocytes and microglia, and decreased the production of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the spinal cord of the OA pain rats. These effects were significantly reversed by an AMPK inhibitor. ConclusionsCollectively, these results suggest that Sesn2 overexpression ameliorates mechanical allodynia and weight-bearing asymmetry in OA rats via activation of AMPK/PGC-1α-mediated mitochondrial biogenesis in the spinal cord. Moreover, Sesn2 overexpression attenuates OA-induced neuroinflammation at least partly by activating AMPK signaling. Sesn2 may become an encouraging therapeutic strategy for OA pain relief and other disorders.

Nutraceuticals for Knee Osteoarthritis Pain Relief. Results from a Preliminary Randomised Clinical Trial

Osteoarthritis is the most common inflammation-based joint disease. Polyphenols are plant secondary metabolites with established antioxidant and anti-inflammatory properties. Recognizing the need for holistic approaches in the management of knee osteoarthritis, we designed a two-arm, randomised clinical trial to evaluate the efficacy of a supplement rich in phenolic compounds in OA. Primary outcomes included changes in Visual Analog Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain subscale. Secondary outcome measures were the changes in WOMAC stiffness and functionality subscales. Patients were randomised (1:1) to receive a mixture of phenolic compounds and ascorbic acid (PhAA,) or ascorbic acid (AA). Μedical history, biochemical profile and anthropometric measurements were obtained. Eighty-six patients were screened and 25 were randomly allocated in a pilot study to receive a mixture of phenolic compounds and ascorbic acid (PhAA,) or ascorbic acid (AA) adjunct to stable medical treatment. The nutraceutical supplements were well tolerated and no adverse events were reported. VAS decreased in the PhAA group (p &lt; 0.001). Additionally, WOMAC composite score decreased significantly only in the PhAA group (p &lt; 0.05). The WOMAC subscale of pain decreased in both treatment groups (p = 0.001 for the PhAA group, p &lt; 0.05 for the AA group). The decrease in the subscales of stiffness and physical function was not significant for either group. A possible improvement in the quality of life of these patients using nutraceutical supplements is apparent. Although preliminary, our positive results support the hypothesis that treatment with nutraceuticals may be effective for pain relief in osteoarthritis. ClinicalTrials.gov Identifier: NCT04783792.

Efficacy of ultramicronised diclofenac in patients with osteoarthritis - systematic review with network meta-analysis.

This systematic review with network meta-analysis was performed to compare the effectiveness of oral anti-inflammatory drugs used in Brazil for osteoarthritis. Randomized clinical trials evaluating ultramicronised diclofenac, diclofenac, celecoxib, etodolac and placebo in patients with osteoarthritis were identified. A search was conducted in May 2021 through PubMed, Scopus and Web of Science databases. A network meta-analysis was developed for efficacy outcome related to analgesia measured by the pain subscale of the Western Ontario and McMaster Universities tool. In addition, surface under the cumulative ranking was performed to rank the drugs in relation to this outcome. Twelve randomized clinical trials were included. Overall, ultramicronised diclofenac 105mg/day (UD105) was better than all the others, including ultramicronised diclofenac 70mg/day (UD70). In addition, surface under the cumulative ranking resulted in the following order: 1) ultramicronised diclofenac 105mg/day (100%), 2) ultramicronised diclofenac 70mg/day (80%), 3) celecoxib 200mg/day (49%), 4) diclofenac 100mg/day (48%), 5) placebo (19%) and 6) diclofenac 150mg/day (6%). Ultramicronised diclofenac demonstrated superior efficacy compared to other conventional anti-inflammatory drugs and placebo in relieving osteoarthritis pain.

Safety and efficacy of single CHAP Hyaluronan injection versus three injections of linear Hyaluronan in pain relief for knee osteoarthritis: a prospective, 52-week follow-up, randomized, evaluator-blinded study

BackgroundThe hyaluronic acid (HA) injections are widely used in knee osteoarthritis (OA) patients. We conducted the study comparing the efficacy and safety of single injection of Crosslinked Hyaluronic Acid Platform Hyaluronan (CHAP-HA) with 3-injection of linear hyaluronan in knee OA patients.MethodsThis was a randomized two-arms, evaluator-blinded, controlled, single-center study. Participants with knee OA received single CHAP-HA or three-injection of linear-HA. The 140 patients aged 35–85 years with radiographically confirmed knee OA were enrolled. At week 4, 12, 26, 39, and 52, visual analog scale (VAS) pain score, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, timed up and go (TUG) and subject’s adverse events (AE) of these 2 groups were recorded. Primary outcome of the differences of VAS pain score at week 26 between groups was analyzed with analysis of covariance (ANCOVA). At week 52, those who met the inclusion criteria could receive a CHAP-HA injection and being followed-up for the adverse events for 4 weeks.ResultsThe trial was conducted from September 2015 to April 2017. A total 140 subjects were available for analysis (71 in the CHAP-HA group and 69 in the linear-HA group). At 26th week, there were significant more improvements in VAS pain scores in CHAP-HA compared with linear-HA. Both CHAP-HA and linear-HA showed significant improvements in the VAS pain score at week 26 compared with the baseline, and the occurrence of adverse events during the study period showed no between-group difference. In subjects with KL = 2, both groups showed significant improvements in VAS pain scores within 26 weeks. In patients with KL = 3, only CHAP-HA group showed significant improvement in VAS pain from 4 to 39 weeks. No unexpected or severe AEs were reported.ConclusionsA single injection of CHAP-HA may be safe and more effective for 26 weeks in patients with knee OA by comparing to linear-HA; moreover, the pain relief effect of CHAP-HA may remain until 52 weeks. For patients with more severe OA, CHAP-HA was demonstrated to be more preferable to relieve OA pain. Furthermore, repeat treatment of CHAP-HA or using CHAP-HA after a three-injection HA was proved to be safe.Trial registrationClinicalTrials.gov: NCT03643588. Date: August 23, 2018 (retrospectively registered).Level of Evidence: Therapeutic Level I.

Effect of Low dose Naltrexone versus Naproxen Extended-release for Pain Relief in knee osteoarthritis, a Triple-blinded, Non-inferiority Phase II Randomized Controlled Trial (FREEDOM) - Study Protocol

Background and objectives: Osteoarthritis (OA) is a degenerative articular disease that affects approximately 240 million people worldwide, with knee OA accounting for 80% of this burden. One of the aims of pharmacological treatment in OA is to reduce pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for pain relief in OA but have considerable renal, hepatic, cardiovascular, and gastrointestinal adverse effects, with the resultant increase in morbidity and mortality. Naltrexone is an orally activated opioid antagonist that has varied dose-dependent pharmacodynamic effects: Analgesic and anti-inflammatory effects are exhibited only at low dosage ranges of 0.5mg to 4.5mg (Low Dose Naltrexone LDN) while retaining a favorable adverse effect profile. This study aims to test the non-inferiority of LDN against Naproxen. Methodology: This is a prospective phase II triple-blinded, two-arm, parallel-group, non-inferiority randomized controlled trial. The intervention group will receive low dose naltrexone 4.5 mg once daily, and the control group will receive extended-release naproxen 1000 mg once daily during the 12 week trial duration. Our sample size will be 118 patients recruited from a single Orthopedic referral center in the USA. Discussion: The use of LDN for pain relief in osteoarthritis (OA) may be beneficial due to its favorable adverse effect profile. To the best of our knowledge, there is no published data on LDN use in OA even though preliminary evidence has documented its safety and tolerability in a variety of chronic pain conditions.

Effect of different types of electrical stimulation on intracellular calcium levels in human mesenchymal stem cells and chondrocytes

Purpose: Electrostimulation (ES) is a noninvasive treatment modality used for pain relief in osteoarthritis (OA). However, the effects of ES are not restricted to peripheral nerves and impact joint tissues also. At the cellular level ES changes the membrane potential and ion fluxes through voltage gated ion channels, thus stimulating intracellular processes and regulating cell differentiation. Voltage gated calcium channels (VGCC) are one of the most important channels enabling calcium ion entry into cells, which further participate in various signaling pathways during cell proliferation, differentiation and metabolism.

Extracellular Vesicles and Their Potential Significance in the Pathogenesis and Treatment of Osteoarthritis.

Osteoarthritis (OA) is a chronic joint disease characterized by inflammation, gradual destruction of articular cartilage, joint pain, and functional limitations that eventually lead to disability. Join tissues, including synovium and articular cartilage, release extracellular vesicles (EVs) that have been proposed to sustain joint homeostasis as well as to contribute to OA pathogenesis. EVs transport biologically active molecules, and OA can be characterized by altered EV counts and composition in synovial fluid. Of EV cargo, specific non-coding RNAs could have future potential as diagnostic biomarkers for early OA. EVs may contribute to the propagation of inflammation and cartilage destruction by transporting and enhancing the production of inflammatory mediators and cartilage-degrading proteinases. In addition to inducing OA-related gene expression patterns in synoviocytes and articular chondrocytes, EVs can induce anti-OA effects, including increased extracellular matrix deposition and cartilage protection. Especially mesenchymal stem cell-derived EVs can alleviate intra-articular inflammation and relieve OA pain. In addition, surgically- or chemically-induced cartilage defects have been repaired with EV therapies in animal models. While human clinical trials are still in the future, the potential of actual cures to OA by EV products is very promising.