OA Pain Research Articles

SPECIALIZED PRO-RESOLVING MEDIATOR MARESIN 1 ATTENUATES PAIN IN A MOUSE MODEL OF OSTEOARTHRITIS

We test whether the specialized pro-resolving molecule Maresin 1 (MaR1) attenuates nociceptive behaviors in mice with osteoarthritis-like pain. OA-like pain behavior was induced by intra-articular injection of monosodium iodoacetate (MIA) and treated with MaR1 (N=6) or vehicle (N=5) by intraperitoneal injection 8 weeks after injury. Mice without MIA injection were used as control (N=6). Nociceptive behaviors were examined by von Frey and dynamic weight bearing measurements. CGRP expression and activated macrophages in the dorsal root ganglion (DRG) were examined by immunofluorescence staining. The inflammatory profile in circulation was assessed by cytokine array. Calcium imaging was performed to assess the in vitro functional response of DRG neurons from animals with OA-like pain behavior to MaR1 with or without RAR Related Orphan Receptor A (RORA) inverse agonist SR3335. MaR1 attenuated knee pain behavior in treated mice (N=6) compared to non-treated mice (N=5) as shown by increased paw withdrawal threshold with a mean difference of 112.2% (95% CI [49.79, 174.6], p=0.0784) at 4 hours and 150.9% (95% CI [104.2, 197.5], p=0.0001) at 4 days post-MaR1 treatment, and increased weight bearing with a mean difference of 20.08% (95% CI [2.798, 37.37], p=0.0277) at 1 day post-MaR1 treatment. CGRP expression and activated macrophages were decreased in the DRG, and inflammatory cytokine levels in the circulation were attenuated. Calcium imaging showed MaR1 reduced the functional response of DRG neurons through RORA. Our results show that MaR1 reduces OA-like pain behavior in mice and could be a potential treatment for OA pain.

Efficacy of denervation for osteoarthritis in the proximal interphalangeal joint (DOP): protocol of a randomized controlled trial

BackgroundOsteoarthritis (OA) contributes increasingly to disability worldwide. There is ample high-quality research on the treatment of knee and hip OA, whereas research on surgical and non-surgical treatment in hand OA is sparse. Limited evidence suggests that education and exercise may improve pain, function, stiffness, and grip strength in hand OA. The established surgical options in hand OA have disadvantages. Prostheses preserve motion but have a high complication rate, whereas fusions decrease function due to limited movement. There is an unmet need for high-quality research on treatment options for hand OA and a need for the development of effective and safe movement-sparing therapies.This study aims to compare the effects of a motion-preserving surgical treatment (denervation of the proximal interphalangeal (PIP) joint) with a patient education and exercise program on patient-reported outcomes and objective function in painful PIP OA.MethodsIn this parallel-group, two-armed, randomized, controlled superiority trial (RCT), 90 participants are assigned to surgical PIP joint denervation or education and exercise. Pain on load 1 year after intervention is the primary outcome measure. Secondary outcome measures include pain at rest, Patient-Rated Wrist and Hand Evaluation (PRWHE), HQ8 score, EQ5D-5L, objective physical function, complications, two-point discrimination, Mini Sollerman, consumption of analgesics, and the need for further surgery. Assessments are performed at baseline, 3 and 6 months, and 1 year after intervention.DiscussionThere are no previous RCTs comparing surgical and non-surgical treatment in PIP OA. If patient education plus exercise or PIP denervation improve function, these treatments could be implemented as first-line treatment options in PIP OA. However, if denervation does not achieve better results than non-surgical treatment, it is not justified to use in PIP OA.Trial registrationProspectively registered in ClinicalTrials.gov (NCT05980793) on 8 August 2023. URL https://classic.clinicaltrials.gov/ct2/show/NCT05980793.

Measuring the effect of the anti-nerve growth factor antibodies bedinvetmab and frunevetmab on quality of life in dogs and cats with osteoarthritis using a validated health-related quality of life outcome measure: an observational real-world study.

Osteoarthritis causes chronic pain, impaired joint function, decreased mobility and negatively impacts quality of life (QOL). Anti-nerve growth factor antibodies bedinvetmab for dogs and frunevetmab for cats are licensed for the alleviation of osteoarthritis pain but their QOL impact is unreported. Our aim was to determine if these therapeutics improve QOL using a validated health-related QOL measure that generates scores in four domains of QOL-energetic and enthusiastic (E/E), happy and content (H/C), active and comfortable (A/C) and calm and relaxed (C/R)-in the dog and three in the cat-vitality, comfort and emotional wellbeing (EWB). Summary scores for physical wellbeing (PWB) and emotional wellbeing (EWB) for dogs and PWB for cats are calculated from the domain scores. Animals received bedinvetmab (dogs) at 0.5-1 mg/kg or frunevetmab (cats) at 1-2.8 mg/kg by subcutaneous injection on days 0, 28 and 56 and owners completed QOL assessments within 48 hours of day 0 and on days 14, 28, 56, 63 and 70 using a study-specific app. Assessments were completed by 75 dog and 56 cat owners. By day 14 there was a statistically significant improvement (p ≤ 0.001) in PWB, EWB and all domains except C/R (p = 0.005) in dogs and in all domains and PWB in the cat. Subsequently there was a continued improvement in all domains and summary scores (p ≤ 0.001) except for H/C in the dog and EWB in the cat, which were excluded from the statistical model. The overall improvement in all domain scores in the cat and E/E and A/C in the dog exceeded the previously reported minimum important difference scores for the QOL measure, indicating a clinically significant change. Treatment with bedinvetmab and frunevetmab produced a significant improvement in the QOL of dogs and cats. This latest evidence for the use of these OA pain medications could be helpful in the clinical management of osteoarthritis and post-marketing clinical trials.

Correlation Between KL Gradings of OA Knee, Kinesiophobia and Pain Among School Teachers: A Cross-Sectional Study

Background: Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. OA is the most common form of arthritis. There are two form of OA, Primary and Secondary OA. Kinesiophobia is a condition in which a patient has an excessive, irritational, and debilitating fear of physical movement and activity resulting from a feeling of vulnerability to painful injury or re injury. The influence of biological (exa-gray changes) as well as severity of pain, Kinesiophobia in individual physical functioning. There are less evidences showing the association of kinesiophobia and pain among school teachers with OA knee. So, this study was designed to find out the association of kinesiophobia and pain among school teachers with OA knee. Methodology: A cross-sectional observational study was conducted. 100 school teachers with unilateral or bilateral OA knee were selected who matched the selection criteria. Both male and female were included. For gradings of OA knee KL grade was taken, for kinesiophobia TAMPA scale was taken, for pain NPRS was taken as an outcome measures. Result: Spearman co-efficient between KL grade and TAMPA scale is 0.835, which indicates there is moderate to high positive correlation between KL grade and TAMPA scale. Spearman co-efficient between NPRS and TAMPA scale is 0.923, which indicates there is high positive (strong positive) correlation between NPRS and TAMPA scale. Spearman co-efficient between NPRS and KL grade is 0.784 which indicates there is moderate positive correlation between NPRS and KL grade. Conclusion: This study concludes that there is positive correlation between gradings of OA knee and kinesiophobia among teachers with OA knee. There is moderate positive correlation between gradings of OA and pain among teachers with OA knee. There is very high positive (Strong positive) correlation between kinesiophobia and pain among teachers with OA knee. Keywords: KL Gradings of OA Knee, OA knee, kinesiophobia, osteoarthritis

Dual effects of dulaglutide on glycemic control and knee osteoarthritis pain in elderly patients with Type 2 diabetes.

Aim: This study aims to evaluate the dual benefits of dulaglutide in improving glycemic control and reducing knee OA pain.Patients & methods: Elderly T2DM patients diagnosed with bilateral knee OA on conventional OA treatment for at least 3 months were studied for their glycemic metrics, OA pain scores and NSAID consumption at baseline, 3 months and 6 months.Results: Significant improvements in glycemic control were observed, HbA1c decreased from 8.7% to 6.5% over 6 months. Pain scores, NSAID, body weight and BMI showed substantial reductions over time. Positive correlation (r=0.73, p<0.001) was found between glycemic control and pain reduction.Conclusion: Dulaglutide improves glycemic control, knee joint OA pain and weight management in elderly patients with T2DM.

Treatment of osteoarthritis by implantation of Mg- and WE43-cylinders - A preclinical study on bone and cartilage changes and their influence on pain sensation in rabbits

With its main features of cartilage degeneration, subchondral bone sclerosis and osteophyte formation, osteoarthritis represents a multifactorial disease with no effective treatment options. As biomechanical shift in the trabecular network may be a driver for further cartilage degeneration, bone enhancement could possibly delay OA progression. Magnesium is known to be osteoconductive and already showed positive effects in OA models. We aimed to use magnesium cylinders to enhance subchondral bone quality, condition of cartilage and pain sensation compared to sole drilling in vivo. After eight weeks of implantation in rabbits, significant increase in subchondral bone volume and trabecular thickness with constant bone mineral density was found indicating favored biomechanics. As representative for pain, a higher number of CD271+ vessels were present in control samples without magnesium. However, this result could not be confirmed by sensitive, objective lameness evaluation using a pressure sensing mat and no positive effect could be shown on either cartilage degeneration evaluated by OARSI score nor the presence of regenerative cells in CD271-stained samples. The presented results show a relevant impact of implanted magnesium on key structures in OA pain with missing clinical relevance regarding pain. Further studies with shifted focus should examine additional structures as joint capsule or osteophytes.

Dietary Inflammatory Index and Magnetic Resonance Imaging-Detected Knee Structural Change and Pain: A 10.7-Year Follow-up Study.

To determine whether the dietary inflammatory index (DII) scores were associated with knee structural changes and pain over a 10.7-year follow-up. This study used data from a prospective population-based cohort study (mean age 63 years, 51% female) in which 1,099, 875, 768, and 566 participants completed assessments at baseline, 2.6, 5.1, and 10.7 years, respectively. T1-weighted and T2-weighted magnetic resonance imaging was performed to measure cartilage volume (CV) and bone marrow lesions (BMLs) at baseline and 10.7 years. The Western Ontario and McMaster Universities Osteoarthritis Index pain questionnaire was used to measure knee pain at each visit. Pain trajectories ("minimal pain," "mild pain," and "moderate pain") were previously identified. Baseline energy-adjusted DII (E-DII) scores were calculated. Linear, log-binomial regression, linear mixed-effects modeling, and multi-nominal logistic regression were used for analyses. The mean ± SD E-DII score at baseline was -0.48 ± 1.39. In multivariable analyses, higher E-DII scores were not associated with tibial CV loss or BML size increase except for medial tibial BML size increase. Higher E-DII scores were associated with a higher pain score (β=0.21; 95% confidence interval [CI] 0.004-0.43) and an increased risk of belonging to the "moderate pain" compared to the "minimal pain" trajectory group (relative risk ratio 1.19; 95% CI 1.02-1.39). A proinflammatory diet, as indicated by a higher DII score, may be associated with a greater pain score and higher risk of more severe pain trajectory over 10 years. However, inconsistent findings related to structural changes suggest a discordance between the potential impact of diet on structural damage and pain in knee OA.

Targeting an inflammation-amplifying cell population can attenuate osteoarthritis-associated pain

BackgroundUnderstanding of pain in osteoarthritis, its genesis, and perception is still in its early stages. Identification of precise ligand-receptor pairs that transduce pain and the cells and tissues in which they reside will elucidate new therapeutic approaches for pain management. Our recent studies had identified an inflammation-amplifying (Inf-A) cell population that is expanded in human OA cartilage and is distinctive in the expression of both IL1R1 and TNF-R2 receptors and active Jnk signaling cascade.MethodsIn this study, we have tested the function of the cartilage-resident IL1R1+TNF-R2+ Inf-A cells in OA. We have identified that the IL1R1+TNF-R2+ Inf-A cells expand in aged mice as well as after anterior cruciate ligament tear upon tibia loading and OA initiation in mice. We targeted and modulated the Jnk signaling cascade in InfA through competitive inhibition of Jnk signaling in mice and human OA explants and tested the effects on joint structure and gait in mice.ResultsModulation of Jnk signaling led to attenuation of inflammatory cytokines CCL2 and CCL7 without showing any structural improvements in the joint architecture. Interestingly, Jnk inhibition and lowered CCL2 and 7 are sufficient to significantly improve the gait parameters in treated PTOA mice demonstrating reduced OA-associated pain. Consistent with the mice data, treatment with JNK inhibitor did not improve human OA cartilage explants.ConclusionThese studies demonstrate that Inf-A, an articular-cartilage resident cell population, contributes to pain in OA via secretion of CCL2 and 7 and can be targeted via inhibition of Jnk signaling.

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.

Investigating mechanical and inflammatory pathological mechanisms in osteoarthritis using MSC-derived osteocyte-like cells in 3D.

Changes to bone physiology play a central role in the development of osteoarthritis with the mechanosensing osteocyte releasing factors that drive disease progression. This study developed a humanised in vitro model to detect osteocyte responses to either interleukin-6, a driver of degeneration and bone remodelling in animal and human joint injury, or mechanical loading, to mimic osteoarthritis stimuli in joints. Human MSC cells (Y201) were differentiated in 3-dimensional type I collagen gels in osteogenic media and osteocyte phenotype assessed by RTqPCR and immunostaining. Gels were subjected to a single pathophysiological load or stimulated with interleukin-6 with unloaded or unstimulated cells as controls. RNA was extracted 1-hour post-load and assessed by RNAseq. Markers of pain, bone remodelling, and inflammation were quantified by RT-qPCR and ELISA. Y201 cells embedded within 3D collagen gels assumed dendritic morphology and expressed mature osteocytes markers. Mechanical loading of the osteocyte model regulated 7564 genes (Padj p<0.05, 3026 down, 4538 up). 93% of the osteocyte transcriptome signature was expressed in the model with 38% of these genes mechanically regulated. Mechanically loaded osteocytes regulated 26% of gene ontology pathways linked to OA pain, 40% reflecting bone remodelling and 27% representing inflammation. Load regulated genes associated with osteopetrosis, osteoporosis and osteoarthritis. 42% of effector genes in a genome-wide association study meta-analysis were mechanically regulated by osteocytes with 10 genes representing potential druggable targets. Interleukin-6 stimulation of osteocytes at concentrations reported in human synovial fluids from patients with OA or following knee injury, regulated similar readouts to mechanical loading including markers of pain, bone remodelling, and inflammation. We have developed a reproducible model of human osteocyte like cells that express >90% of the genes in the osteocyte transcriptome signature. Mechanical loading and inflammatory stimulation regulated genes and proteins implicated in osteoarthritis symptoms of pain as well as inflammation and degeneration underlying disease progression. Nearly half of the genes classified as 'effectors' in GWAS were mechanically regulated in this model. This model will be useful in identifying new mechanisms underlying bone and joint pathologies and testing drugs targeting those mechanisms.

Relationship between the Serum Cartilage Oligomeric Matrix Protein Concentration against Degree of Knee Osteoarthritis Pain in Elderly Patients at the Public Health Service Clinic

This study aims to assess the relationship between the serum concentration of Cartilage Oligomeric Matrix Protein (COMP) and the degree of osteoarthritis pain in elderly patients. The study was conducted at a public health service clinic, Faculty of Medicine, Syarif Hidayatullah State Islamic University (UIN) Jakarta, Indonesia. The indexes used to assess patients with OA in the knee are the Western Ontario and Mcmaster University Osteoarthritis Index (WOMAC). Sampling using the cross-sectional technique as many as 146 respondents with elderly knee OA patients. First, a physical and radiological examination is performed to confirm the diagnosis of knee OA. Second, measuring the degree of pain WOMAC. Third, the measurement of the COMP serum concentration used the ELISA test. Based on the Spearman correlation test, it was found that there was a statistically significant relationship between the COMP serum concentration and the degree of knee OA pain with the WOMAC scale in the elderly (p = 0.012). From the results of the study, it is suggested that patients maintain effective health management. Elderly patients come to community health service clinics to carry out routine/periodic checks to reduce pain. The main reason is that there is no truly effective and consistent method to prevent and cure this disease, especially for patients with age-related risk factors, excessive joint load, and a history of joint injury. AO also has an impact on a person's psychosocial well-being. These findings contribute to the study of the risk of degenerative diseases and the use of biomarkers with a level of evidence that will be more valid in the future.

Associations of Muscle Strength with Central Aspects of Pain: Data from the Knee Pain and Related Health in the Community (KPIC) Cohort.

Knee pain is associated with lower muscle strength, and both contribute to disability. Peripheral and central neurological mechanisms contribute to OA pain. Understanding the relative contributions of pain mechanisms to muscle strength might help future treatments. The Knee Pain and related health In the Community (KPIC) cohort provided baseline and year 1 data from people with early knee pain (n = 219) for longitudinal analyses. A cross-sectional analysis was performed with baseline data from people with established knee pain (n = 103) and comparative data from people without knee pain (n = 98). Quadriceps and handgrip strength indicated local and general muscle weakness, respectively. The indices of peripheral nociceptive drive were knee radiographic and ultrasound scores. The indices associated with central pain mechanisms were Pressure Pain detection Threshold (PPT) distal to the knee, and a validated self-report Central Aspects of Pain Factor (CAPF). The associations were explored using correlation and multivariable regression. Weaker quadriceps strength was associated with both high CAPF and low PPT at baseline. Year 1 quadriceps weakness was predicted by higher baseline CAPF (β = -0.28 (95% CI: -0.55, -0.01), p = 0.040). Weaker baseline and year 1 handgrip strength was also associated with higher baseline CAPF. Weaker baseline quadriceps strength was associated with radiographic scores in bivariate but not adjusted analyses. Quadriceps strength was not significantly associated with total ultrasound scores. Central pain mechanisms might contribute to muscle weakness, both locally and remote from the knee.

Artemin sensitizes nociceptors that innervate the osteoarthritic joint to produce pain

There have been significant developments in understanding artemin/GFRα3 signaling in recent years, and there is now accumulating evidence that artemin has important roles to play in pain signaling, including that derived from joint and bone, and that associated with OA. A total of 163 Sprague Dawley rats were used in this study. We used an animal model of mono-iodoacetate (MIA)-induced OA, in combination with electrophysiology, behavioral testing, Western blot analysis, and retrograde tracing and immunohistochemistry, to identify roles for artemin/GFRα3 signaling in the pathogenesis of OA pain. We have found that: 1) GFRα3 is expressed in a substantial proportion of knee joint afferent neurons; 2) exogenous artemin sensitizes knee joint afferent neurons in naïve rats; 3) artemin is expressed in articular tissues of the joint, but not surrounding bone, early in MIA-induced OA; 4) artemin expression increases in bone later in MIA-induced OA when pathology involves subchondral bone; and 5) sequestration of artemin reverses MIA-induced sensitization of both knee joint and bone afferent neurons late in disease when there is inflammation of knee joint tissues and damage to the subchondral bone. Our findings show that artemin/GFRα3 signaling has a role to play in the pathogenesis of OA pain, through effects on both knee joint and bone afferent neurons, and suggest that targeted manipulation of artemin/GFRα3 signaling may provide therapeutic benefit for the management of OA pain.

Notch signalling mediates OA pain in mice.

Notch signalling mediates OA pain in mice.

Full spectrum medical cannabis (Vijaya) oil as a veterinary treatment for osteoarthritis, hip dysplasia and musculoskeletal disorders: A case series

In veterinary medicine, Osteoarthritis, Hip Dysplasia and pain disorders are commonly diagnosed conditions, and it presents significant difficulties for the well-being of canines. The aim of this case series is to report the use of full spectrum medical cannabis (vijaya) for treating symptoms such as pain, inflammation, impaired mobility. Four Labrador breed patients between 6 years to 8 years, suffering from acute mobility issues were diagnosed with OA and HD. All patients were administered 4 drops of the full spectrum oil, orally, twice daily. After one month of the treatment, there was significant change in the pain markers with improved mobility. The recommended dose is 0.16 mg/kg/body wt for management of OA and HD related pain and inflammation. A boost in appetite and quality of life was also observed. In the future it is important to incorporate new treatment options in the medical practice and further research needs to be conducted on its use for other illnesses and animal species.

Effects of a Massive Open Online Course on osteoarthritis knowledge and pain self-efficacy in people with hip and/or knee osteoarthritis: protocol for the MOOC-OA randomised controlled trial

BackgroundOsteoarthritis (OA) is a prevalent, chronic joint condition that commonly affects the knee and hip causing pain, impaired function, and reduced quality of life. As there is no cure, the main goal of treatment is to alleviate symptoms via ongoing self-management predominantly consisting of exercise and weight loss (if indicated). However, many people with OA do not feel adequately informed about their condition and management options to self-manage effectively. Patient education is recommended by all OA Clinical Practice Guidelines to support appropriate self-management, but little is known about the optimal delivery method and content. Massive Open Online Courses (MOOCs) are free, interactive, e-learning courses. They have been used to deliver patient education in other chronic health conditions but have not been used in OA.MethodsA two-arm parallel-design, assessor- and participant-blinded superiority randomised controlled trial. People with persistent knee/hip pain consistent with a clinical diagnosis of knee/hip OA (n = 120) are being recruited from the Australia-wide community. Participants are randomly allocated into one of two groups i) electronic information pamphlet (control group) or ii) MOOC (experimental group). Those allocated to the control group receive access to an electronic pamphlet about OA and its recommended management, currently available from a reputable consumer organisation. Those allocated to the MOOC receive access to a 4-week 4-module interactive consumer-facing e-Learning course about OA and its recommended management. Course design was informed by behaviour theory and learning science, and consumer preferences. The two primary outcomes are OA knowledge and pain self-efficacy with a primary endpoint of 5 weeks and a secondary endpoint of 13 weeks. Secondary outcomes include measures of fear of movement, exercise self-efficacy, illness perceptions, OA management and health professional care seeking intentions, physical activity levels, and actual use of physical activity/exercise and weight loss, pain medication, and health professional care seeking to manage joint symptoms. Clinical outcomes and process measures are also collected.DiscussionFindings will determine whether a comprehensive consumer-facing MOOC improves OA knowledge and confidence to self-manage joint pain compared to a currently available electronic OA information pamphlet.Trial registrationProspectively registered (Australian New Zealand Clinical Trials Registry ID: ACTRN12622001490763).

Vitamin D reduces pain and cartilage destruction in knee osteoarthritis animals through inhibiting the matrix metalloprotease (MMPs) expression

Aim of the studyIn this study, we investigated the therapeutic potential of vitamin D (VITD) in OA Wistar rats induced by anterior cruciate ligament transection combined with medial meniscectomy (ACLT + MMx). In ACLT + MMx-induced OA rats, pain severity, cartilage destruction, inflammatory cytokines, and MMPs were all measured. Materials and methodsACLT + MMx methods were used to induce OA, and pain behavioral studies such as the weight bearing test and paw withdrawal test were performed while the knee width and body weights were also measured. Furthermore, Hematoxylin and Eosin (H&E) staining was used to determine knee histopathological studies, as well as OARSI scoring, cartilage thickness, cartilage width, and cartilage degradation scores. The enzyme-linked immunosorbent assay (ELISA) studies were used to check the serum levels of VITD, C-telopeptide of Type II collagen (CTX-II), and pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and anti-inflammatory cytokines interleukin-10 (IL-10), and MMPs (MMP-3, MMP-9, and MMP-13). Finally, the reverse transcription polymerase chain reaction (RT-PCR) test was used to determine the levels of MMPs, nuclear factor-kappa B (NF-κB), TNF-α, IL-6, and IL-10 in IL-1β stimulated chondrocytes. ResultsThe oral VITD supplement significantly reduced OA pain, inflammation, cartilage destruction, and MMPs levels. Furthermore, serum VITD levels increased while CTX-II levels decreased, indicating that VITD reduced cartilage degradation effectively. Moreover, VITD supplementation reduced the expression of pro-inflammatory TNF-α, IL-1β, and IL-6 cytokines while increasing the expression of anti-inflammatory IL-10. The elevation of MMPs after ACLT + MMx surgery contributed to articular cartilage destruction, which was reduced by VITD supplementation. Finally, VITD supplementation significantly reduces serum levels of MMPs, IL-1β, TNF-α, and IL-6 while increasing IL-10 levels. Then, using the in-vitro cytotoxicity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) MTT assay, examine the cytotoxicity profile of VITD in rat chondrocytes after stimulated with IL-1β, which shows no toxicity in the dose range of VITD 0–500 IU. Finally, RT-PCR studies in IL-1β stimulated rat chondrocytes revealed that VITD (50, 100, and 500 IU) significantly reduced the mRNA levels of MMPs, NF-κB, TNF-α, and IL-6, while increasing IL-10 levels, indicating that VITD reduced chondrocyte destruction and overcame harsh conditions in a dose-dependent manner. ConclusionOverall, the in vivo and in vitro findings show that VITD effectively reduces OA pain, inflammation, and chondrocyte destruction by lowering MMPs levels specifically.

Palmitoyl-glucosamine co-micronized with curcumin for maintenance of meloxicam-induced pain relief in dogs with osteoarthritis pain

BackgroundOsteoarthritis (OA) pain is the number one cause of chronic pain in dogs. Multimodal treatment, including combining safe and effective nutritional interventions with non-steroidal anti-inflammatory drugs (NSAIDs), is currently considered one of the most appropriate choices for managing OA pain. Palmitoyl-glucosamine is a feed material belonging to the ALIAmide family, whose parent molecule is the prohomeostatic lipid amide N-palmitoyl-ethanolamine. Curcumin is a promising plant antioxidant. The present study aimed at investigating whether 18-week dietary integration with palmitoyl-glucosamine co-micronized with curcumin was able to maintain pain relief in dogs with OA-associated chronic pain receiving meloxicam (1.5 mg/ml oral suspension) on a tapering regimen (progressive 25% decrease of the original 0.1 mg/kg/day dose, on a biweekly basis) during the first 8 weeks of treatment. Pain was assessed both by the owners and veterinary surgeons, with the first using both subjective evaluation and validated metrology instruments—i.e., Helsinki Chronic Pain Index (HCPI) and Canine Brief Pain Inventory (CBPI)—while the second rating the severity of lameness and pain on palpation on two previously used 5-point scales.ResultsA total of fifty-eight dogs with OA chronic pain entered the uncontrolled study. Pain on HCPI was considered severe at baseline (range 18–39). Based on owner’s assessment, 90% of dogs who responded to meloxicam at the full-dose regimen could reduce meloxicam up to 25% of the original dose without experiencing pain worsening. Moreover, 75% of dogs was assessed as having no pain increase ten weeks after meloxicam withdrawal. A statistically significant decrease of pain severity as scored by HCPI (P < 0.0001) was observed two and ten weeks after meloxicam withdrawal compared to study entry (17.0 ± 1.05 and 15.1 ± 1.02, respectively, vs 29.0 ± 0.74; mean ± SEM). After meloxicam withdrawal, no statistically significant change in the CBPI scores was recorded. Pain on palpation and lameness significantly changed to less severe distributions along the study period (P < 0.0001).ConclusionThe findings appear to suggest that dietary integration with palmitoyl-glucosamine co-micronized with curcumin was able to maintain meloxicam-induced pain relief in dogs with severe OA chronic pain.

Study of the effectiveness of glucosamine and chondroitin sulfate, marine based fatty acid compounds (PCSO-524 and EAB-277), and carprofen for the treatment of dogs with hip osteoarthritis: A prospective, block-randomized, double-blinded, placebo-controlled clinical trial.

Glucosamine hydrochloride and chondroitin sulfate are commonly used in dogs with OA, but evidence around efficacy is mixed. This study evaluated the effectiveness of glucosamine and chondroitin sulfate, marine based fatty acid compounds (PCSO-524 and EAB-277), and carprofen for the alleviation of canine hip OA pain. This was a prospective, block-randomized, double-blinded, placebo-controlled clinical trial. Seventy-five owned pet dogs with hip OA were assigned randomly into five treatment groups: PCSO-524, Glucosamine and chondroitin sulfate, EAB-277, carprofen, and Placebo (sunflower oil). Peak vertical force (PVF) and subjective orthopedic assessment scores (OAS) were evaluated before treatment (week 0), and at weeks 2, 4, and 6 during treatment. At week 2, the carprofen group showed a significant increase in PVF (3.14 ± 5.33; mean ± SD). After 4 weeks, the increases in PVF of the PCSO-524 (3.90 ± 3.52), EAB-277 (4.17 ± 4.94), and carprofen (3.08 ± 5.87) groups were significant, and significantly greater than placebo (0.08 ± 1.90) and glucosamine (-0.05 ± 6.34) groups. After 6 weeks, the change of PVF in the PCSO-524 (4.14 ± 4.65), EAB-277 (4.45 ± 4.23), and carprofen (4.21 ± 6.52) groups were significant and significantly higher than the placebo group (-0.33 ± 3.65). The change in PVF in the glucosamine group (1.08 ± 5.49) lay between the placebo group and the other treatment groups. The OAS did not show any significant change in any group. PCSO-524 and EAB-277, but not glucosamine/chondroitin, resulted in significant improvements in PVF from baseline after 4 weeks, and 6 weeks, and to a similar degree to that seen with carprofen.

Comment on: Whole grain consumption and risk of radiographic knee osteoarthritis: a prospective study from the Osteoarthritis Initiative.

Dear Editor, We read the recent publication by Liu et al. with great interest [1]. They provided a possible dietary intervention for the prevention of radiographic OA of the knee for people at risk for OA. The researchers showed an inverse association between the risk of developing radiographic knee OA and whole grain consumption in their prospective cohort study. Evidence contributing to the prevention of OA has great value, because it is difficult to manage symptoms related to clinical OA, especially since the prevalence of OA is increasing and more and more people struggle with OA due to increasing obesity and prolonged life expectancy [2]. Even though we appreciate the work of Liu et al. in the prevention of OA, two main questions regarding their methods remain. First, we wonder whether the researchers also considered looking into the development of clinical OA or knee pain in their participants. The results published in the study only focus on the development of radiographic OA. In our opinion, increasing the scope of the study and also looking at clinical symptoms of OA would be a valuable addition, because the presence of radiographic OA is a poor predictor of knee pain in patients [3]. The burden of OA comes from the symptoms a patient experiences, such as pain, stiffness or functional loss. Investigating whether whole grain consumption has an association with the development of OA symptoms would make the results of the study more applicable for clinical practice.