Krill oil supplementation for knee pain: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

INTRODUCTION: Knee pain is a major cause of disability worldwide, particularly among the elderly. Current treatments, including nonsteroidal anti-inflammatory drugs and analgesics, often lead to adverse effects. Krill oil is being explored as a potential alternative, however its efficacy in managing knee symptoms remains unclear. METHODS: MEDLINE, Embase, and Cochrane databases were searched until May 2024 for studies comparing krill oil and placebo in knee pain patients. Endpoints included knee pain, stiffness, physical function, and lipid profiles (HDL-C, LDL-C, triglycerides, and total cholesterol). A restricted maximum likelihood random-effects model with standardized mean differences (SMD) and 95% confidence intervals (CI) was used. A trial sequential analysis was conducted to evaluate further research implications. RESULTS: We included five trials with 700 patients using krill oil for knee pain. Results showed no significant difference between krill oil and placebo for knee pain, knee stiffness, and lipid profiles. However, krill oil demonstrated a significant small effect in improving knee physical function (SMD -0.24, 95% CI [-0.41; -0.08], I2 = 0%).Trial sequential analysis provided certainty that krill oil enhances knee physical function compared to placebo and indicated no improvement in knee pain, but the findings for knee stiffness need to be confirmed by further research. CONCLUSION: This study found that krill oil supplementation did not significantly improve knee pain, stiffness, or lipid profile, although it may help knee physical function. Based on these findings, krill oil supplementation is not yet justified for knee pain.

From maca to marijuana: cultural influences on joint pain symptoms and management in urban perimenopausal and early postmenopausal Latinas.

OBJECTIVE: The purpose of this qualitative study was to explore the symptom experience and coping strategies for managing joint pain during the menopause transition in urban Latina women. METHODS: We conducted focus groups with 13 English-speaking peri and early postmenopausal Latinas living in Upper Manhattan in New York City in 2014. Eligible participants were self-identified Latinas aged 45 to 60 years with new onset or worsening joint pain and spontaneous amenorrhea, recruited through flyers and snowball sampling. Focus group interviews conducted in English were audiotaped, transcribed, and analyzed by a bilingual research team, using NVivo software (QSR International) to organize and code themes. RESULTS: On average, participants were aged 51.7 ± 4.8 years and overweight (body mass index of 29.3 ± 6.7 kg/m 2 ); 10 (76.9%) were Puerto Rican, and the last menstrual period was 1 month to 5 years ago. The following four themes emerged: 1) menopause and joint pain are an alarming package; 2) pain disrupts life and livelihood; 3) medical management is unsatisfactory and raises worries about addiction; and 4) home remedies for coping with pain-from maca to marijuana. Despite access to a world-class medical facility in their neighborhood, women seeking pain relief preferred to self-manage joint pain with exercise, over-the-counter products, and other culturally valued home remedies. Many suffered through it. CONCLUSIONS: For midlife Latinas, joint pain symptoms may emerge or worsen unexpectedly as part of the menopause transition and carry distressing consequences for daily activities and quality of life. There is a need to develop more culturally specific approaches for menopause-related pain management in this underserved population.

Pain Reduction With Oral Methotrexate in Knee Osteoarthritis : A Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: Treatments for osteoarthritis (OA) are limited. Previous small studies suggest that the antirheumatic drug methotrexate may be a potential treatment for OA pain. OBJECTIVE: To assess symptomatic benefits of methotrexate in knee OA (KOA). DESIGN: A multicenter, randomized, double-blind, placebo-controlled trial done between 13 June 2014 and 13 October 2017. (ISRCTN77854383; EudraCT: 2013-001689-41). SETTING: 15 secondary care musculoskeletal clinics in the United Kingdom. PARTICIPANTS: A total of 207 participants with symptomatic, radiographic KOA and knee pain (severity ≥4 out of 10) on most days in the past 3 months with inadequate response to current medication were approached for inclusion. INTERVENTION: Participants were randomly assigned 1:1 to oral methotrexate once weekly (6-week escalation 10 to 25 mg) or matched placebo over 12 months and continued usual analgesia. MEASUREMENTS: The primary end point was average knee pain (numerical rating scale [NRS] 0 to 10) at 6 months, with 12-month follow-up to assess longer-term response. Secondary end points included knee stiffness and function outcomes and adverse events (AEs). RESULTS: A total of 155 participants (64% women; mean age, 60.9 years; 50% Kellgren-Lawrence grade 3 to 4) were randomly assigned to methotrexate (n = 77) or placebo (n = 78). Follow-up was 86% (n = 134; methotrexate: 66, placebo: 68) at 6 months. Mean knee pain decreased from 6.4 (SD, 1.80) at baseline to 5.1 (SD, 2.32) at 6 months in the methotrexate group and from 6.8 (SD, 1.62) to 6.2 (SD, 2.30) in the placebo group. The primary intention-to-treat analysis showed a statistically significant pain reduction of 0.79 NRS points in favor of methotrexate (95% CI, 0.08 to 1.51; P = 0.030). There were also statistically significant treatment group differences in favor of methotrexate at 6 months for Western Ontario and McMaster Universities Osteoarthritis Index stiffness (0.60 points [CI, 0.01 to 1.18]; P = 0.045) and function (5.01 points [CI, 1.29 to 8.74]; P = 0.008). Treatment adherence analysis supported a dose-response effect. Four unrelated serious AEs were reported (methotrexate: 2, placebo: 2). LIMITATION: Not permitting oral methotrexate to be changed to subcutaneous delivery for intolerance. CONCLUSION: Oral methotrexate added to usual medications demonstrated statistically significant reduction in KOA pain, stiffness, and function at 6 months. PRIMARY FUNDING SOURCE: Versus Arthritis.

Well-defined alginate oligosaccharides ameliorate joint pain and inflammation in a mouse model of gouty arthritis.

Background: Gouty arthritis causes severe pain and inflammation. Alginate oligosaccharides (AOSs) are natural products derived from alginate and have anti-inflammatory properties. We explored the potential effects of AOSs with different degrees of polymerization (Dp) on gouty arthritis and associated mechanisms. Methods: We established a mouse model of gouty arthritis by injecting monosodium urate (MSU) into ankle joint. Nocifensive behavior, gait and ankle swelling were used to study AOS's effects. Biochemical assays, in vivo imaging, live cell Ca2+ imaging, electrophysiology, RNA-sequencing, etc. were used for mechanism exploration. Results: AOS2 (Dp=2), AOS3 (Dp=3) and AOS4 (Dp=4) all inhibited ankle swelling, whereas AOS2&3 produced the most obvious analgesia on model mice. AOS3, which was picked for further evaluation, produced dose-dependent ameliorative effects on model mice. AOS3 reversed gait impairments but did not alter locomotor activity. AOS3 inhibited NLRP3 inflammasome activation and inflammatory cytokine up-regulation in ankle joint. AOS3 ameliorated MSU-induced oxidative stress and reactive oxygen species (ROS) production both in vivo and in vitro and reversed the impaired mitochondrial bioenergetics. AOS3 activated the Nrf2 pathway and promoted Nrf2 disassociation from Keap1-bound complex and Nrf2 nuclear translocation, thus facilitating antioxidant gene expression via Nrf2-dependent mechanism. Nrf2 gene deficiency abolished AOS3's ameliorative effects on pain, inflammation and oxidative stress in ankle joints of model mice. AOS3 reduced TRPV1 functional enhancement in DRG neurons and constrained neuroactive peptide release. Conclusions: AOS3 ameliorates gouty arthritis via activating Nrf2-dependent antioxidant signaling, resulting in suppression of ROS-mediated NLRP3 inflammasome activation and TRPV1 enhancement. AOS3 may be novel therapeutics for gouty arthritis.

Tuina on knee pain and functional decline of lower limbs for patients with mild-to-moderate knee osteoarthritis in Shanghai: protocol for a multicentre, assessor-blinded, randomised controlled trial.

INTRODUCTION: Knee osteoarthritis (KOA) is one of the most common osteoarthritis, imposing substantial economic and medical burdens on both individuals and society. In China, Tuina has been selected as a complementary and alternative therapy to relieve knee pain and dysfunction symptoms. However, the current evidence is insufficient to support the efficacy of Tuina therapy in addressing knee pain and improving physical function. The trial aims to compare the effectiveness of Tuina with celecoxib, which is considered as the standard treatment, and to assess its potential as an alternative therapy through changes in outcome measures. METHODS AND ANALYSIS: A total of 360 KOA patients aged between 40 and 70 years and classified as Kellgren and Lawrence grades I-II will be recruited from eight subcentral hospitals. The participants will be randomly assigned to either the treatment group (Tuina, Biw) or the control group (celecoxib, Qd), with both groups undergoing a 4-week intervention phase followed by an 8-week follow-up phase. The primary outcome is the change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale at week 4 compared with baseline. Secondary outcomes including WOMAC stiffness and function subscales, WOMAC total score, 36-item Short-Form Health Survey, Timed Up and Go test, Short Physical Performance Battery, gait analysis parameters and pain medication records will be assessed at weeks 4, 8 and 12. Any adverse events that occur during the trial will be promptly recorded. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine (2023SHL-KY-16-01, 2023SHL-KY-16-02). Written informed consent will be obtained from all participants. Study results will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2300069416.

Time-Dependent Effect of Eggshell Membrane on Monosodium-Iodoacetate-Induced Osteoarthritis: Early-Stage Inflammation Control and Late-Stage Cartilage Protection.

Osteoarthritis (OA) is a chronic degenerative joint disease that causes chronic pain, swelling, stiffness, disability, and significantly reduces the quality of life. Typically, OA is treated using painkillers and non-steroidal anti-inflammatory drugs (NSAIDs). While current pharmacologic treatments are common, their potential side effects have prompted exploration into functional dietary supplements. Recently, eggshell membrane (ESM) has emerged as a potential functional ingredient for joint and connective tissue disorders due to its clinical efficacy in relieving joint pain and stiffness. Despite promising clinical evidence, the effects of ESM on OA progression and its mechanism of action remain poorly understood. This study evaluated the efficacy of Ovomet®, a powdered natural ESM, against joint pain and disease progression in a monosodium iodoacetate (MIA)-induced rodent model of OA in mice and rats. The results demonstrate that ESM significantly alleviates joint pain and attenuates articular cartilage destruction in both mice and rats that received oral supplementation for 5 days prior to OA induction and for 28 days thereafter. Interestingly, ESM significantly inhibited mRNA expression levels of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), as well as inflammatory mediators, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase in the knee joint cartilage at the early stage of OA, within 7 days after OA induction. However, this effect was not observed in the late stage at 28 days after OA induction. ESM further attenuates the induction of protein expression for cartilage-degrading enzymes like matrix metalloproteinase (MMPs) 3 and 13, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), in the late-stage. In addition, MIA-induced reduction of the protein expression levels of cartilage components, cartilage oligomeric matrix protein (COMP), aggrecan (ACAN) and collagen type II α-1 chain (COL2α1), and cartilage extracellular matrix (ECM) synthesis promoting transcriptional factor SRY-Box 9 (SOX-9) were increased via ESM treatment in the cartilage tissue. Our findings suggest that Ovomet®, a natural ESM powder, is a promising dietary functional ingredient that can alleviate pain, inflammatory response, and cartilage degradation associated with the progression of OA.

Current challenges in the discovery of treatments against Mayaro fever.

INTRODUCTION: Mayaro fever is an emerging viral disease that manifests as an acute febrile illness. The disease is self-limiting, however joint pain can persist for months leading to chronic arthralgia. There is no specific treatment available, which ultimately leads to socioeconomic losses in populations at risk as well as strains to the public health systems. AREAS COVERED: We reviewed the candidate treatments proposed for Mayaro virus (MAYV) infection and disease, including antiviral compounds targeting viral or host mechanisms, and pathways involved in disease development and pathogenicity. We assessed compound screening technologies and experimental infection models used in these studies and indicated the advantages and limitations of available technologies and intended therapeutic strategies. EXPERT OPINION: Although several compounds have been suggested as candidate treatments against MAYV infection, notably those with antiviral activity, most compounds were assessed only in vitro. Compounds rarely progress toin vivo or preclinical studies, and such difficulty may be associated with limited experimental models. MAYV biology is largely inferred from related alphaviruses and reflected by few studies focusing on target proteins or mechanisms of action for MAYV. Therapeutic strategies targeting pathogenic inflammatory responses have shown potential against MAYV-induced disease in vivo, which might reduce long-term sequelae.

Krill Oil for Knee Osteoarthritis: A Randomized Clinical Trial.

Importance: Knee osteoarthritis is disabling, with few effective treatments. Preliminary evidence suggested that krill oil supplementation improved knee pain, but effects on knee osteoarthritis remain unclear. Objective: To evaluate efficacy of krill oil supplementation, compared with placebo, on knee pain in people with knee osteoarthritis who have significant knee pain and effusion-synovitis. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled clinical trial in 5 Australian cities. Participants with clinical knee osteoarthritis, significant knee pain, and effusion-synovitis on magnetic resonance imaging were enrolled from December 2016 to June 2019; final follow-up occurred on February 7, 2020. Interventions: Participants were randomized to 2 g/d of krill oil (n = 130) or matching placebo (n = 132) for 24 weeks. Main Outcomes and Measures: The primary outcome was change in knee pain as assessed by visual analog scale (range, 0-100; 0 indicating least pain; minimum clinically important improvement = 15) over 24 weeks. Results: Of 262 participants randomized (mean age, 61.6 [SD, 9.6] years; 53% women), 222 (85%) completed the trial. Krill oil did not improve knee pain compared with placebo (mean change in VAS score, -19.9 [krill oil] vs -20.2 [placebo]; between-group mean difference, -0.3; 95% CI, -6.9 to 6.4) over 24 weeks. One or more adverse events was reported by 51% in the krill oil group (67/130) and by 54% in the placebo group (71/132). The most common adverse events were musculoskeletal and connective tissue disorders, which occurred 32 times in the krill oil group and 42 times in the placebo group, including knee pain (n = 10 with krill oil; n = 9 with placebo), lower extremity pain (n = 1 with krill oil; n = 5 with placebo), and hip pain (n = 3 with krill oil; n = 2 with placebo). Conclusions and Relevance: Among people with knee osteoarthritis who have significant knee pain and effusion-synovitis on magnetic resonance imaging, 2 g/d of daily krill oil supplementation did not improve knee pain over 24 weeks compared with placebo. These findings do not support krill oil for treating knee pain in this population. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12616000726459; Universal Trial Number: U1111-1181-7087.

Non-vertebral Mycobacterium avium complex osteomyelitis in an immunocompetent patient.

Mycobacterium avium complex (MAC) is a ubiquitous soil pathogen that is an uncommon cause of diseases in immunocompetent patients. In this case, we describe the presentation of an otherwise healthy man in his 50s presenting with months of malaise and severe hip pain, with aspiration initially yielding no bacteria and presumed fastidious infection. He was treated with irrigation and debridement, surgical stabilisation of the femoral neck and conventional broad-spectrum antibiotics with final cultures diagnostic of MAC osteomyelitis. This case serves to demonstrate the importance of clinical suspicion and appropriate workup of this unusual case of MAC hip osteomyelitis in an otherwise immunocompetent patient.

Clinical features of patients with hands arthralgia referred from primary care physicians to rheumatologists: A cohort study / Características clínicas de los pacientes con artralgia de manos que son referidos a la clínica de reumatología por médicos de atención primaria: un estudio de cohorte

Purpose: Early referral of patients with suspicious of rheumatoid arthritis (RA) has an impact on prognosis. Our study aimed to evaluate the clinical characteristics of patients with hands arthralgia who were referred from primary care physicians (PCP) to the rheumatologist.Methods: A descriptive, observational, prospective cohort study was performed. We included patients who visited a PCP for the first time for hands arthralgia. Demographics and the European Alliance of Associations for Rheumatology criteria for arthralgia suspicious for progression to RA plus seven complementary questions, the time to referral, the pressure needed to provoke pain with an automatic squeeze test machine in the metacarpophalangeal joints of both hands, and the diagnoses established at the last review of medical charts from patients on follow-up were documented. The primary outcome was the referral to a rheumatologist. Results: A total of 109 patients were included. The mean age was 49.9 years, 81.6% were women. 30.3% were referred to the rheumatologist. The time to referral was a median of 38 days. The main clinical characteristics associated with referral to the rheumatologist were the “most severe symptoms are present after midnight” (OR=6.29) and the “difficulty with making a fist” (OR=3.67). An isolated “positive squeeze test of metacarpophalangeal joints” was not associated with a referral to the rheumatologist. Conclusions: Among patients with hands arthralgia who attended PCP, those with most severe symptoms after midnight and difficulty making a fist were more likely to be referred to the rheumatology clinic. Isolated positive squeeze tests are not a parameter for referral, it should only be performed if arthralgia is clinically suspected.(AU)

Objetivo: Derivar tempranamente a los pacientes con sospecha de artritis reumatoide (AR) tiene un impacto en su pronóstico. Nuestro estudio tuvo como objetivo evaluar las características clínicas de los pacientes con artralgia de manos que fueron remitidos desde médicos de atención primaria (MAP) al reumatólogo. Métodos: Se realizó un estudio de cohorte descriptivo, observacional, y prospectivo. Incluimos pacientes que acudieron con un MAP por artralgia de manos. Se documentaron criterios demográficos y de la European Alliance of Associations for Rheumatology (EULAR) para artralgia con sospecha de progresión a AR más siete preguntas complementarias, el tiempo de derivación, la presión necesaria para provocar dolor con una máquina automática que comprime las articulaciones metacarpofalángicas, y los diagnósticos establecidos en la última revisión documentados en los expedientes médicos de los pacientes en seguimiento. El resultado principal fue la referencia al reumatólogo. Resultados: Un total de 109 pacientes fueron incluidos. El promedio de edad fue de 49,9 años, 81,6% fueron mujeres, 30,3% fueron referidos al reumatólogo. El tiempo de derivación al reumatólogo tuvo una mediana de 38 días. Las principales características clínicas asociadas con lo anterior fueron: «síntomas más severos presentes después de la medianoche» (OR=6,29) y «dificultad para hacer un puño» (OR=3,67). Una «prueba de compresión positiva de las articulaciones metacarpofalángicas» aislada no se asoció con una derivación al reumatólogo. Conclusión: Entre los pacientes que acudieron con MAP por artralgia de manos, aquellos con síntomas más severos después de la medianoche y que refirieron dificultad para realizar un puño fueron más frecuentemente referidos a una clínica de reumatología. Sin embargo, una prueba de compresión aislada no fue útil para la derivación temprana.(AU)

What factors influence pain scores following Corticosteroid injection in patients with Greater Trochanteric Pain Syndrome? A systematic review.

BACKGROUND: Cortico-Steroid Injections (CSI) are commonly used to treat patients with Greater Trochanteric Pain Syndrome (GTPS) but it is unclear which patients will experience improvements in pain. OBJECTIVES: To identify factors that influence improvements in pain for patients with GTPS treated with CSI. DESIGN: Systematic review. METHODS: A search was undertaken of AMED, CINAHL, Cochrane Library, EMBASE, Medline and PEDro databases. Studies were eligible for inclusion if they investigated factors that influenced changes in pain experienced by patients with GTPS who received a CSI. Studies needed to include relevant summary statistics and tests of clinical significance. Risk Of Bias in Non-randomised Trials Of Interventions (ROBINS-I) and Risk Of Bias 2 (ROB2) tools were used to assess bias. RESULTS: The search identified 466 studies, 8 were included in the final review with a total of 643 participants. There was no association between demographic variables such as age, sex, symptom duration or obesity and pain outcomes post-CSI. Having a co-existing musculoskeletal (MSK) condition such as knee osteoarthritis or sacroiliac/lumbar spine pain was associated with less pain reduction post-CSI. Injections into the Trochanteric Bursa were associated with longer lasting pain reduction than Gluteus Medius Bursa or extra-bursal injections. Image guidance of CSI maintained lower pain scores at six months but did not increase the duration of the therapeutic effect past six months. The presence of specific ultrasound scan features was not associated with differences in pain scores. CONCLUSIONS: Patients with co-existing MSK conditions may not respond to CSI as well as those without. Injections into the Greater Trochanteric Bursa may have longer lasting benefit. Further research is needed on the use of USS imaging findings and image guidance.

Single dose thermoresponsive dexamethasone prodrug completely mitigates joint pain for 15 weeks in a murine model of osteoarthritis.

In this study, we aimed to assess the analgesic efficacy of a thermoresponsive polymeric dexamethasone (Dex) prodrug (ProGel-Dex) in a mouse model of osteoarthritis (OA). At 12 weeks post model establishment, the OA mice received a single intra-articular (IA) injection of ProGel-Dex, dose-equivalent Dex, or Saline. Comparing to Saline and Dex controls, ProGel-Dex provided complete and sustained pain relief for >15 weeks according to incapacitance tests. In vivo optical imaging confirmed the continuous presence of ProGel-Dex in joints for 15 weeks post-injection. According to micro-CT analysis, ProGel-Dex treated mice had significantly lower subchondral bone thickness and medial meniscus bone volume than Dex and Saline controls. Except for a transient delay of body weight increase and slightly lower endpoint liver and spleen weights, no other adverse effect was observed after ProGel-Dex treatment. These findings support ProGel-Dex's potential as a potent and safe analgesic candidate for management of OA pain.

The Combined Intraosseous Administration of Orthobiologics Outperformed Isolated Intra-articular Injections in Alleviating Pain and Cartilage Degeneration in a Rat Model of MIA-Induced Knee Osteoarthritis.

BACKGROUND: Intra-articular (IA) platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) injections have shown efficacy and safety in treating osteoarthritis (OA). However, the effectiveness and mechanisms of combined intraosseous (IO) administration of these orthobiologics have yet to be explored. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the effect on pain, cartilage, synovium/infrapatellar fat pad (IFP), and subchondral bone in rat knee OA, comparing isolated IA with combined IA and IO (IA+IO) injections of PRP or BMAC. It was hypothesized that combined injections would be superior to sole IA injections. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 48 rats were divided into 6 groups: sham (only joint puncture during OA induction with IA+IO saline injection treatment) and 5 groups with OA induction, control (IA+IO saline injection), PRP (IA PRP+IO saline injection), BMAC IA (IA BMAC+IO saline injection), PRP IA+IO (IA+IO PRP injection), and BMAC IA+IO (IA+IO BMAC injection). OA was induced by IA injection of monosodium iodoacetate (MIA). Rats were administered different orthobiologics according to their grouping 3 weeks after the MIA injection. Pain changes were evaluated using the weightbearing ratio assay at weeks 3, 4, 5, 7, and 9 after OA induction. Rats were euthanized at week 9 for gross, radiological, histological, immunohistochemical, and immunofluorescence assessments of cartilage, synovium, and subchondral bone. RESULTS: Compared with the control group, all orthobiologics injection groups had reduced joint pain. Compared with IA injection, IA+IO injections provided superior pain relief by suppressing calcitonin gene-related peptide and substance P in both the synovium/IFP and subchondral bone. IA+IO injections slowed the progression of subchondral bone lesions by inhibiting CD31hiEmcnhi vessel formation and excessive osteoclast and osteoblast turnover while preserving subchondral bone microarchitecture, slowing cartilage degeneration. However, IA+IO injections did not outperform isolated IA injections in reducing synovitis and synovium/IFP fibrosis. Compared with PRP, BMAC exhibited superior inhibition of pain-related mediators, but no significant differences were observed in synovitis suppression, infrapatellar fat pad fibrosis, and subchondral bone protection. CONCLUSION: IA+IO injections of orthobiologics were more effective in relieving pain, slowing cartilage degeneration, and inhibiting abnormal vascularization and remodeling compared with isolated IA injections. BMAC showed superior pain relief in the synovium/IFP and subchondral bone compared with PRP. Further research is needed to optimize PRP and BMAC components for enhanced efficacy in OA management. CLINICAL RELEVANCE: Our findings contribute to advancing the understanding of pain relief mechanisms and support the endorsement of IO injection of orthobiologics for the treatment of OA and joint pain.

Randomized placebo-controlled, double-blind clinical trial of nanoemulsion curcumin in women with aromatase inhibitor-induced arthropathy: an Alliance/NCORP pilot trial.

PURPOSE: Aromatase inhibitor (AI) therapy reduces risk of recurrence and death for postmenopausal women with breast cancer (BC); however, AI-induced arthralgia (AIIA) can lead to discontinuation of treatment. Curcumin, a bioactive polyphenolic substance, may help ameliorate inflammation-related conditions including osteoarthritis and pain. METHODS: We conducted a multisite randomized placebo-controlled, double-blind pilot trial (Alliance A22_Pilot9) to evaluate the effects of nanoemulsion curcumin (NEC, 200 mg/day) in postmenopausal women experiencing AIIA for ≥ 3 months. The primary objective was to determine the feasibility of using Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) to detect changes from 0 (T0) to 3 months (T3) of NEC treatment in AI-induced symptoms and well-being; secondary objectives included evaluation of changes in Disabilities of the Shoulder, Arm, and Hand (DASH), Brief Pain Inventory-short form (BPI-SF), grip strength, and biomarkers at T0 and T3. RESULTS: Forty-two patients were randomized to NEC or placebo; 34 women completed the 3-month study. Patient-reported outcome measures (PROMs: FACT-ES, DASH, BPI-SF) and biospecimens were collected at T0-T3 in > 80% of participants. Adherence was ≥ 90% for both arms. PROMs and grip strength did not differ significantly by treatment arm. Plasma curcumin was detected only in NEC arm participants. Serum estradiol and estrone levels were below detection or low on study agent. Gastrointestinal adverse effects were commonly reported in both arms. CONCLUSION: NEC versus placebo in a multisite randomized trial is feasible and well-tolerated. Additional studies with larger sample size are needed to further evaluate the efficacy and safety of NEC in treatment of AIIA. CLINICALTRIALS: gov Identifier: NCT03865992, first posted March 7, 2019.

Potential Benefits of Psilocybin for Lupus Pain: A Case Report.

INTRODUCTION: Outcomes of treatment for patients with Lupus have shown overall improvement and benefit from the more aggressive use of immunosuppressants and biological agents through a treat-to-target approach. However, chronic musculoskeletal pain can be refractory to treatment despite the use of non-steroidal anti-inflammatory drugs, corticosteroids, and other analgesic agents, leading to patient dissatisfaction. The concept of new neural pathways from psilocybin usage has been proposed in a variety of pain syndromes; however, it is not trialed for patients with Lupus pain. CASE PRESENTATION: The patient was a 67-year-old male with positive anti-dsDNA antibody Lupus with a predominance of chronic polyarticular joint pain treated with hydroxychloroquine and non-steroidal anti-inflammatory drugs without pain relief. Pain dramatically improved after a one-time macro-dosing of 6 grams of Psilocybin cubensis in Oregon, which he expected would only provide a sense of enlightenment. After 12 months, he continued without debilitating joint pain. CONCLUSION: The serotonin-2A receptor's activation triggers an array of neurophysiological reactions that disrupt the functional connections in areas of the brain that are associated with chronic pain. These neuroplastic effects can generate healthy connections, resulting in long-lasting pain relief. However, this is a process that has not been fully analyzed. While there is anecdotal evidence to suggest the therapeutic benefits for autoimmune diseases, including rheumatoid arthritis and psoriasis, there is no specific research that explores its use for lupus-related pain. Since this is the first case that shows the benefit of psilocybin in a patient with Lupus, further studies on macro-dosing psilocybin to treat Lupus pain are warranted.

Successful complementary therapy with Chinese herbal medicine in a patient with refractory symptoms from systemic lupus erythematosus: A case report.

BACKGROUND: This study presents a unique case of a patient diagnosed with systemic lupus erythematosus and a relatively rare type of traditional Chinese medicine known as Qi deficiency and cold-dampness syndrome. The patient's condition was successfully treated using a combination of complementary therapies, specifically the modified Buzhong Yiqi decoction and the Erchen decoction. CASE PRESENTATION: A 34-year-old female patient experienced intermittent arthralgia and skin rash over three years. She also developed recurrent arthralgia and skin rashes in the last month, followed by low-grade fever, vaginal bleeding, alopecia, and fatigue. The patient was diagnosed with systemic lupus erythematosus and was prescribed prednisone, tacrolimus, anti-allergic medications (ebastine and loratadine), and norethindrone. While the arthralgia improved, the low-grade fever and rash persisted and, in some instances, worsened. Based on the evaluation of tongue coating and pulses, the patient's symptoms were attributed to Qi deficiency and cold-dampness syndrome. Consequently, the modified Buzhong Yiqi decoction and the Erchen decoction were added to her treatment regimen. The former was used to tonify Qi, while the latter was employed to resolve the phlegm dampness. As a result, the patient's fever subsided after three days, and all symptoms resolved within five days. CONCLUSION: The modified Buzhong Yiqi decoction and the Erchen decoction could be considered complementary therapy in systemic lupus erythematosus patients with Qi deficiency and cold-dampness syndrome.

A Blend of Tamarindus Indica and Curcuma Longa Extracts Alleviates Monosodium Iodoacetate (MIA)-Induced Osteoarthritic Pain and Joint Inflammation in Rats.

BACKGROUND AND OBJECTIVE: NXT15906F6 (TamaFlexTM) is a proprietary herbal composition containing Tamarindus indica seeds and Curcuma longa rhizome extracts. NXT15906F6 supplementation has been shown clinically effective in reducing knee joint pain and improving musculoskeletal functions in healthy and knee osteoarthritis (OA) subjects. The objective of the present study was to assess the possible molecular basis of the anti-OA efficacy of NXT15906F6 in a monosodium iodoacetate (MIA)-induced model of OA in rats. METHODS: Healthy male Sprague Dawley rats (age: 8-9 wk body weight, B.W.: 225-308 g (n = 12) were randomly assigned to one of the six groups, (a) vehicle control, (b) MIA control, (c) Celecoxib (10 mg/kg B.W.), (d) TF-30 (30 mg/kg B.W.), (e) TF-60 (60 mg/kg B.W.), and (f) TF-100 (100 mg/kg B.W.). OA was induced by an intra-articular injection of 3 mg MIA into the right hind knee joint. The animals received either Celecoxib or TF through oral gavage over 28 days. The vehicle control animals received intra-articular sterile normal saline. RESULTS: Post-treatment, NXT15906F6 groups showed significant (p < 0.05) dose-dependent pain relief as evidenced by improved body weight-bearing capacity on the right hind limb. NXT15906F6 treatment also significantly reduced the serum tumor necrosis factor-α (TNF-α, p < 0.05) and nitrite (p < 0.05) levels in a dose-dependent manner. mRNA expression analyses revealed the up-regulation of collagen type-II (COL2A1) and down-regulation of matrix metalloproteinases (MMP-3, MMP-9 and MMP-13) in the cartilage tissues of NXT15906F6-supplemented rats. Cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) protein expressions were down-regulated. Decreased immunolocalization of NF-κß (p65) was observed in the joint tissues of NXT15906F6-supplemented rats. Furthermore, microscopic observations revealed that NXT15906F6 preserved MIA-induced rats' joint architecture and integrity. CONCLUSION: NXT15906F6 reduces MIA-induced joint pain, inflammation, and cartilage degradation in rats.

Antiviral, Cytoprotective, and Anti-Inflammatory Effect of Ampelozizyphus amazonicus Ducke Ethanolic Wood Extract on Chikungunya Virus Infection.

Chikungunya fever, a debilitating disease caused by Chikungunya virus (CHIKV), is characterized by a high fever of sudden onset and an intense arthralgia that impairs individual regular activities. Although most symptoms are self-limited, long-term persistent arthralgia is observed in 30-40% of infected individuals. Currently, there is no vaccine or specific treatment against CHIKV infection, so there is an urgent need for the discovery of new therapeutic options for CHIKF chronic cases. This present study aims to test the antiviral, cytoprotective, and anti-inflammatory activities of an ethanol extract (FF72) from Ampelozizyphus amazonicus Ducke wood, chemically characterized using mass spectrometry, which indicated the major presence of dammarane-type triterpenoid saponins. The major saponin in the extract, with a deprotonated molecule ion m/z 897 [M-H]-, was tentatively assigned as a jujubogenin triglycoside, a dammarane-type triterpenoid saponin. Treatment with FF72 resulted in a significant reduction in both virus replication and the production of infective virions in BHK-21-infected cells. The viability of infected cells was assessed using an MTT, and the result indicated that FF72 treatment was able to revert the toxicity mediated by CHIKV infection. In addition, FF72 had a direct effect on CHIKV, since the infectivity was completely abolished in the presence of the extract. FF72 treatment also reduced the expression of the major pro-inflammatory mediators overexpressed during CHIKV infection, such as IL-1ß, IL-6, IL-8, and MCP-1. Overall, the present study elucidates the potential of FF72 to become a promising candidate of herbal medicine for alphaviruses infections.

Efficacy and safety of TRPV1-related preparations in the treatment of inflammatory arthralgia.

BACKGROUND: Currently, medications for the treatment of inflammatory arthralgia are limited. The role and safety of transient receptor potential vanilloid subtype 1 (TRPV1)-related preparations in reducing inflammatory arthralgia have not yet been fully established. Thus, we aimed to review the efficacy and safety of TRPV1-related preparations for the treatment of inflammatory arthralgia. METHODS: We searched PubMed, Web of Science, Cochrane, and Embase databases for relevant studies, and the primary outcome was pain score (VAS, PI, NRS, and WOMAC). RESULTS: Six randomized controlled trials involving 481 patients were analyzed. Patients with inflammatory arthralgia who received TRPV1-related preparations had lower pain scores after treatment than those who received placebo or nonsteroidal anti-inflammatory agents (standardized mean difference = -0.525; 95% confidence interval [CI], -0.789 to -0.261; P < .001). There was no significant difference in the incidence of total adverse reactions between the TRPV1-related preparations and control groups (relative risk = 1.225; 95% CI, 0.685 to 2.191; P = .494). CONCLUSION: TRPV1-related preparations are clinically safe and effective in the treatment of inflammatory arthralgia and are superior to placebo or nonsteroidal drugs. This may be the preferred treatment for patients with inflammatory arthralgia.