Rheumatoid Arthritis Pain Research Articles

P111 Reliability of quantitative sensory testing, disease activity score 28, ultrasound and central aspects of pain questionnaire in individuals with rheumatoid arthritis

Abstract Background/Aims Disease Activity Score 28 (DAS28), ultrasound, quantitative sensory testing (QST) and central aspect of pain (CAP) questionnaire measure disease activity and pain hypersensitivity. We investigated their inter-rater and test-retest reliability in Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA) participants. Methods Participants who attended the CAP-RA study visit and agreed to one or more reliability assessments were included. The same two raters completed all assessments, including clinical examination for DAS28, using a single blood sample per participant. QST modalities in the sequence: Pressure Pain detection Threshold (PPT) at the medial joint line of the most painful knee, tibialis anterior and contralateral brachioradialis, Temporal Summation (TS) at rectus femoris of the most painful knee and Conditioned Pain Modulation (CPM), with ischaemic arm pain conditioning and PPT at tibialis anterior. Ultrasound followed the Backhaus 7 protocol, plus the knee. Two trained sonographers scored each joint scan for grey scale (GS), power Doppler and a combined score (PDUS) using EULAR-OMERACT methodology. Joint scores were summated to give an overall score for GS, Doppler and PDUS. Participants could complete questionnaires at invitation, prior to and at baseline, 1-week post-baseline, prior to and at follow-up visit. Any combination of questionnaires completed within 7 days of each other assessed repeatability. Data were assessed for normality, interclass correlation coefficients, and Bland and Altman plots in R studio. Results 196 people were recruited into CAP-RA (median (IQR)) age 66 (58-75) y, 139 (75%) female, 190 (98%) white. 97 (49%) undertook study visits. Characteristics of the 66 people undertaking reliability did not significantly differ from the total population. Measurements are shown in Table 1. Moderate to excellent reliability was found across all measures except CPM (Table 1). The swollen joint count was the least reliable of the DAS28 components. Conclusion Measures of inflammatory disease activity and pain sensitivity are at least moderately reliable within a research context. Only low reliability for CPM might indicate imprecision, or reflect fluctuations in symptoms or pain sensitivity. High reliability of DAS28 and US might reflect relative stability of clinical signs of inflammation. Suppressing day-to-day fluctuations could reduce the unpredictability of rheumatoid arthritis. Disclosure S.L. Smith: None. V. Georgopoulos: None. O. Ifesemen: None. E. Ferguson: None. R.J. Wakefield: None. D. Wilson: None. P. Buckley: None. D. Platts: None. S. Ledbury: None. D.F. McWilliams: Grants/research support; Eli Lilly, Pfizer, GSK, Orion, UCB. D.A. Walsh: Grants/research support; Eli Lilly, Pfizer, GSK, Orion, UCB.

PEMANTAPAN CAREGIVER DALAM PELAYANAN KOMPLEMENTER PADA GERIATRI (PENDAMPINGAN SMK PUSAT KEJURUAN)

Introduction & Aim: Vocational High School (SMK) is a secondary education level organized to prepare graduates to enter the world of work. Vocational School's flagship program is to make graduates professional, ready, and skilled to synergize with the world of work, and are nursing assistants with specialization skills as caregivers. This community service activity aimed to strengthen alumni as caregivers through the Strengthening Caregivers in Complementary Services for Geriatric workshop. Method of Activity: the method of this community service activity is Participatory Action Research (PAR) with the form of activities What was carried out was a lecture and discussion on the topic of geriatric care and complementary cupping therapy, the activity continued with a simulation of the SOP for implementing cupping therapy and participant participation in cupping therapy activities at community service activities. about therapy in geriatrics and cupping training. The activity continued by involving students in cupping nursing therapy community service activities. Results: The community service activities of workshops, seminars, and complementary cupping therapy training ran smoothly, and were very relevant to the needs of SMK PK Bakti Indonesia Media alumni in providing services to the elderly. Discussion: Cupping therapy is relevant to the competency of vocational school graduates in providing services (caregivers) to the elderly. This is in accordance with the characteristics of Indonesian society, which is predominantly Muslim. Based on the results of community service activities, it was found that cupping therapy is effective for elderly people with hypertension, rheumatoid arthritis, gout, and bone pain. Cupping therapy competency can improve the quality of teaching factory implementation in vocational schools.

Ligustilide covalently binds to Cys703 in the pre-S1 helix of TRPA1, blocking the opening of channel and relieving pain in rats with acute soft tissue injury

Ethnopharmacological relevanceThe natural anodyne Ligustilide (Lig), derived from Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort., has been traditionally employed for its analgesic properties in the treatment of dysmenorrhea and migraine, and rheumatoid arthritis pain. Despite the existing reports on the correlation between TRP channels and the analgesic effects of Lig, a comprehensive understanding of their underlying mechanisms of action remains elusive. Aim of the studyThe objective of this study is to elucidate the mechanism of action of Lig on the analgesic target TRPA1 channel. MethodsThe therapeutic effect of Lig was evaluated in a rat acute soft tissue injury model. The analgesic target was identified through competitive inhibition of TRP channel agonists at the animal level, followed by Fluo-4/Ca2+ imaging on live cells overexpressing TRP proteins. The potential target was verified through in-gel imaging, colocalization using a Lig-derived molecular probe, and a drug affinity response target stability assay. The binding site of Lig was identified through protein spectrometry and further analyzed using molecular docking, site-specific mutation, and multidisciplinary approaches. ResultsThe administration of Lig effectively ameliorated pain and attenuated oxidative stress and inflammatory responses in rats with soft tissue injuries. Moreover, the analgesic effects of Lig were specifically attributed to TRPA1. Mechanistic studies have revealed that Lig directly activates TRPA1 by interacting with the linker domain in the pre-S1 region of TRPA1. Through metabolic transformation, 6,7-epoxyligustilide (EM-Lig) forms a covalent bond with Cys703 of TRPA1 at high concentrations and prolonged exposure time. This irreversible binding prevents endogenous electrophilic products from entering the cysteine active center of ligand-binding pocket of TRPA1, thereby inhibiting Ca2+ influx through the channel opening and ultimately relieving pain. ConclusionsLig selectively modulates the TRPA1 channel in a bimodal manner via non-electrophilic/electrophilic metabolic conversion. The epoxidized metabolic intermediate EM-Lig exerts analgesic effects by irreversibly inhibiting the activation of TRPA1 on sensory neurons. These findings not only highlight the analgesic mechanism of Lig but also offer a novel nucleophilic attack site for the development of TRPA1 antagonists in the pre-S1 region.

Synovial fibroblast gene expression is associated with sensory nerve growth and pain in rheumatoid arthritis.

It has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal that pain scores in patients do not correlate with synovial inflammation. We developed a machine-learning approach (graph-based gene expression module identification or GbGMI) to identify an 815-gene expression module associated with pain in synovial biopsy samples from patients with established RA who had limited synovial inflammation at arthroplasty. We then validated this finding in an independent cohort of synovial biopsy samples from patients who had early untreated RA with little inflammation. Single-cell RNA sequencing analyses indicated that most of these 815 genes were most robustly expressed by lining layer synovial fibroblasts. Receptor-ligand interaction analysis predicted cross-talk between human lining layer fibroblasts and human dorsal root ganglion neurons expressing calcitonin gene-related peptide (CGRP+). Both RA synovial fibroblast culture supernatant and netrin-4, which is abundantly expressed by lining fibroblasts and was within the GbGMI-identified pain-associated gene module, increased the branching of pain-sensitive murine CGRP+ dorsal root ganglion neurons in vitro. Imaging of solvent-cleared synovial tissue with little inflammation from humans with RA revealed CGRP+ pain-sensing neurons encasing blood vessels growing into synovial hypertrophic papilla. Together, these findings support a model whereby synovial lining fibroblasts express genes associated with pain that enhance the growth of pain-sensing neurons into regions of synovial hypertrophy in RA.

Pemanfaatan Lingkungan Sekitar Dalam Pengembangan Masyarakat Yang Sehat Dan Berkemajuan Saga ( Sahabat Keluarga) Di Desa Batubelah

In treating wounds and reducing rheumatic pain, many methods have been developed, one of which is the herbal treatment method. One of the plants used to treat wounds is betel leaves and olive oil and ginger juice. This service method is (1) Preparatory stage Forming an activity committee: Coordinating to determine the time for the meeting. Prepare a proposal (pre planning). Carry out the guidance process for implementing Herbal Space procurement activities. (2) Carrying out activities by creating a Herbal Space in the Community. In this service, the results of non-pharmacological treatment carried out by researchers were the use of olive oil and ginger juice. Ginger has many benefits, namely it can reduce pain in joint pain or rheumatoid arthritis. The content of this olive oil is oleocanthal which can function similarly to ibuprofen, namely anti-inflammatory. Apart from that, olive oil also contains prostaglandins which can be used to reduce swelling and joint pain in rheumatoid arthritis sufferers. There is an effect of giving crushed betel leaves to accelerate the healing process of incisional wounds in the community so it is hoped that betel leaves will be used as an alternative for wound healing with non-pharmacological or herbal treatments.

The effectiveness and safety of lifestyle medicine and integrative therapies in inflammatory arthritis: an umbrella review using a hierarchical evidence gathering approach.

An umbrella review was conducted to provide a comprehensive evaluation of the evidence on lifestyle medicine and integrative therapies for inflammatory arthritis. Five electronic databases were searched for umbrella reviews, meta-analyses, and systematic reviews of randomised controlled trials on acupuncture, diet, exercise, herbal medicine, nutrient supplements, and mind-body therapies for rheumatoid arthritis, spondyloarthritis, and gout published from January 2012 to December 2022. The primary outcomes were functional status and quality of life. Quality assessment was performed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) tool, and the certainty of evidence for our primary outcomes was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach where possible. We included 52 reviews. Exercise was beneficial for functional status in both rheumatoid arthritis and spondyloarthritis, with moderate certainty of evidence. Chinese herbal medicine in combination with disease-modifying anti-rheumatic drugs may improve functional status in rheumatoid arthritis (very low certainty evidence). Acupuncture may improve functional status in rheumatoid arthritis and pain in both rheumatoid arthritis and gout; however, the evidence is of very low certainty. Evidence for other therapies was not clinically significant; however, it suggests possible benefits from quercetin and polyunsaturated fatty acids. Yoga may result in a moderate improvement in functional status when used as an adjunct to medication; however, the certainty of evidence is very low. Diet interventions offered inconsistent improvements to functional status in rheumatoid arthritis, spondyloarthritis, and gout with low to very low certainty. Exercise should be prescribed for people with rheumatoid arthritis and spondyloarthritis. More research is needed to confirm or refute evidence for Chinese herbal medicine, acupuncture, yoga, and anti-inflammatory diets.

Dukungan Keluarga, Karakteristik dan Efektivitas Kompres Hangat Kayu Manis terhadap Penurunan Skala Nyeri Rheumatoid Arthritis

This study aims to identify and analyze the influence of family support before and after the action, the characteristics of family members, the influence of the action, and the effectiveness of the action of warm cinnamon and warm compresses on reducing the pain scale for rheumatoid arthritis. This research method is quantitative with a quasi-experimental research design using a pre-test and post-test design with a warm compress control group. The sampling method in this study used total sampling, so the number of samples for each group was: 30 people for the control group and 30 people for the intervention group. This research began in September 2023 – February 2024. Based on the results of statistical tests using the Mann-Whitney and Wilcoxon tests, the P-value was obtained, namely 0.000 < α = 0.05. In conclusion, there is the influence of family support before and after the action is taken, there is the influence of warm cinnamon compresses and warm compresses, then there is the effectiveness of warm cinnamon compresses and warm compresses on reducing the scale of rheumatoid arthritis pain. Keywords: Warm Cinnamon Compress, Pain, Rheumatoid Arthritis.

In Vitro and Biological Evaluation of Oral Fast-Disintegrating Films Containing Ranitidine HCl and Syloid® 244FP-Based Ternary Solid Dispersion of Flurbiprofen.

Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), is commonly used to treat the pain of rheumatoid arthritis, but in prolonged use it causes gastric irritation and ulcer. To avoid these adverse events of NSAIDs, the simultaneous administration of H2 receptor antagonists such as ranitidine hydrochloride (RHCl) is obligatory. Here, we developed composite oral fast-disintegrating films (ODFs) containing FBP along with RHCl to provide a gastroprotective effect as well as to enhance the solubility and bioavailability of FBP. The ternary solid dispersion (TSD) of FBP was fabricated with Syloid® 244FP and poloxamer® 188 using the solvent evaporation technique. The synthesized FBP-TSD (coded as TSD) was loaded alone (S1) and in combination with plain RHCl (S2) in the composite ODFs based on hydroxypropyl methyl cellulose E5 (HPMC E5). The synthesized composite ODFs were evaluated by in vitro (thickness, folding endurance, tensile strength, disintegration, SEM, FTIR, XRD and release study) and in vivo (analgesic, anti-inflammatory activity, pro-inflammatory cytokines and gastroprotective assay) studies. The in vitro characterization revealed that TSD preserved its integrity and was effectively loaded in S1 and S2 with optimal compatibility. The films were durable and flexible with a disintegration time ≈15 s. The release profile at pH 6.8 showed that the solid dispersion of FBP improved the drug solubility and release when compared with pure FBP. After in vitro studies, it was observed that the analgesic and anti-inflammatory activity of S2 was higher than that of pure FBP and other synthesized formulations (TSD and S1). Similarly, the level of cytokines (TNF-α and IL-6) was also markedly reduced by S2. Furthermore, a gastroprotective assay confirmed that S2 has a higher safety profile in comparison to pure FBP and other synthesized formulations (TSD and S1). Thus, composite ODF (S2) can effectively enhance the FBP solubility and its therapeutic efficacy, along with its gastroprotective effect.

SOCIAL NETWORK BARRIERS AND FACILITATORS TO RHEUMATOID ARTHRITIS MANAGEMENT IN HISPANIC/LATINX FAMILIES

Abstract Compared to their non-Hispanic White counterparts, individuals of Hispanic/Latinx heritage are more likely to develop disabilities from comorbidity and remain disabled for longer periods over the life course. Among chronic conditions, rheumatoid arthritis (RA) is very common, affecting at least 1% of the U.S. population. Evidence suggests that RA is more active and severe among Hispanic/Latinx individuals, characterized by more flare-ups, greater inflammation, higher tender/swollen joint counts, and more self-reported pain, due in part to their underuse of health services, delay in initiating treatment, and difficulty in adhering to treatment plan. In this study, we sought to identify social network factors relevant to managing RA pain and RA-attributable functional limitations, in a sample of Hispanic/Latinx families residing in the Washington DC region. We analyzed network structure and patterns of interpersonal health communication and assessed how these factors may facilitate or impede proactive healthcare, independent of individual and system-level barriers. The findings are three-fold: First, there is substantial heterogeneity in social network structure in the families examined, likely due to different immigration experiences. Second, severely contracted personal networks (e.g., isolate or singe-edge) were observed among older, foreign-born individuals who spoke Spanish and had less schooling. This was a major barrier to RA management. Finally, more health communication, closeness, and advice-seeking ties in one’s personal network facilitated use of health services which was positively correlated with health outcomes. We discuss the implications of the findings in the context of developing family network-based health education interventions.

The interrater and test-retest reliability of 3 modalities of quantitative sensory testing in healthy adults and people with chronic low back pain or rheumatoid arthritis.

Quantitative Sensory Testing (QST) modalities used to assess central pain mechanisms require different protocols in people with different musculoskeletal conditions. We aimed to explore the possible effects of musculoskeletal diagnosis and test site on QST interrater and test-retest reliability. The study included participants with rheumatoid arthritis (RA, n = 18; QST conducted on lower leg) and low back pain (LBP, n = 25; QST conducted on forearm), plus 45 healthy control participants (n = 20 QST on lower leg and n = 25 QST on forearm). Test-retest reliability was assessed from QST conducted 1 to 3 weeks apart. Quantitative sensory testing modalities used were pressure pain detection threshold (PPT) at a site distant to tissue pathology, temporal summation (TS), and conditioned pain modulation (CPM). Temporal summation was calculated as difference or ratio of single and repeated punctate stimuli and unconditioned thresholds for CPM used single or mean of multiple PPTs. Intraclass correlation coefficients (ICCs) were compared between different subgroups. High to very high reliability was found for all assessments of PPT and TS across anatomical sites (lower leg and forearm) and participants (healthy, RA, and LBP) (ICC ≥ 0.77 for PPT and ICC ≥ 0.76 for TS). Reliability was higher when TS was calculated as a difference rather than a ratio. Conditioned pain modulation showed no to moderate reliability (ICC = 0.01-0.64) that was similar between leg or forearm, and between healthy people and those with RA or LBP. PPT and TS are transferable tools to quantify pain sensitivity at different testing sites in different musculoskeletal diagnoses. Low apparent reliability of CPM protocols might indicate minute-to-minute dynamic pain modulation.

Nanomaterials as catalysts for the sensitive and selective determination of diclofenac.

Diclofenac (DCF) is a non-steroidal anti-inflammatory drug possessing analgesic and antipyretic properties. It is used for the treatment of rheumatoid arthritis pain, osteoarthritis, and acute muscle pain conditions and can be administrated orally, topically or intravenously. Because of its widespread use, hydrophilicity, stability and poor degradation (bioaccumulation in the food chain), DCF is an emerging chemical contaminant that can cause adverse effects in the ecosystems. Taking into account the consumption of DCF in pharmaceutical formulations and its negative impact on the environment, the development of new sensitive, selective, cheap, fast, and online capable analytical devices is needed for on-site applications. This brief review attempts to cover the recent developments related to the use of nanomaterials as catalysts for electrochemical determination of DCF in pharmaceutical formulations, biological fluids and environmental samples. The article aims to prove how electrochemical sensors represent reliable alternatives to conventional methods for DCF analysis. The manuscript highlights the progress in the development of electrochemical sensors for DCF detection. We have analyzed numerous recent papers (mainly since 2019) on sensors developed for the quantitative determination of DCF, indicating the limit of detection, linear range, stability, reproducibility, and analytical applications. Current challenges related to the sensor design and future perspectives are outlined.

KARAKTERISASI DAN OPTIMASI EMULGEL NA DIKLOFENAK DENGAN METODE SIMPLEX LATTICE DESIGN

Diclofenac Na is an NSAID class of drugs that functions to treat pain and inflammation of rheumatoid arthritis, osteoarthritis or joint disease. The aim of this study is to investigate the effect of carbopol 940, HPMC K15M and propyleneglycol variations on the emulgel physical properties, carbopol concentration, HPMC, propyleneglycol to produce an optimum formula.The method used in this optimization is Simplex Lattice Design. The independent variables which include carbopol 490 , HPMC K15M , propylene glycol were then included in the expert design to obtain 16 runs. Each formula was tested for viscosity, spreadability, adhesion, pH, diffusivity and physical stability. Each parameter has a contour plot and by superimposing it can be determined the shaded area which is the area of ​​the optimum formula. The optimum formula was carried out using a one sample t-test with a 95% confidence level. Based on the results of superimposed superimposed graphic observations for the manufacture of diclofenac narium emulgel with test parameters including spreadability, viscosity, adhesion, PH, diffusion ability and stability test, the composition of Carbobol 940 0.5 - 1.22%, HPMC K-15M 3.24 - 3.77 Propylene glycol 5 - 6.26%. The results of the t-test showed that the Simplex Lattice Design equation in the formula showed results that were not significantly different, this shows the significance value of the results before treatment with treatment results > 0.05. This shows that the equation is valid and the stability test is stable.

A concept elicitation study to understand the relationship between sleep and pain in rheumatoid arthritis and axial spondyloarthritis

PurposeThis qualitative study (GSK study: 213635) was designed to better understand sleep disturbance as experienced by individuals with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA), and the relationship between sleep disturbance and pain and other aspects of the disease and disease activity.MethodsSixty-minute, one-on-one, concept elicitation interviews were conducted with 30 participants (15 with RA and 15 with axSpA) from the US. Interviews were audio-recorded and transcribed verbatim. Interview transcripts were coded and analyzed to explore themes related to pain and sleep disturbance, and relationships among those themes.ResultsPain was a prominent driver of sleep disturbance; 12 participants with RA (80%) and 14 with axSpA (93%) reported that pain impacted their ability to fall asleep, while all 15 with RA (100%) and 14 with axSpA (93%) reported that pain impacted their ability to stay asleep. Two-thirds of participants with RA (67%) or axSpA (60%) described a bi-directional relationship, whereby pain worsened sleep disturbance and sleep disturbance further aggravated pain. Factors other than pain, such as fatigue and emotional health, were also reported as important contributors to sleep disturbance (RA: n = 12/15, 80%; axSpA: n = 14/15, 93%). Participants with RA or axSpA described complex interconnections between fatigue, emotional health, pain, and sleep, often labeling these relationships as “vicious cycles”. Notably, half of all participants reported sleep disturbance occurring without pain or other understood causes.ConclusionThese perspectives collected from people with RA or axSpA suggest that reducing sleep disruption directly may offer clinically relevant benefits.

Prevalence and Characteristics of Knee Osteoarthritis Among the General Public in Saudi Arabia.

Background Knee osteoarthritis (OA) is a chronic and progressive knee joint condition that is influenced by multiple factors. This research aims to examine the prevalence and characteristics of knee OA among the general public in Saudi Arabia. Methodology This cross-sectional online survey was conducted in September 2023 in Saudi Arabia. This research used a previously developed questionnaire to validate the diagnosis of OA, which was performed in accordance with the diagnostic criteria established by the American College of Rheumatology (ACR). The Western Ontario and McMaster Universities Arthritis Index questionnaire (WOMAC) was used to examine the severity and characteristics of knee OA patients. A binary logistic regression analysis was conducted to determine the variables that influence the severity of knee OA and the likelihood of developing OA. Results A total of 1,019 individuals participated in this study. Around one-third of the participants (34.5%) fulfilled the ACR criteria for knee OA diagnosis. Overall, the mean WOMAC score was 34.1 (18.8) out of 96, which represents 35.5% of the maximum obtainable score and demonstrates a low degree of knee OA severity. The mean pain sub-scale score was 7.4 (3.8) out of 20, which represents 37.0% of the maximum obtainable score and demonstrates a low level of pain intensity. The mean stiffness sub-scale score was 2.7 (1.8) out of 8, which represents 33.8% of the maximum obtainable score and demonstrates a low degree of stiffness in joints. The mean physical function sub-scale score was 24.0 (14.0) out of 68, which represents 35.3% of the maximum obtainable score and demonstrates a low level of physical function difficulty. Females, older participants (above 40 years), those with high body mass index (28.8 kg/cm2 and higher), non-smokers, those with comorbidities, those who did not practice daily physical activity, those who had a family history of knee OA, and those who suffered from flat feet, rheumatoid arthritis, gout, lupus, or back or hip pain were more likely to develop knee OA and have severe OA (p < 0.05). Conclusions Thefindings of this study demonstrated a significant prevalence rate of kneeOA and highlighted a discrepancy between the rates obtained by diagnostic criteria and those determined through clinical diagnosis. Several significant factors that contribute to the development of OAencompass lifestyle choices such as food and exercise, familial predisposition, genetic influences, and the presence of comorbidities. To effectively tackle this intricate matter, it is imperative to adopt a patient-centered strategy and prioritize early intervention.

The effects of Phycocyanobilin on experimental arthritis involve the reduction in nociception and synovial neutrophil infiltration, inhibition of cytokine production, and modulation of the neuronal proteome.

The antinociceptive and pharmacological activities of C-Phycocyanin (C-PC) and Phycocyanobilin (PCB) in the context of inflammatory arthritis remain unexplored so far. In the present study, we aimed to assess the protective actions of these compounds in an experimental mice model that replicates key aspects of human rheumatoid arthritis. Antigen-induced arthritis (AIA) was established by intradermal injection of methylated bovine serum albumin in C57BL/6 mice, and one hour before the antigen challenge, either C-PC (2, 4, or 8 mg/kg) or PCB (0.1 or 1 mg/kg) were administered intraperitoneally. Proteome profiling was also conducted on glutamate-exposed SH-SY5Y neuronal cells to evaluate the PCB impact on this key signaling pathway associated with nociceptive neuronal sensitization. C-PC and PCB notably ameliorated hypernociception, synovial neutrophil infiltration, myeloperoxidase activity, and the periarticular cytokine concentration of IFN-γ, TNF-α, IL-17A, and IL-4 dose-dependently in AIA mice. In addition, 1 mg/kg PCB downregulated the gene expression for T-bet, RORγ, and IFN-γ in the popliteal lymph nodes, accompanied by a significant reduction in the pathological arthritic index of AIA mice. Noteworthy, neuronal proteome analysis revealed that PCB modulated biological processes such as pain, inflammation, and glutamatergic transmission, all of which are involved in arthritic pathology. These findings demonstrate the remarkable efficacy of PCB in alleviating the nociception and inflammation in the AIA mice model and shed new light on mechanisms underlying the PCB modulation of the neuronal proteome. This research work opens a new avenue to explore the translational potential of PCB in developing a therapeutic strategy for inflammation and pain in rheumatoid arthritis.

Impact of humid climate on rheumatoid arthritis faecal microbiome and metabolites

Studies have shown that high humidity is a condition that aggravates the pain of rheumatoid arthritis (RA), but the relevant mechanism is controversial. Currently, there is a lack of experimental animal studies on high humidity as an adverse factor related to the pathogenesis of RA. We used healthy SD rats and collagen-induced arthritis (CIA) rats to investigate the effects of high humidity on arthritis. Integrated metabolomics analyses of faeces and 16S rRNA sequencing of the faecal microbiota were performed to comprehensively assess the diversity of the faecal microbiota and metabolites in healthy and CIA rats. In this study, high humidity aggravated arthritis in CIA rats, which manifested as articular cartilage lesions, increased arthritis scores, and an increase in proinflammatory cytokines. High humidity had a certain effect on the articular cartilage extent, arthritis score and proinflammatory cytokines of healthy rats as well. Furthermore, high humidity caused significant changes in faecal microbes and metabolites in both healthy and CIA rats. 16S rRNA sequencing of faecal samples showed that high humidity increased the amount of inflammation-related bacteria in healthy and CIA rats. Faecal metabolomics results showed that high humidity significantly altered the level of faecal metabolites in healthy rats and CIA rats, and the changes in biological functions were mainly related to the inflammatory response and oxidative stress. Combined analysis showed that there was a strong correlation between the faecal microbiota and faecal metabolites. High humidity is an adverse factor for the onset and development of RA, and its mechanism is related to the inflammatory response and oxidative stress. However, the question of how high humidity impacts RA pathogenesis needs to be further investigated.

Exploring the Novel Dimension of Immune Interactions in Pain: JAK Inhibitors' Pleiotropic Potential.

This review explores the link between immune interactions and chronic pain, offering new perspectives on treatment. It focuses on Janus kinase (JAK) inhibitors' potential in pain management. Immune cells' communication with neurons shapes neuroinflammatory responses, and JAK inhibitors' effects on pain pathways are discussed, including cytokine suppression and microglial modulation. This review integrates studies from rheumatoid arthritis (RA) pain and central sensitization to highlight connections between immune interactions and pain. Studies on RA joint pain reveal the shift from cytokines to sensitization. Neurobiological investigations into central sensitization uncover shared pathways in chronic pain. Clinical evidence supports JAK inhibitors' efficacy on pain-related outcomes and their effects on neurons and immune cells. Challenges and future directions are outlined, including interdisciplinary collaboration and dosing optimization. Overall, this review highlights JAK inhibitors' potential to target immune-mediated pain pathways, underscoring the need for more research on immune-pain connections.

The burden of rheumatoid arthritis and low back pain in North Africa and Middle East from 1990 to 2019: Results from the Global Burden of Disease Study 2019.

Rheumatoid arthritis (RA) and low back pain (LBP) are among the most prevalent musculoskeletal disorders (MSDs). The need for investigation of regional and local patterns of these two MSDs seems inevitable for better policy-making. The current study presents updated results of the Global Burden of Disease (GBD) Study 2019 and reports the burden of RA and LBP in North Africa and Middle East (NAME) countries from 1990 to 2019. Incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and risk factors, including high body mass index, occupational ergonomic factors, and smoking, were extracted based on the GBD 2019 data. The age-standardized prevalence and mortality of RA were 120.6 (95% uncertainty interval [95% UI] 107.0-135.7) and 0.1 (95% UI 0.1-0.2) per 100 000 population in 2019 with 28.3% (95% UI 25.5%-30.9%) increase and 7.5% (95% UI -37.5% to 32.5%) decrease since 1990, respectively. Turkey had the highest age-standardized incidence, prevalence, and DALYs of RA in 2019. All RA burden measures were higher for women; however, the incidence was almost the same at ages greater than 65 years. The age-standardized prevalence and DALYs of LBP were 7668.2 (95% UI 6798.0-8636.3) and 862 (95% UI 605.5-1153.3) in 2019, which had decreased by 5.8% (95% UI -7.4% to -4.3%) and 6.0% (95% UI -7.7% to -4.2%) since 1990, respectively. Moreover, although Turkey had the highest incidence and prevalence in 1990, Iran was at the top in 2019. The regional age-standardized DALY rates due to RA and LBP attributed to smoking were 1.7 (95% UI 0.5-3.2) and 139.4 (95% UI 87.3-198.8) in 2019, respectively, which had decreased 2.2% (95% UI -19.2% to 13.7%) and 15.4% (95% UI -19.4% to -10.5%) since 1990, respectively. RA still imposes a significant burden in the NAME region as the burden measures have increased from 1990 to 2019. On the other hand, regarding LBP, a decreasing pattern was observed. Differences among the countries and between ages and genders can have implications, and the results of this study may be helpful for policy-makers in the NAME countries.

Examining pain severity in women with rheumatoid arthritis: the impact of pain self-efficacy and perceived partner's emotional support.

Empirical data suggest that psychosocial factors, such as pain self-efficacy (PSE) and emotional support from a partner, may alleviate the suffering caused by rheumatoid arthritis (RA) pain. However, the data are ambiguous and warrant a more comprehensive investigation into the effect of these factors on the severity of RA pain. The objective of the present study was to assess the significance of PSE and emotional support from a partner in relation to pain severity among women with RA. The study included a sample of 196 women diagnosed with RA with the mean age of 41.54. The study employed the following measures: Rheumatoid Arthritis Pain Scale, Pain Self-efficacy Questionnaire, and Communication Based Emotional Support Scale. The analysis revealed that higher PSE emerged as the strongest predictor for lower pain severity across all components of RA pain. However, the impact of the partner's emotional support on pain severity was not as evident and varied depending on the specific pain component. Furthermore, the use of pain medications significantly predicted three out of four pain components. Mediation analysis revealed that perceived emotional support from a partner directly affected women's RA pain intensity, as well as indirectly through the PSE as a mediator. Moderated mediation analysis demonstrated that the association between PSE and pain severity weakened as the duration of RA increased. Enhancing women's PSE and providing appropriate training for their partners to offer effective emotional support may play a crucial role in the treatment of RA.

How do symptoms of each joint contribute to global pain, disease activity and functional disability in rheumatoid arthritis?-A comprehensive association study using a large cohort.

Established assessment tools for patients with rheumatoid arthritis (RA), including disease activity scores (DASs), disease activity indexes (DAIs), visual analog scales (VASs), and health assessment questionnaires (HAQs), are widely used. However, comparative associations between joint involvement and disease status assessment tools have rarely been investigated. We included a dataset of 4016 patients from a large RA cohort from 2012 to 2019. The tenderness and swelling of each joint were counted as a symptom, with 70 and 68 affected joints throughout the body, respectively. The relative contribution of various joints to the disease status assessment tools, VAS scores, and functional disability indexes was analyzed using multiple regression analysis. The wrist showed the most significant contribution overall, especially in DASs and VASs, while the metacarpophalangeal and proximal interphalangeal joints made significant contributions to DASs and DAIs, but not to VASs and HAQs. The shoulder and the elbow significantly contributed to HAQs, but only the shoulder did to the VASs. The knee universally contributed to all of the tools, but the ankle played a minor but important role in most assessment tools, especially in HAQs. Similar but different contribution ratios were found between the sets of DASs, DAIs, VASs, or HAQs. Each joint makes a unique contribution to these assessment tools. The improvement or aggravation of symptoms in each joint affects the assessment tools in different manners.