Rheumatoid Arthritis Pain Research Articles

Transcriptome analysis of rheumatoid arthritis uncovers genes linked to inflammation-induced pain

Autoimmune diseases such as rheumatoid arthritis (RA) can promote states of chronic inflammation with accompanying tissue destruction and pain. RA can cause inflammatory synovitis in peripheral joints, particularly within the hands and feet, but can also sometimes trigger temporomandibular joint (TMJ) arthralgia. To better understand the effects of ongoing inflammation-induced pain signaling, dorsal root ganglia (DRGs) were acquired from individuals with RA for transcriptomic study. We conducted RNA sequencing from the L5 DRGs because it contains the soma of the sensory neurons that innervate the affected joints in the foot. DRGs from 5 RA patients were compared with 9 non-arthritic controls. RNA-seq of L5 DRGs identified 128 differentially expressed genes (DEGs) that were dysregulated in the RA subjects as compared to the non-arthritic controls. The DRG resides outside the blood brain barrier and, as such, our initial transcriptome analysis detected signs of an autoimmune disorder including the upregulated expression of immunoglobulins and other immunologically related genes within the DRGs of the RA donors. Additionally, we saw the upregulation in genes implicated in neurogenesis that could promote pain hypersensitivity. Overall, our DRG analysis suggests that there are upregulated inflammatory and pain signaling pathways that can contribute to chronic pain in RA.

Patient-Reported Outcomes of Pain, Stiffness, and Fatigue Reduction in Rheumatoid and Psoriatic Arthritis With Cannabinoid Use

Patient-Reported Outcomes of Pain, Stiffness, and Fatigue Reduction in Rheumatoid and Psoriatic Arthritis With Cannabinoid Use

Unmet Needs in Spondyloarthritis: Understanding and Managing Chronic Pain.

Among patients with axial spondyloarthritis (axSpA), persistent pain remains a critical unmet need. In this review, we discuss the prevalence of chronic pain and fibromyalgia in patients with axSpA and examine the existing knowledge on the pathophysiology of chronic pain in SpA, osteoarthritis, and rheumatoid arthritis. Finally, we discuss the specific unmet needs that must be addressed to improve long-term outcomes in axSpA, specifically those that will improve chronic pain in this patient population.

Disability Related to the Upper Extremities in Early Rheumatoid Arthritis-Long-Term Course and Disease Variable Impact: A Cohort Study.

To investigate the course of disability related to the upper extremities (UEs) in early rheumatoid arthritis (RA), and to assess correlations between such disability and clinical variables, including grip force. In an inception cohort of patients with early RA (diagnosed 1995-2005, N = 222, follow-up 10 yrs), disability of the UEs was assessed using a subscore of the Health Assessment Questionnaire-Disability Index (HAQ-DI-UE), and average grip force of the dominant hand was measured. Changes between consecutive follow-up visits in the HAQ-DI-UE subscore, and correlations at each visit with key clinical variables, were assessed. The relation between joint involvement and HAQ-DI-UE was examined using multivariate linear regression analysis. The HAQ-DI-UE decreased significantly from inclusion to the 6-month follow-up (mean change -0.26, 95% CI -0.18 to -0.34), and increased significantly after 2 years. There were fairly strong correlations for HAQ-DI-UE with grip force (r = -0.50 to -0.62), patient global assessment (r = 0.53 to 0.64), and patient-reported pain (r = 0.54 to 0.60) at all timepoints through 5 years, but only moderate to weak correlations with swollen joints, C-reactive protein, and erythrocyte sedimentation rate. At inclusion, wrist synovitis and tender proximal interphalangeal joints both had an independent effect on HAQ-DI-UE, whereas tenderness of the shoulder and the wrist had a greater importance at 6 months. Disability related to the UEs decreased significantly during the first 6 months, and increased again after 2 years. The correlations with clinical variables underline the major effect of pain and impaired hand function in early RA.

Pain in Biologic-Treated Rheumatoid Arthritis Patients: The Role of Illness Perception Before and After the COVID-19 Pandemic.

We aimed to assess the role of the COVID-19 pandemic in the association of clinical, physical, and psychological factors with pain in Rheumatoid Arthritis (RA) patients. We included 103 RA patients (81.6% females; mean age 56.1±13.8years). Patients filled out the VAS-pain, GAD-7, PHQ-9, MFI-20, and B-IPQ. Paired sample t-tests, correlations, and multiple regression analyses were used to analyse the data. Our results showed significantly worsened pain in the data collected post-pandemic (p≤0.05). Pre-pandemic, the final regression models showed an association between functional disability (β=0.24; p≤0.05), illness perception (β=0.34; p≤0.05) and pain. In post-pandemic models, significant associations were found between fatigue (β=0.33; p≤0.01) and illness perception (β=0.36; p≤0.01) with pain. Positive illness perception was able to alleviate the associations between fatigue and depression with pain before and after the pandemic. Findings indicate that patients with RA may have been negatively affected by the COVID-19 pandemic given their vulnerability. Even though pharmacological treatment was not interrupted, post-pandemic results showed significantly higher levels of experienced pain. Therefore, in addition to biological therapy, non-pharmacological interventions, including psychological support aimed at diminishing negative illness perception, may be beneficial in reducing RA-related pain, especially when dealing with a crisis.

Effect of Foot Orthoses and Footwear in People with Rheumatoid Arthritis: An Updated Systematic Review.

Rheumatoid arthritis is a chronic, systemic, inflammatory disease of an autoimmune nature that causes pain and disability in affected patients. Foot pain has become a challenge due to its negative impact on physical function. The objective of this updated systematic review is to describe the effect of foot orthoses and/or footwear in patients with rheumatoid arthritis and foot problems. Scopus, PubMed, CINALH, WOS, and Dialnet were searched for all articles published from January 2013 to September 2024. Inclusion criteria included randomised clinical trials and crossover trials (level of evidence I), published within the last 10 years, involving adults with a diagnosis of rheumatoid arthritis, with no restrictions on gender, race, or ethnicity. All studies that addressed the use of foot orthoses and/or shoe therapy in any type of comparison between these interventions were considered relevant. Review Manager was used to carry out the bias analysis of the selected studies. The reporting was based on the new PRISMA guidelines. A total of 9 relevant articles were selected from an initial sample of 438. These articles analyse and compare the effectiveness of various types of foot orthoses in reducing pain, functional limitation, and disability, as well as improving balance and kinetic and kinematic parameters affected by rheumatoid arthritis. Foot orthoses reduce pain and disability in rheumatoid arthritis, improving balance and kinematic parameters. However, no significant improvements in the patients' functionality and walking ability have been demonstrated. Customised ones with good arch control, heel reinforcement, and metatarsal pad are more effective. No results on the impact of footwear on patients with rheumatoid arthritis have been found in the last 10 years. This systematic review was registered in PROSPERO (CRD42023405645).

Contribution of inflammation markers and quantitative sensory testing (QST) indices of central sensitisation to rheumatoid arthritis pain.

Pain, the primary complaint in rheumatoid arthritis (RA), is multifaceted, and may be driven by inflammatory disease activity and central sensitisation. We aimed to ascertain what proportion of RA pain severity is explained by markers of inflammation and quantitative sensory testing (QST) indices of central sensitisation. This was a cross-sectional analysis of data from individuals with clinically active RA. Pain severity was assessed using numerical rating scales and inflammation via 28-joint Disease Activity Score (DAS28) and Ultrasound (Greyscale, Power Doppler). Pain sensitivity was assessed by 'static' (tibialis anterior or brachioradialis pressure pain detection threshold-PPT-TA/PPT-BR) and 'dynamic' (temporal summation-TS, conditioned pain modulation-CPM) QST. Bivariate associations used Spearman's correlation coefficients, and multivariable linear regression models determined relative contributions to pain severity. In bivariate analyses of N = 96 (age 65 ± 10y, 77% females) people with RA, pain severity was significantly associated with inflammation indices (r = 0.20 to 0.55), and CPM (r=-0.26). In multivariable models that included TS, CPM, age, sex, and body mass index, inflammation indices remained significantly associated with pain severity. Multivariable models explained 22 to 27% of pain variance. Heterogeneity was apparent for associations with pain between subscores for pain now, strongest or average over the past 4-weeks. In individuals with clinically active RA, markers of inflammatory disease activity best explain RA pain with only marginal contributions from QST indices of central sensitisation. Although inflammation plays a key role in the experience of RA pain, the greater proportion of pain severity remains unexplained by DAS28 and ultrasound indices of inflammation.

Progression of TMJ disorders in patients with rheumatoid arthritis

Relevance. The literature highlights the significant impact of rheumatoid arthritis (RA) on the onset of musculoskeletal dysfunction symptoms in the temporomandibular joint (TMJ). However, the risk factors that influence the clinical manifestations of TMJ disorders in RA patients remain insufficiently explored.Objective: To examine the impact of rheumatoid arthritis on the onset and progression of TMJ disorders.Materials and methods. At the Dental Clinic of the Central Research Institute of Stomatology and Maxillofacial Surgery, 180 patients from St. Petersburg State Clinical Rheumatology Hospital No. 25, diagnosed with rheumatoid arthritis, were examined. Standard clinical assessments and detailed medical history collection were performed.Results. Patients with long-standing RA (over 5 years) were more likely to experience TMJ disorder symptoms, with a relative risk of 1.342 (95% CI) [1.106; 1.628]. No statistically significant correlation was found between RA activity and TMJ disorders. The symptom pattern varied by timing: prior to RA, patients predominantly experienced TMJ clicking and crepitus (66%); during RA onset, pain and restricted jaw movement were more common (80% and 72%, respectively). After RA manifestation, pain became the dominant symptom, though its intensity diminished over time (to 60%).Conclusions. The duration of RA has a notable impact on both the frequency and nature of TMJ disorder symptoms. While RA treatment reduces symptom intensity over time, their frequency remains high.

Olokizumab effect on chronic pain in rheumatoid arthritis: Results of the PROLOGUE observational study.

Evaluate the efficacy and safety ® (olokizumab) in patients with rheumatoid arthritis (RA) in real-world clinical practice, with a targeted assessment of patient report outcomes (PRO) and central sensitization. An open-label observational non-interventional study was conducted, enrolling 183 patients with moderate and severe RA activity. All patients received OKZ 64 mg SC as injections every 4 weeks (Q4W) with methotrexate. The patients' follow-up period was 24 weeks or less. RA activity (DAS28-CRP), pain severity (NRS), patient global assessment (PGA, NRS), functional impairment (NRS), fatigue (FACIT-F), central sensitization (central sensitization inventory, CSI), and symptoms of neuropathic pain (PainDETECT) were evaluated. The study cohort was comprised of 144 patients. And 39 patients were lost to follow-up, refused OKZ treatment, or were not dosed with OKZ for administrative reasons. In 6 months, DAS28-CRP decreased to 3.3 ± 0.9 (p < .001) and statistically significant reductions in pain intensity, PGA, functional impairment, and fatigue were achieved. Pain intensity decreased as early as 2 days after the first OKZ administration (p < .05). The number of patients with CSI >40 in 24 weeks decreased from 71.0% to 21.0% (p < .001), with PainDETECT >18 - from 21.5% to 13.2%. NSAIDs use decreased from 70.8% to 33.8% (р < .001), steroids - from 54.2% to 32.6%. AEs were reported in 14.2% patients, serious events were observed in three patients. OKZ is effective in reducing RA activity and controlling chronic pain related to dysfunction of the nociceptive system.

Predictors for severe persisting pain in rheumatoid arthritis are associated with pain origin and appraisal of pain

ObjectivesTo determine the proportion of patients with rheumatoid arthritis (RA) with severe persisting pain and to identify predictive factors despite treatment-controlled disease activity.MethodsThis prospective multicentre study included outpatients with RA...

Socioeconomic status, reserve capacity, and depressive symptoms predict pain in Rheumatoid Arthritis: an examination of the reserve capacity model

BackgroundGuided by the reserve capacity model, we evaluated the unique relationships between socioeconomic status (SES), reserve capacity (helplessness, self-efficacy, social support), and negative emotions on pain in patients with Rheumatoid Arthritis (RA).MethodsThe secondary analysis used baseline, cross-sectional data from 106 adults in a clinical trial comparing behavioral treatments for RA. Patients were eligible if they were ≥ 18 years old, met the ACR criteria for RA (determined by study rheumatologist), had stable disease and drug regimens for 3 months, and did not have a significant comorbid condition. Structural equation modeling evaluated the direct effects of SES, reserve capacity (helplessness- Arthritis Helplessness Index, self-efficacy -Personal Mastery Scale, social support- Social Provisions Scale) and negative emotions (stress and depressive symptoms- Perceived Stress Scale and Hamilton Depression Rating Scale) on pain (Rapid Assessment of Disease Activity in Rheumatology-RADAR & visual analog scale-VAS), and the indirect effects of SES as mediated by reserve capacity and negative emotions. The SEM model was evaluated using multiple fit criteria: χ2 goodness-of-fit statistic, the comparative fit index (CFI), the standardized root mean square residual (SRMR), and the root mean square error of approximation (RMSEA).ResultsParticipants were mostly female (85%), 55.45 years old on average, self-identified as white (61%), Hispanic (16%), black (13%), and other (10%), and had RA for an average of 10.63 years. Results showed that low SES contributed to worse pain, through lower reserve capacity and higher negative emotions. Mediational analyses showed that reserve capacity and negative emotions partially mediated the effect of SES on pain. The final model explained 39% of the variance in pain.ConclusionsThe findings indicate that lower SES was related to worse clinical pain outcomes and negative emotions and reserve capacity (helplessness, social support, and self-efficacy) mediated the effect of SES on pain. A primary limitation is the small sample size; future studies should evaluate this model further in larger, longitudinal approaches. Interventions that target negative emotions in patients with low SES may facilitate better pain control with RA.Trial registrationclinicaltrials.gov NCT00072657 01/02/2004 20/03/2009.

Theory of Biomechanical Evolution of the Rheumatoid Foot: A Narrative Review.

In patients with rheumatoid arthritis (RA), the pathological progression of lower limb biomechanics is established. Although specific aspects of RA gait patterns have been studied and described, we are aware of no studies of gait pattern compensations over the entire disease course. This study aimed to describe a model that could predict the evolution of lower limb pathomechanics in patients with RA. A literature review was conducted of electronic databases (MEDLINE, PEDro, Trip Database, DOAJ, BioMed Central, PLOS clinical trial, ScienceDirect, and CRD York University, AHRQ, NICE, Cochrane Library) to October 3, 2023. A theory was developed that all people with RA induce or augment gait evolution syndromes following the same biomechanical course. Specifically, we postulate the "rheumatoid equinus syndrome," the "rheumatoid abnormal pronation syndrome" and the "rheumatoid shuffle syndrome," which have never been described before. A new model of the evolution of gait compensation in RA is proposed. An important challenge of RA is that it increases the risk of ulcerative lesions, falls, pain, fractures, and healthcare costs. The proposed model can be used to reduce morbidity in this patient group by helping to explain and reduce the pain, deformity, and ankylosis of foot RA.

Exercise Training for Chronic Pain: Available Evidence, Current Recommendations, and Potential Mechanisms.

Chronic pain conditions pose a significant global burden of disability, with epidemiological data indicating a rising incidence. Exercise training is commonly recommended as a standalone or complementary approach for managing various chronic pain conditions like low back pain, osteoarthritis, rheumatoid arthritis, fibromyalgia syndrome, and neuropathic pain. Regardless of the specific condition or underlying cause (e.g., autoimmune disease, chronic inflammation), exercise training consistently leads to moderate to large reductions in pain. Moreover, exercise yields numerous benefits beyond pain alleviation, including small-to-moderate improvements in disability, quality of life, and physical function. Despite its efficacy, there is a lack of comprehensive research delineating the optimal intensity, duration, and type of exercise for maximal benefits; however, evidence suggests that sustained engagement in regular exercise or physical activity is necessary to achieve and maintain reductions in both clinical pain intensity ratings and the level that pain interferes with activities of daily living. Additionally, the precise mechanisms through which exercise mitigates pain remain poorly understood and likely vary based on the pathophysiological mechanisms underlying each condition.

How to Distinguish Non-Inflammatory from Inflammatory Pain in RA?

Managing non-inflammatory pain in rheumatoid arthritis (RA) can be a huge burden for the rheumatologist. Pain that persists despite optimal RA treatment is extremely challenging for patient and physician alike. Here, we outline the latest research relevant to distinguishing non-inflammatory from inflammatory RA pain and review the current understanding of its neurobiology and management. Nociplastic pain is a recently introduced term by the international pain community. Its definition encompasses the non-inflammatory pain of RA and describes pain that is not driven by inflamed joints or compromised nerves, but that is instead driven by a functional reorganisation of the central nervous system (CNS). Insights from all areas of nociplastic pain research, including fibromyalgia, support a personalised pain management approach for non-inflammatory pain of RA, with evidence-based guidelines favouring use of non-pharmacological interventions. Future developments include novel CNS targeting pharmacotherapeutic approaches to treat nociplastic pain.

Adjunct role of potassium-rich vegetarian diet and a novel potassium food supplement to improve pain in chronic rheumatoid arthritis on supervised standard care: a randomised controlled study

IntroductionAn earlier food survey showed dietary potassium deficiency in rheumatoid arthritis (RA).ObjectiveTo evaluate an adjunct role of oral potassium to reduce joint pain in RA.Methods172 consenting eligible symptomatic patients (median...

Application of Foot Massage Therapy to Reduce Pain Scale of Old Age with Rheumatoid Arthritis in Perumnas Public Health Center Working Area Lubuklinggau City 2023

Arthritis in RA patients causes pain, swelling, and decreased joint range of motion. It can lead to decreased independence and limited activities, reducing the quality of life. The process of foot massage also impacts the process of vasodilation and increased blood circulation. It increases the activity of the autonomic nervous system, which stimulates increased production of endorphins, which is expected to reduce pain. The case study used a descriptive method with two old older adults with Rheumatoid Arthritis, using the family nursing care assessment and pain scale assessment. The application of foot messages is carried out for 20 minutes for three days. After applying foot massage for three consecutive days, the study showed a decrease in pain intensity between before and after the intervention was given to the two subjects. The subject's pain intensity decreased from moderate pain intensity to mild pain. Applying foot massage effectively reduces the intensity of Rheumatoid Arthritis pain.

Relation Between Fast Food and Preservative Consumption with Rheumatoid Arthritis Pain in A Gymnastics Group in Bandung City

Background: Rheumatoid arthritis is an autoimmune disease in the form of joint inflammation in adults. Based on the 2018 WHO report, it shows that there are 335 million people in the world who have rheumatism, of which 5-10% are aged 5-20 years and 20% are aged 55 years. Factors that can cause pain in rheumatoid arthritis are dietary factors, one of which is frequent consumption of fast food and preserved foods. The aim of this study was to determine the relationship of consumption of fast food and preserved foods to rheumatoid arthritis complaints in two gymnastics groups in Bandung City.Methods: This study used a cross-sectional design with a sample of 30 gymnastic ladies taken by purposive sampling. Data were analyzed using the Chi-Square test with IBM SPSS Statistic 21 software.Results: Based on the results of the analysis that has been done, there is no relationship between age, educational history, consumption of fast food and preserved food with rheumatoid arthritis complaints in the group of gymnastics ladies in Bandung City (p0,05).Conclusions: The absence of an association among age, educational history, consumption of fast food and preserved foods with rheumatoid arthritis complaints can be due to other factors outside of these factors such as genetics, gender, obesity, infectious diseases, and lack of knowledge about rheumatoid arthritis. What's more, rheumatoid arthritis is also a multifactorial disease, so we need to wisely maintain and regulate his, her, their, etc lifestyle and food intake so that rheumatoid arthritis complaints can be minimized and do not have recurrences.

Intense symptoms of pain are associated with poor sleep, fibromyalgia, depression and sleep apnea in patients with rheumatoid arthritis and psoriatic arthritis. A register-based study

ObjectivesTo study whether poor sleep and comorbidities are associated with high symptom levels of patient-reported outcomes (PROs) pain, patient global assessment and fatigue in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in a nation-wide cross-sectional setting. MethodsClinical data were extracted from The Finnish Rheumatology Quality Register between 1.2021 and 9.2022. Self-reported sleep was categorized as “good” (little/no difficulties) or “poor” (great difficulties/can’t) sleep. Data concerning comorbidities were collected from national registers. Descriptive statistics were used. Regression analyses were applied to analyze independent associations of sleep status, comorbidities and disease activity with pain in RA and PsA, adjusting for age and sex. ResultsAmong 13,512 patients with RA, 6052 [mean (SD) age 62 (13), 71% female] had sleep status reported; in PsA 1861/3636 [age 55 (13), 48% female]. In RA, 5072 (84%) reported good and 980 (16%) poor sleep; the corresponding numbers in PsA were 1460 (78%) and 401 (22%). Median values for objective disease activity were low and similar in patients with poor sleep and good sleep in both diseases. Among patients with no swollen joints, the median values for PROs were approximately three times higher for patients with poor sleep vs. good sleep in both diagnoses (P<0.001). In regression analyses, “poor” sleep was independently associated with higher symptoms in pain [B (95%CI) 20 (18,22) in RA and 23 (19, 26) in PsA], followed by comorbid fibromyalgia, as well as depression in RA and sleep apnea in PsA. Conclusion“Poor” sleep quality and comorbidities are independently associated with pain. Patient's sleep status is important to know especially in patients with severe symptoms without objective disease activity.

Assessing the effects of distinct biologic therapies on rheumatoid arthritis pain by nociceptive, neuropathic and nociplastic pain components: a randomised feasibility study

BackgroundPain management is a major unmet need in people with rheumatoid arthritis (RA). Although many patients are treated with disease modifying anti-rheumatic drugs (DMARDS), including biologic therapies, many people with RA continue to experience significant pain. We aimed to determine whether performing a comprehensive pain evaluation is feasible in people with active RA receiving conventional DMARDs and biologic therapies.MethodsThe BIORA-PAIN feasibility study was an open-label, randomised trial, which recruited participants suitable for treatment with biologic therapy. The primary feasibility outcomes were recruitment, randomisation and retention of eligible participants. All participants underwent pain assessment for nociceptive, neuropathic and nociplastic pain during the 12-month study period, with quarterly assessments for VAS (Visual Analogue Scale) pain, painDETECT and QST (quantitative sensory testing). This trial was registered in clinicaltrials.gov NCT04255134.ResultsDuring the study period, 93 participants were screened of whom 25 were eligible: 13 were randomised to adalimumab and 12 to abatacept. Participant recruitment was lower than expected due to the COVID-19 pandemic. Pain assessments were practical in the clinical trial setting. An improvement was observed for VAS pain from baseline over 12 months, with a mean (SEM) of 3.7 (0.82) in the abatacept group and 2.3 (1.1) in the adalimumab group. There was a reduction in painDETECT and improvement in QST measures in both treatment groups during the study. Participant feedback included that some of the questionnaire-based pain assessments were lengthy and overlapped in their content. Adverse events were similar in both groups. There was one death due to COVID-19.ConclusionsThis first-ever feasibility study of a randomised controlled trial assessing distinct modalities of pain in RA met its progression criteria. This study demonstrates that it is feasible to recruit and assess participants with active RA for specific modalities of pain, including nociceptive, neuropathic and nociplastic elements. Our data suggests that it is possible to stratify people for RA based on pain features. The differences in pain outcomes between abatacept and adalimumab treated groups warrant further investigation.Trial registrationNCT04255134, Registered on Feb 5, 2020.

Novel nano-in-micro fabrication technique of diclofenac nanoparticles loaded microneedle patches for localised and systemic drug delivery

Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly prescribed for managing osteoarthritis, rheumatoid arthritis, and post-surgical pain. However, oral administration of diclofenac often leads to adverse effects. This study introduces an innovative nano-in-micro approach to create diclofenac nanoparticle-loaded microneedle patches aimed at localised, sustained pain relief, circumventing the drawbacks of oral delivery. The nanoparticles were produced via wet-milling, achieving an average size of 200 nm, and then incorporated into microneedle patches. These patches showed improved skin penetration in ex vivo tests using Franz-cell setups compared to traditional diclofenac formulations. In vivo tests on rats revealed that the nanoparticle-loaded microneedle patches allowed for quick drug uptake and prolonged release, maintaining drug levels in tissues for up to 72 h. With a systemic bioavailability of 57 %, these patches prove to be an effective means of transdermal drug delivery. This study highlights the potential of this novel microneedle delivery system in enhancing the treatment of chronic pain with reduced systemic side effects.