Interstitial cystitis/bladder pain syndrome (IC/BPS) and fibromyalgia (FM) are chronic pain conditions frequently discussed within shared conceptual frameworks such as central sensitization. Despite this conceptual overlap, IC/BPS is clinically characterized by pelvic and urinary symptoms, whereas FM is associated with widespread pain, fatigue, sleep disturbance, and other systemic manifestations. Whether these differences are reflected in the organization of symptom-related language within patient-generated discourse remains insufficiently characterized. Patient-generated text related to IC/BPS and FM was collected from disease-specific Reddit communities using identical retrieval procedures, yielding temporally comparable corpora. A predefined evaluative lexicon was constructed from validated clinical questionnaires together with pain-related, affective, and anatomical vocabulary. Symptom-language co-occurrence networks were analyzed using a three-step framework examining global pain-centered network organization, dense-core topology and community structure, and local pain-centered lexical configurations. Both conditions exhibited pain-centered symptom-language networks. However, the FM network showed a greater concentration of symptom-language terms within the immediate network neighborhood of "pain," whereas the IC/BPS network retained a larger peripheral structure. Dense-core analysis revealed distinct topological organization. The IC/BPS dense core retained partial modular differentiation, whereas the FM dense core formed a highly interconnected structure with minimal residual community organization. At the local level, pain-centered lexical neighborhoods also differed between conditions. In IC/BPS, "pain" was preferentially associated with pelvic, urinary, and sensory terms, whereas in FM it was more frequently associated with whole-body, fatigue-, sleep-, chronicity-, and affect-related vocabulary. These findings indicate that two chronic pain conditions sharing substantial conceptual overlap nevertheless exhibit distinct pain-centered symptom-language topologies within patient-generated discourse. Comparative network analysis of patient-generated language may provide a complementary framework for characterizing disease-specific patterns of symptom-language organization in online health communities.

Intervertebral disc degeneration (IVDD) is a major contributor to chronic low back pain, yet its molecular mechanisms remain incompletely understood. Emerging evidence suggests that ferroptosis, an iron-dependent form of regulated cell death, may play a key role in the degeneration of nucleus pulposus cells (NPCs). However, its involvement in IVDD has not been systematically explored. Resveratrol (Res), a natural polyphenol with antioxidant and cytoprotective effects, shows therapeutic potential, but its regulatory role in ferroptosis during IVDD is unclear. In this study, bulk transcriptome analysis identified 22 ferroptosis-related differentially expressed genes, among which five hub genes (GPX4, FTH1, HMOX1, NCOA4, and TFRC) were strongly linked to ferroptosis and oxidative stress pathways. Single-cell transcriptome data further revealed dynamic expression of these genes in NP cells, showing decreased GPX4 and FTH1 and increased HMOX1, NCOA4, and TFRC along the differentiation trajectory. High-dimensional weighted gene co-expression network analysis (hdWGCNA) confirmed significant associations between ferroptosis-related gene modules and IVDD pathology. Validation using human clinical samples, NP cell models, and animal experiments demonstrated that Res alleviates IVDD by modulating hub gene expression and suppressing NP cell ferroptosis. Overall, this study highlights ferroptosis as a key mechanism driving IVDD and identifies resveratrol as a promising therapeutic candidate targeting NP cell ferroptosis.

Knee osteoarthritis is a leading cause of pain and disability and frequently results in total knee arthroplasty (TKA). Decisions about surgery and postoperative management rely largely on subjective pain scales and patient-reported outcome measures (PROMs), and 10-15% of patients remain dissatisfied after TKA despite technically successful surgery. Evidence suggests that pain is partly reflected in peripheral immune signalling, yet this neuroimmune interface has not been studied in patients with joint pain due to knee osteoarthritis. This study will explore whether peripheral immune responses (interleukin-1 beta, IL-1β) are associated with pain and may serve as objective pain biomarkers in patients with painful knee osteoarthritis compared with pain-free controls and how these markers relate to pain and psychological (anxiety, depression and pain catastrophising) PROMs. This will be the first study to correlate pain markers (peripheral immune responses) with subjective pain levels in orthopaedic patients with symptomatic knee osteoarthritis.

Neuropathic pain (NP) is a complex and debilitating condition characterized by persistent pain due to nerve injury, underscoring the urgent need for improved diagnostic and treatment strategies. Although the glycogen metabolic process (GMP) has been reported to play an important role in NP pathology, the underlying mechanisms remain unclear. We conducted a bioinformatic analysis of transcriptomic datasets of patients with NP in the GEO database and identified three GMP-related hub genes (STK40, PRKAG2, and PHKA1) with strong combined diagnostic potential, achieving an area under the curve (AUC) of 0.832. Subsequent experiments demonstrated that after chronic constriction injury (CCI), only STK40 was significantly upregulated in macrophages of the dorsal root ganglia (DRG). Microinjection-mediated silencing of STK40 in the DRG or conditional knockout of STK40 in DRG macrophages alleviated pain-related behaviors in CCI mice. Mechanistically, STK40 promotes macrophage inflammatory responses by inhibiting the conversion of UDP-glucose (UDPG) to glycogen through the AKT/GSK3β/GYS1 signaling axis. These findings reinforce the importance of GMP in NP and identify STK40 as a potential therapeutic target for NP.

Co-design is increasingly used in chronic pain research; however, terminology remains inconsistent, guidance is lacking, and most research is concentrated in high-income countries. This international three-round e-Delphi study aimed to establish consensus on key terminology and core components, and to identify common barriers and strategies for co-design in chronic pain management. The e-Delphi survey was conducted from November 2024 to June 2025. Panel used a five-point Likert scale to rate agreement and importance, with consensus defined 75% thresh-hlod agreement. Open-ended responses on barriers and strategies were analysed using thematic content analysis. A total of 117 panel members participated in Round 1, 98 in Round 2, and 92 in Round 3, representing 30 countries. Though panel members prioritise "co-design" and "collaborative design" as the most appropriate standardised terms to describe the collaboration process in developing and evaluating chronic pain interventions, "co-design" has the highest percentage agreement. Twelve core components of co-designed interventions were identified, including engaging people with lived experience and key interest-holders, addressing biopsychosocial factors, ensuring accessibility and availability, applying evidence-based practices, emphasising person-centredness, conducting needs assessments, supporting goal-oriented care, empowering self-management, promoting interdisciplinary collaboration, ensuring sustainability, incorporating patient-reported outcome measures, and integrating technology. The identified five barriers to co-design were: resource, cultural and contextual; knowledge and educational; interpersonal and professional; and system and policy. Corresponding strategies included enhanced resource allocation, training and education, improved communication, strengthened interdisciplinary collaboration, and supportive policy and organisational structures. These findings provide a clear, consensus-based guide for developing and implementing co-designed chronic pain interventions. PERSPECTIVE: This e-Delphi study established standardised terminology, core components for co-designed chronic pain intervention development, and outlined key barriers and overcoming strategies for them. The findings could enhance research and clinical communication and support embedding co-design principles into clinical service development to improve shared decision-making and patient-centred care.

Inferior vena cava thrombosis (IVCT) is an uncommon manifestation of venous thromboembolism, characterized by heterogeneous clinical presentation and limited disease-specific evidence. Owing to its rarity, diagnostic and therapeutic strategies are largely extrapolated from studies in proximal lower-limb deep vein thrombosis, resulting in substantial variability in clinical practice. This guidance document, developed by the Italian Society for the Study of Haemostasis and Thrombosis (SISET), aims to provide pragmatic, evidence-informed recommendations for the identification, diagnosis, thrombophilia work-up, and management of IVCT. The guidance is based on a structured review of the available literature and expert consensus. The document addresses key clinical questions, including which patients should be investigated for IVCT, the most appropriate diagnostic imaging strategies, indications for thrombophilia testing, and optimal pharmacological and interventional management. Particular attention is given to clinical scenarios that should prompt dedicated evaluation of the inferior vena cava, such as bilateral lower-extremity deep vein thrombosis, atypical abdominal or lumbar pain, and extensive venous obstruction. Anticoagulation is recommended as the cornerstone of IVCT treatment, while endovascular or surgical interventions should be reserved for selected patients with acute extensive thrombosis or chronic symptomatic ilio-caval obstruction. Given the paucity of high-quality, IVCT-specific evidence, these recommendations emphasize individualized decision-making and highlight the need for prospective studies in this field.

Enteropathic spondyloarthritis is a common, under-recognised musculoskeletal manifestation of inflammatory bowel disease and a potentially preventable contributor to long-term disability. Epidemiological, imaging, and biomarker data support a continuum from at-risk states (ie, high-risk inflammatory bowel disease phenotypes with early extraintestinal manifestations and non-specific pain), through subclinical MRI-defined or ultrasound-defined sacroiliac and entheseal inflammation, to early clinical enteropathic spondyloarthritis with overt synovitis, enthesitis, and inflammatory back pain, often after prolonged diagnostically ambiguous symptoms. This transition unfolds within a gut-derived inflammatory milieu shaped by type-3 immunity, dysbiosis, epithelial barrier dysfunction, gut-homing and tissue-resident lymphocyte circuits, and polygenic susceptibility, with only partial synchrony between intestinal and musculoskeletal trajectories. Clinically, these mechanisms yield phase-specific signatures in which faecal calprotectin, C-reactive protein, and HLA-B27 act as probabilistic modifiers, and power Doppler ultrasound and sacroiliac or spinal MRI enable recognition of inflammation before irreversible structural change. In this Review, we synthesise mechanistic and clinical evidence across the at-risk-to-early articular continuum (this term refers to individuals at-risk of enteropathic spondyloarthritis, individuals with subclinical musculoskeletal disease, and patients with early clinical articular disease). We propose a precision, dual-compartment strategy addressing both gut and joint involvement, integrating structured musculoskeletal screening, probability-guided imaging, and timely use of therapies with proven gut-joint efficacy into inflammatory bowel disease care, aiming to prevent diagnostic delay, limit structural damage, and reframe enteropathic spondyloarthritis as an interceptable, treat-to-target phenotype along the gut-joint axis.

Objective
Deep brain stimulation (DBS) for neuropsychiatric disorders increasingly relies on patient personalized approaches. One strategy to identify viable targets for personalized stimulation and biomarker detection uses a temporary, inpatient stereoelectroencephalography (sEEG) trial to identify optimal targets for permanent re-implantation. However, this approach reasons that neural signals are stable between repeated intracranial electrode implants, which is not yet validated.

Approach
We characterize the spectral stability of local field potentials after electrode reimplantation from an ongoing single-center clinical trial using two-staged sEEG/DBS for chronic pain (NCT04144972).

Main Results
Repeat neurosurgical implant of intracranial electrodes reliably targeted intended trajectories across staged surgeries occurring months apart (2.1 ± 1.2 mm Euclidean distance across 17 brain targets, 5 participants). Anatomical targeting error was correlated with differences in recorded electrophysiological power spectra between stages (r(15) = 0.51, p = 0.03). This correlation was stronger for the subset of regions re-targeted exclusively for biomarker sensing (r(6) = 0.73, p = 0.04), and non-significant for therapeutic stimulation sites (r(7) = .23, p = 0.76). Similarly, a multiple regression model significantly predicted spectral distance (F(4, 13) = 5.99, p = 0.008, adjusted r = 0.70) with an interaction between electrode type and Euclidean distance (t (13)= 2.39, p = 0.03).

Significance
Chronic intracranial EEG signals recapitulated temporary recordings in 17 of 17 brain regions with the major spectral peak within 1 Hz. Our results demonstrate the temporal stability of neural signals across months and validate the use of a two-staged intracranial EEG approach for chronic DBS sensing in humans.

Autoimmune pericarditis is commonly idiopathic but may represent the initial manifestation of systemic autoimmune disease. Hepatic autoimmune disorders rarely present with primary cardiac involvement, and recognition of extrahepatic presentations is essential for early diagnosis and prevention of organ damage. Autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome is an uncommon entity characterized by combined hepatocellular and cholestatic immune-mediated injury. A previously healthy young woman presented with progressive pleuritic chest pain and dyspnea and was found to have a large pericardial effusion causing hemodynamic compromise requiring surgical drainage. Pericardial pathology demonstrated acute and chronic fibrinous pericarditis. Initial evaluation revealed elevated inflammatory markers and mild transaminitis with positive autoimmune serologies including antinuclear antibody and anti-smooth muscle antibody. Following clinical improvement, she developed recurrent pericarditis accompanied by worsening liver enzyme abnormalities. Liver biopsy demonstrated chronic active hepatitis with bile duct injury and bridging fibrosis, consistent with autoimmune hepatitis-primary biliary cholangitis overlap syndrome. Cardiac magnetic resonance imaging confirmed active pericardial inflammation without myocarditis. Immunosuppressive therapy with corticosteroids followed by azathioprine resulted in clinical stabilization. This case highlights autoimmune pericarditis as the presenting manifestation of AIH-PBC overlap syndrome and underscores the importance of evaluating unexplained pericarditis for systemic autoimmune disease. Early recognition of cardio-hepatic autoimmune overlap allows timely immunosuppressive therapy and may prevent progression to advanced hepatic fibrosis.

Chronic pain is notoriously complex to manage and treat. In this News and Perspectives article, JMIR Correspondent Vanessa Nirode reports on several digital innovations that may help to bridge existing care gaps.