The complexity of pain in inflammatory arthropathies beyond pain intensity and impact: An OMERACT initiative.

Introduction Pain in both peripheral and axial joints is a major symptom in patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). Emerging evidence demonstrates pain mechanisms, beyond those related to inflammation or joint damage, based on aberrant processing of nociceptive stimuli peripherally as well as centrally. The Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway has been implicated in the processing of pain beyond its role in mediating inflammation and inhibitors of this pathway approved for the treatment of axSpA and PsA have been shown to alleviate a broad array of pain outcomes in both axial and peripheral joints. Areas covered We review recent definitions and standardization of the nomenclature for categorizing chronic pain according to causality, assessment tools to evaluate nociplastic pain, the pathophysiologic role of JAK-STAT signaling in nociplastic pain, evidence for the presence of nociplastic pain in axSpA and PsA, and the impact of JAK inhibitors (JAKi) on pain outcomes in clinical trials (PubMed: 01/01/2019-04/01-2024). Expert opinion Nociplastic pain assessment has been confined almost entirely to the use of a limited number of questionnaires in cross-sectional studies of these diseases. Though effective for alleviating pain, it is unclear if JAKi specifically impact nociplastic pain.

Nociplastic pain is a mechanistic term used to describe pain that arises or is sustained by altered nociception, despite the absence of tissue damage. Although nociplastic pain has distinct pathophysiology from nociceptive and neuropathic pain, these pain mechanisms often coincide within individuals, which contributes to the intractability of chronic pain. Key symptoms of nociplastic pain include pain in multiple body regions, fatigue, sleep disturbances, cognitive dysfunction, depression and anxiety. Individuals with nociplastic pain are often diffusely tender - indicative of hyperalgesia and/or allodynia - and are often more sensitive than othersto non-painful sensory stimuli such as lights, odours and noises. This Review summarizes the risk factors, clinical presentation and treatment of nociplastic pain, and describes how alterations in brain function and structure, immune processing and peripheral factors might contribute to the nociplastic pain phenotype. This article concludes with a discussion of two proposed subtypes of nociplastic pain that reflect distinct neurobiological features and treatment responsivity.

BackgroundThe newly proposed low back pain treatment requires case classification according to the pain mechanism (nociceptive, neuropathic or nociplastic) to determine the most effective therapeutic approach. However, there is a lack of objective tools for distinguishing these pain mechanisms. The aim of the study was to identify which symptoms, signs, and standard diagnostic parameters would allow predicting the nociplastic pain (NP) subtype among low back leg pain (LBLP) patients.MethodsA retrospective analysis of an LBLP case–control study database was carried out. The presence of NP was assumed if the patient presented with myofascial pain syndrome (MPS) and developed a short-term intensive vasodilatation reaction in the perceived lower leg pain area after provocation by a minimally invasive procedure. Clinical data and standard LBLP diagnostic parameters were analyzed to classify patients as NP (+) vs NP (-). Next, to predict NP probability, logistic regression analysis and a diagnostic classification tree were constructed.ResultsNP was confirmed in 43.75% of LBLP patients. Women represented 95.24% of all NP (+) patients. The diagnostic classification tree indicated that NP was highly probable if the LBLP subject was female and the result of a positive straight leg raise (SLR) test was lower than 45 degrees. If the SLR test result was greater than or equal to 45 degrees, a negative result on the Bragard test would have diagnostic value. This classification tree was approved to a certain extent in the logistic regression model (deviance residuals, min: −1.8519; 1Q: −0.5551; median: −0.1907; 3Q: 0.6565 and max: 2.1058) but should be verified in a larger group of subjects.ConclusionFemale sex, but not clinical data or standard diagnostic parameters, is indicative of nociplastic pain in LBLP patients. More sophisticated statistical methods, based on directly measurable parameters, should be proposed to distinguish NP involvement in LBLP.

BackgroundPain represents one of the main clinical symptoms of Rheumatoid Arthritis (RA) being used as an indicator of disease activity. However, many RA patients reports clinically significant levels of pain...

The purpose — to determine clinical and laboratory features of axial psoriatic arthritis (AxPsA); to study the impact of nociplastic pain (NP) on the clinical features and quality of life (QoL) in patients with AxPsA. Material and methods. 127 adult patients with psoriatic arthritis (PsA) were included. The number of tender (TJ) and swollen joints (SJ), patient global assessment and severity of pain, C-reactive protein (CRP) were determined. Activity of PsA was assessed with DAPSA, ASDAS, and BASDAI. NP was determined by screening using the CSI and neurologist’s examination. Sacroiliitis (SI) was determined with MRI. QoL was assessed with PsAID-12 and ASAS-HI. Results. SI was found in 60 (47.2%) patients with PsA (AxPsA). The TJ, SJ, CRP, DAPSA, ASDAS were found in higher values and values of CRP above normal, erosive peripheral arthritis and enthesitis were more often found in patients with AxPsA. NP was found in 30 (50%) patients with AxPsA who showed worse pain scores, BASDAI, ASDAS, and QoL. The indicators of TJ, SJ, and CRP in the groups did not differ. Conclusion. SI in PsA is associated with more severe peripheral and laboratory manifestations, but not with more severe pain. Patients with AxPsA with NP have higher rates of disease activity which are associated with degradation of patient reported outcomes including QoL without degradation of inflammation signs. For improving the QoL of patients with PsA it is necessary to study the mechanisms of chronic pain.

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At the intersection of anger, chronic pain, and the brain: A mini-review

Aims and Scopes

Background:Multiple mechanisms underly the major burden of rheumatoid arthritis (RA) pain. The high prevalence of co-existing fibromyalgia (FM) supports the contribution of central nervous system associated nociplastic pain pathways. In...

Background: Many pain-clinic patients have chronic musculoskeletal pain that is disproportionate to imaging and examination, poorly responsive to interventions, and accompanied by fatigue, sleep disturbance, and other central symptoms. The International Association for the Study of Pain introduced nociplastic pain as a third mechanistic descriptor, alongside nociceptive and neuropathic pain. Objective: This study aimed to summarize concepts and mechanisms of nociplastic pain relevant to pain physicians and propose a concise, clinic-friendly Daradia Nociplastic Pain Checklist to support bedside identification and management. Materials and Methods: This narrative review synthesizes contemporary literature on nociplastic pain, central sensitization, and clinical criteria, together with clinical experience from a specialized pain center. Based on this, we developed a pragmatic 10-item checklist with a simple scoring algorithm for outpatient and interventional settings. Results: Nociplastic pain arises from altered nociception and central sensitization, typically presenting with disproportionate, often widespread pain, central symptom, limited response to interventions, and no nociceptive or neuropathic lesion. The Daradia checklist includes items on chronicity, disproportion, pain distribution, sensory findings, central symptoms, history of central sensitivity syndromes, response to peripheral treatments, and absence of dominant nociceptive or neuropathic drivers. A positive response to ≥3 items suggests suspected nociplastic pain; ≥7 items, in the absence of a clear alternative explanation, support nociplastic-dominant pain. Management is organized around three pillars: EXPLAIN (education), MOVE (graded activity), and CALM (sleep, mood, stress, and rational pharmacotherapy). Conclusion: Systematic use of this checklist and the 3/7 rule may help integrate nociplastic reasoning into routine practice, reduce low-value interventions, and support mechanism-based multimodal care.

Fibromyalgia syndrome (FMS) is a complex condition characterized by numerous symptoms, especially long-lasting widespread pain. Available evidence suggests that the main causes of FMS are nociplastic pain mechanisms, but nociceptive and neuropathic pain components can also be involved, which would in these cases characterize FMS as a mixed-pain condition. In 2021, a comprehensive set of clinical criteria and grading systems was developed in accordance with the International Association for the Study of Pain. The establishment of these criteria is an important step toward precision pain medicine, with great potential for the assessment and treatment of FMS. The aim of this study was to develop clinical recommendations for pain phenotyping, including the phenotyping of mixed pain, in patients with FMS. Narrative review. Within this framework, an international and multidisciplinary group of pain specialists have developed clinical recommendations for integrating a mixed pain phenotype into the current framework of phenotyping FMS. A modified nominal group technique was used to develop the consensus recommendations. A manual is provided to allow clinicians to differentiate between predominant nociplastic pain and mixed pain when phenotyping FMS patients. A 7-step diagnostic approach, performed in 2 parts, is presented and illustrated using 3 case examples to enhance understanding and encourage effective implementation of this approach in research settings and clinical practice. Studies examining the clinometric properties of these recommendations and this grading system for mixed pain in FMS are warranted. The current recommendations systematically summarize the methods that allow individuals with FMS to be classified into nociplastic or mixed pain phenotypes, based on potential nociceptive and neuropathic pain components.

BackgroundPain remains a principal complaint for people with psoriatic arthritis (PsA), despite successful mitigation of inflammation. This situation alludes to the co-existence of distinct pain mechanisms. Nociceptive and nociplastic mechanisms are clinically challenging to distinguish. Advances in brain functional magnetic resonance imaging (fMRI) have successfully characterised distinct pain mechanisms across several disorders, in particular implicating the insula. This is the first study to characterise neurobiological markers of pain mechanisms in PsA employing fMRI.MethodsPsA participants underwent a 6-minutes resting-state fMRI brain scan, and questionnaire assessments of nociplastic pain (2011 ACR fibromyalgia criteria) and body pain, assessed using the Numeric Rating Scale (NRS, 0-100). Functional connectivity between insula seeds (anterior, mid, posterior), and the whole brain was correlated with the above pain outcomes correcting for age and sex, and false discovery rate (FDR) for multiple comparisons.ResultsA total of 46 participants were included (age 49 ± 11.2; 52% female; FM score 12.5 ± 5.7; overall pain 34.8 ± 23.5). PsA participants with higher fibromyalgia scores displayed increased connectivity between: (1) right anterior insula to DMN (P < 0.05), (2) right mid and left posterior insula to parahippocampal gyri (P < 0.01 FDR); and (3) right mid insula to left frontal pole (P = 0.001 FDR). Overall pain was correlated with connectivity of left posterior insula to classical nociceptive regions, including thalamus (P = 0.01 FDR) and brainstem (P = 0.002 FDR).ConclusionFor the first time, we demonstrate objectively that nociceptive and nociplastic pain mechanisms co-exist in PsA. PsA pain cannot be assumed to be only nociceptive in origin and screening for nociplastic pain in the future will inform supplementary analgesic approaches.

Nine patient research partners (PRPs) attended the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting in person in Dublin, Ireland. The importance of close relations between researchers, clinicians, and PRPs was highlighted at the PRP premeeting, with discussion regarding PRP engagement within GRAPPA with the GRAPPA leadership team. A presentation was given by PRPs at the plenary session, and there was continued active engagement of PRPs in breakout sessions, workshops, and plenary sessions compared to previous annual meetings. The GRAPPA PRP Network is committed to supporting the GRAPPA mission and contributing the unique perspectives of dedicated, knowledgeable individuals with the lived experience of psoriatic disease. This report provides a summary of the GRAPPA PRP Network meetings at the GRAPPA 2023 annual meeting and the continued commitment of the GRAPPA PRP Network to enhance PRP involvement within GRAPPA activities.

Pain is a significant issue in rheumatoid arthritis (RA) and psoriatic arthritis (PSA) and can have a negative impact on patients' quality of life. Despite optimal control of inflammatory disease, residual chronic pain remains a major unmet medical need in RA. Pain in RA can be secondary to inflammation but can also generate neuroendocrine responses that initiate neurogenic inflammation and enhance cytokine release, leading to persistent hyperalgesia. In addition to well-known cytokines such as TNFα and IL-6, other cytokines and the JAK-STAT pathway play a role in pain modulation and inflammation. The development of chronic pain in RA involves processes beyond inflammation or structural damage. Residual pain is often observed in patients even after achieving remission or low disease activity, suggesting the involvement of non-inflammatory and central sensitization mechanisms. Moreover, fibromyalgia syndrome (FMS) is prevalent in RA patients and may contribute to persistent pain. Factors such as depression, sleep disturbance, and pro-inflammatory cytokines may contribute to the development of fibromyalgia in RA. It is essential to identify and diagnose concomitant FMS in RA patients to better manage their symptoms. Further research is needed to unravel the complexities of pain in RA. Finally, recent studies have shown that JAK inhibitors effectively reduce residual pain in RA patients, suggesting pain-reducing effects independent of their anti-inflammatory properties.

Since 2003, patients have become increasingly involved in research endeavours related to psoriatic arthritis (PsA), progressing into a patient research partner (PRP) role. This paper reviews the general considerations related to PRP involvement in research endeavours and more specifically, the evolution of PRP contributions related to PsA research. The addition of the perspective from individuals with lived experience of PsA can bring unique insights to the research process, and increase the likelihood that the results of research are meaningful and relevant to PsA patients. There are also potential issues to address when incorporating PRPs, such as the need for additional time and effort to identify, train, and collaborate with PRPs as members of a research team. Overall, while there are challenges to overcome, and the opportunities to include PRPs are sometimes overlooked, efforts to include PRPs in PsA research should offer significant benefits to patients, researchers, and trials.