# The Association Between Neuropathic Pain, Pain Intensity, and Inflammatory Activity in Rheumatoid Arthritis

**Authors:** Zeynel Abidin Akar, Dilan Yıldırım, Ömer Karakoyun, Kadir Kaya, Mehmet Çağlayan, Pelin Oktayoğlu, Remzi Çevik

PMC · DOI: 10.3390/jcm15041601 · 2026-02-19

## TL;DR

This study finds that nociplastic-like pain features are common in rheumatoid arthritis and are linked more to pain intensity and psychosocial factors than to inflammation.

## Contribution

The study identifies independent predictors of nociplastic-like pain features in RA, highlighting non-inflammatory factors.

## Key findings

- Nociplastic-like pain features were present in 22.5% of RA patients.
- Pain intensity, fatigue, and sleep quality were strongly associated with these pain features.
- Inflammatory markers like CRP and ESR were not significant predictors of nociplastic-like pain features.

## Abstract

Background: Nociplastic-like pain features are increasingly recognized as significant contributors to chronic pain and reduced quality of life in patients with rheumatoid arthritis (RA). However, their clinical correlates and relationship with disease activity remain incompletely understood. Objective: To evaluate the prevalence of nociplastic-like pain features in patients with RA and to investigate their associations with disease activity, pain intensity, fatigue, sleep quality, and health-related quality of life. Methods: In this cross-sectional study, 160 patients with RA were enrolled. Nociplastic-like pain features were assessed using the PainDETECT questionnaire. Disease activity was evaluated using the Disease Activity Score in 28 joints (DAS28). Pain intensity, fatigue, sleep quality, and health-related quality of life were assessed using the visual analog scale (VAS), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), Pittsburgh Sleep Quality Index (PSQI), and Short Form-36 (SF-36), respectively. Continuous variables were compared using t-tests or Mann–Whitney U tests according to data distribution. Stepwise multivariate linear regression analysis was performed to identify independent factors associated with PainDETECT scores. Results: Pain patterns suggestive of nociplastic-like features were identified in 22.5% of patients. These patients had significantly higher pain intensity, greater fatigue (lower FACIT-F scores), poorer sleep quality (higher PSQI scores), and lower SF-36 scores across all domains compared with patients without these features (all p < 0.001). PainDETECT scores showed a strong positive correlation with VAS pain intensity (r = 0.679, p < 0.001) and a moderate correlation with DAS28 (r = 0.536, p < 0.001). PainDETECT scores were negatively correlated with FACIT-F (r = −0.512, p < 0.001) and several SF-36 domains. In stepwise multivariate regression analysis, pain intensity, tender joint count, and education level emerged as independent predictors of nociplastic-like pain features, whereas inflammatory markers (CRP, ESR) and DAS28 were excluded from the model. Conclusions: Nociplastic-like pain features are common in RA and are independently associated with pain intensity, joint tenderness, and psychosocial factors rather than inflammatory activity alone. Routine assessment of these features is essential for personalized pain management and underscores the importance of considering potential central sensitization mechanisms in addition to traditional anti-inflammatory therapies.

## Linked entities

- **Diseases:** rheumatoid arthritis (MONDO:0008383)

## Full-text entities

- **Genes:** IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** Fibromyalgia (MESH:D005356), neurological or psychiatric disorders (MESH:D001523), impaired (MESH:D060825), malignancy (MESH:D009369), synovitis (MESH:D013585), diabetes mellitus (MESH:D003920), sensory disturbances (MESH:D012678), joint (MESH:D007592), autoimmune or inflammatory rheumatic diseases (MESH:D012213), chronic kidney or liver disease (MESH:D051436), Inflammatory (MESH:D007249), injury to (MESH:D014947), MH (MESH:C535694), RA (MESH:D001172), nociplastic symptoms (MESH:D012816), neurological damage (MESH:D020196), Pain (MESH:D010146), sleep disturbance (MESH:D012893), nerve damage (MESH:D000080902), BP (MESH:D007022), allodynia (MESH:D006930), Chronic Illness (MESH:D002908), mood disturbances (MESH:D019964), SJC (MESH:D009845), Proinflammatory cytokines (MESH:D000080424), chronic pain (MESH:D059350), nerve lesions (MESH:D020426), neuropathic (MESH:D009437), autoimmune disease (MESH:D001327), peripheral neuropathy (MESH:D010523), functional (MESH:D003291), Fatigue (MESH:D005221), TJC (MESH:D063806)
- **Chemicals:** rituximab (MESH:D000069283), JAKi (-), tocilizumab (MESH:C502936)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12942023/full.md

---
Source: https://tomesphere.com/paper/PMC12942023