Background & Aims

Rheumatoid arthritis (RA) is the commonest inflammatory joint disease with major impact on people and health services. Patients with RA identify pain as their primary complaint. The overall pain experience is complex and multifaceted, comprising both sensory and emotional components. High disease activity is associated with RA pain. Persistent pain, despite adequate control of inflammation, indicates contributions from multiple pain mechanisms. Quantitative Sensory Testing (QST) is a reliable and valid method of measuring various indices of pain sensitivity in RA [1]. QST evidence indicates that CNS mechanisms of hyperalgesia contribute to RA pain [2]. This is in line with evidence demonstrating contribution of central mechanisms in pain severity in various musculoskeletal conditions [3]. This study aimed to ascertain what proportion of pain severity in RA is explained by indices of inflammation and central sensitisation.

Methods

In a clinical assessment session, individuals with RA were asked about their pain (0-10) over the past month (Now, Strongest, Average) and received physical (DAS28 swollen join count-D28SJ), imaging (ultrasound-US: synovial hypertrophy-SF, Power Doppler-PD), and laboratory (bloods-CRP) tests to ascertain current levels of inflammation. US scoring was according to EULAR [4]. QST comprised Pressure Pain detection Threshold (PPT), Temporal Summation (TS) and Conditioned Pain Modulation (CPM). QST test sites were the tibialis anterior (PPT-TA), medial joint line (PPT-MJL) and rectus femoris (TS) of the most painful knee, as well as the contralateral brachioradialis (PPT-BR, CPM) and ischaemic pain conditioning at the ipsilateral arm (CPM). Univariate unadjusted correlations measured associations between all variables. The proportion of pain severity in RA explained by inflammatory markers and QST indices of pain sensitivity was determined using regression models adjusted for age and sex.

Results

Ninety-five (n=95) people with RA pain (mean age: 65±10y, 77% female) were recruited from the Sherwood Forest Hospitals NHS Trust, UK. Levels of pain were (median [IQR]); Now: 5 [4 to 7], and Strongest: 8 [7 to 9], Average: 7 [5 to 8] over the past month. Levels of inflammation were; D28SJ (0-28): 3 [1 to 6], US-SF (0-48): 26 [21 to 30], US-PD (0-48): 8 [4 to 13], CRP (mg/l): 5 [2 to 9]. In bivariate analyses, each pain level measurement was correlated with some markers of inflammation (?=0.20 to 0.49, p<0.05), TS (?=0.21 to 0.24, p<0.05), and CPM (?=-0.22 to -0.30, p<0.05). In regression models, CRP remained significantly associated with each pain measurement (?=0.29 to 0.40, p<0.01). RA pain explained by inflammation in these models ranged from R2=0.15 to 0.23, p<0.01. When central sensitisation indices were also included, TS was associated with Pain-Now (?=0.22, p<0.05) and Pain-Strongest (?=0.24, p<0.05) and explained pain ranged from R2=0.16 to 0.24, p<0.01.

Conclusions

In cross-sectional analyses in individuals with RA, markers of disease activity and some QST indices of central sensitisation together may explain up to 23% of experienced pain. Despite such findings, a significant proportion of pain remains unexplained by markers of inflammation and measurements of pain sensitivity. It is likely that clinical and social factors reflecting the biopsychosocial nature of pain, when taken into consideration or explored longitudinally, could explain a larger proportion of the experienced pain. Future research should explore whether markers of inflammation or pain sensitivity predict future pain. Such insight may lead to better prediction of treatment outcomes in RA.

References

[1].Brady SM, Georgopoulos V, van Zanten JJV, et al. 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. Pain Reports. 2023;8(6):e1102.
[2].Meeus M, Vervisch S, De Clerck LS, Moorkens G, Hans G, Nijs J. Central sensitization in patients with rheumatoid arthritis: a systematic literature review. Elsevier; 2012:556-567.
[3].Georgopoulos V, Akin-Akinyosoye K, Zhang W, McWilliams DF, Hendrick P, Walsh DA. Quantitative Sensory Testing (QST) and predicting outcomes for musculoskeletal pain, disability and negative affect: a systematic review and meta-analysis. Pain. 2019;160(9):1920.
[4].D’Agostino M-A, Terslev L, Aegerter P, et al. Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce—Part 1: definition and development of a standardised, consensus-based scoring system. RMD open. 2017;3(1)

Presenting Author

Vasileios Georgopoulos

Poster Authors

Vasileios Georgopoulos

PhD

The University of Nottingham

Lead Author

E-mail

Stephanie Smith

University of Nottingham, Pain Centre Versus Arthritis

Lead Author

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Eamonn Ferguson

PhD

School of Psychology, University of Nottingham, UK

Lead Author

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Richard Wakefield

BM

Leeds Institute of Rheumatic and Musculoskeletal Medicine, and NIHR Leeds Biomedical Research Centre

Lead Author

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Deborah Wilson

Rheumatology, Sherwood Forest Hospitals NHS Foundation Trust, Nottinghamshire, UK

Lead Author

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Philip Buckley

Rheumatology, Sherwood Forest Hospitals NHS Foundation Trust, Nottinghamshire, UK

Lead Author

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Dorothy Platts

Independent Consultant, Nottingham, UK

Lead Author

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Suzan Ledbury

Independent Consultant, Nottingham, UK

Lead Author

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David Walsh

MD

School of Medicine, University of Nottingham

Lead Author

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Topics

  • Assessment and Diagnosis