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30-05-2018 | Rheumatoid arthritis | Article

The course of pain hypersensitivity according to painDETECT in patients with rheumatoid arthritis initiating treatment: results from the prospective FRAME-cohort study

Journal: Arthritis Research & Therapy

Authors: Signe Rifbjerg-Madsen, Anton Wulf Christensen, Mikael Boesen, Robin Christensen, Bente Danneskiold-Samsøe, Henning Bliddal, Lene Dreyer, Henning Locht, Kirstine Amris

Publisher: BioMed Central

Abstract

Background

Evidence is emerging that pain in rheumatoid arthritis (RA) exists without underlying inflammation. Our objective was to evaluate the prognostic value of pain classification at treatment initiation using the painDETECT questionnaire (PDQ). Outcomes were change in DAS28-CRP and RAMRIS synovitis score.

Methods

RA patients initiating a disease-modifying anti-rheumatic drug (DMARD) or initiating/ switching a biological agent were included. Follow-up time was 4 months. Clinical examination, imaging (MRI, dynamic contrast-enhanced MRI (DCE-MRI)), and patient-reported outcomes were undertaken. The PDQ was used to differentiate pain mechanisms. Mean change (95% CI) was calculated using ANCOVA. Multivariable regression models were used to determine a prognostic value.

Results

A total of 102 patients were included; 75 were enrolled for MRI. Mean changes in baseline variables were greatest in the high PDQ classification group (> 18), while limited in the intermediate group (13–18). The 12 patients with high baseline PDQ score all changed pain classification group. No prognostic value of PDQ pain classification was found in relation to change of DAS28-CRP, RAMRIS score, or VAS pain. In the unadjusted model, RAMRIS score at baseline was associated with change in DAS28-CRP. The exploratory variables of DCE-MRI did not differ from other inflammatory variables.

Conclusions

In RA patients a high PDQ score (non-nociceptive pain) at baseline was not associated with worse outcomes, in fact these patients had numerically greater improvement in DAS28-CRP. However, pain classification by PDQ was not independently associated with change in DAS28-CRP, RAMRIS score, or VAS pain in the prognostic models.
Furthermore, patients classified with a high baseline PDQ score changed pain classification group. Patients with unclear pain mechanism had reduced numerically treatment response.

Trial registration

The study was approved by the Regional Ethics Committee of the Capital of Denmark April 18 2013; identification number H-3-2013-049.
Literature
1.
Schaible HG, von Banchet GS, Boettger MK, Brauer R, Gajda M, Richter F, et al. The role of proinflammatory cytokines in the generation and maintenance of joint pain. Ann N Y Acad Sci. 2010;1193:60–9.CrossRefPubMed
2.
Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73(3):492–509.CrossRefPubMed
3.
Meeus M, Vervisch S, De Clerck LS, Moorkens G, Hans G, Nijs J. Central sensitization in patients with rheumatoid arthritis: a systematic literature review. Semin Arthritis Rheum. 2012;41(4):556–67.CrossRefPubMed
4.
Lee YC, Cui J, Lu B, Frits ML, Iannaccone CK, Shadick NA, et al. Pain persists in DAS28 rheumatoid arthritis remission but not in ACR/EULAR remission: a longitudinal observational study. Arthritis Res Ther. 2011;13(3):R83.CrossRefPubMedPubMedCentral
5.
Wolfe F, Michaud K. Severe rheumatoid arthritis (RA), worse outcomes, comorbid illness, and sociodemographic disadvantage characterize ra patients with fibromyalgia. J Rheumatol. 2004;31(4):695–700.PubMed
6.
Lee YC, Nassikas NJ, Clauw DJ. The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia. Arthritis Res Ther. 2011;13(2):211.CrossRefPubMedPubMedCentral
7.
Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3 Suppl):S2–15.CrossRefPubMed
8.
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO III, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–81.CrossRefPubMed
9.
Freynhagen R, Baron R, Gockel U, Tolle TR. painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin. 2006;22(10):1911–20.CrossRefPubMed
10.
Amris K, Jespersen A, Bliddal H. Self-reported somatosensory symptoms of neuropathic pain in fibromyalgia and chronic widespread pain correlate with tender point count and pressure-pain thresholds. Pain. 2010;151(3):664–9.CrossRefPubMed
11.
Gwilym SE, Keltner JR, Warnaby CE, Carr AJ, Chizh B, Chessell I, et al. Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients. Arthritis Rheum. 2009;61(9):1226–34.CrossRefPubMed
12.
Koroschetz J, Rehm SE, Gockel U, Brosz M, Freynhagen R, Tolle TR, et al. Fibromyalgia and neuropathic pain--differences and similarities. A comparison of 3057 patients with diabetic painful neuropathy and fibromyalgia. BMC Neurol. 2011;11:55.CrossRefPubMedPubMedCentral
13.
Ahmed S, Magan T, Vargas M, Harrison A, Sofat N. Use of the painDETECT tool in rheumatoid arthritis suggests neuropathic and sensization components in pain reporting. J Pain Res. 2014;7:579–88.PubMedPubMedCentral
14.
Koop SM, Ten Klooster PM, Vonkeman HE, Steunebrink LM, van de Laar MA. Neuropathic-like pain features and cross-sectional associations in rheumatoid arthritis. Arthritis Res Ther. 2015;17(1):237.CrossRefPubMedPubMedCentral
15.
Wu Q, Inman RD, Davis KD. Neuropathic pain in ankylosing spondylitis - a psychophysics and brain imaging study. Arthritis Rheum. 2013;65(6):1494–503.CrossRefPubMed
16.
Ostergaard M, Peterfy C, Conaghan P, McQueen F, Bird P, Ejbjerg B, et al. OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Core set of MRI acquisitions, joint pathology definitions, and the OMERACT RA-MRI scoring system. J Rheumatol. 2003;30(6):1385–6.PubMed
17.
Axelsen MB, Stoltenberg M, Poggenborg RP, Kubassova O, Boesen M, Bliddal H, et al. Dynamic gadolinium-enhanced magnetic resonance imaging allows accurate assessment of the synovial inflammatory activity in rheumatoid arthritis knee joints: a comparison with synovial histology. Scand J Rheumatol. 2012;41(2):89–94.CrossRefPubMed
18.
Ostergaard M, Stoltenberg M, Lovgreen-Nielsen P, Volck B, Jensen CH, Lorenzen I. Magnetic resonance imaging-determined synovial membrane and joint effusion volumes in rheumatoid arthritis and osteoarthritis: comparison with the macroscopic and microscopic appearance of the synovium. Arthritis Rheum. 1997;40(10):1856–67.CrossRefPubMed
19.
Christensen AW, Rifbjerg-Madsen S, Christensen R, Amris K, Taylor PC, Locht H, et al. Temporal summation of pain and ultrasound Doppler activity as predictors of treatment response in patients with rheumatoid arthritis: protocol for the Frederiksberg hospitals Rheumatoid Arthritis, pain assessment and Medical Evaluation (FRAME-cohort) study. BMJ Open. 2014;4(1):e004313.CrossRefPubMedPubMedCentral
20.
Rifbjerg-Madsen S, Christensen AW, Boesen M, Christensen R, Danneskiold-Samsoe B, Bliddal H, et al. Can the painDETECT Questionnaire score and MRI help predict treatment outcome in rheumatoid arthritis: protocol for the Frederiksberg hospital's Rheumatoid Arthritis, pain assessment and Medical Evaluation (FRAME-cohort) study. BMJ Open. 2014;4(11):e006058.CrossRefPubMedPubMedCentral
21.
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31(3):315–24.CrossRefPubMed
22.
Rifbjerg-Madsen S, Waehrens EE, Danneskiold-Samsoe B, Amris K. Psychometric properties of the painDETECT questionnaire in rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: Rasch analysis and test-retest reliability. Health Qual Life Outcomes. 2017;15(1):110.CrossRefPubMedPubMedCentral
23.
Gudbergsen H, Bartels EM, Krusager P, Waehrens EE, Christensen R, Danneskiold-Samsoe B, et al. Test-retest of computerized health status questionnaires frequently used in the monitoring of knee osteoarthritis: a randomized crossover trial. BMC Musculoskelet Disord. 2011;12:190.CrossRefPubMedPubMedCentral
24.
Thorsen H, Hansen TM, McKenna SP, Sorensen SF, Whalley D. Adaptation into Danish of the Stanford Health Assessment Questionnaire (HAQ) and the Rheumatoid Arthritis Quality of Life Scale (RAQoL). Scand J Rheumatol. 2001;30(2):103–9.CrossRefPubMed
25.
Bjorner JB, Thunedborg K, Kristensen TS, Modvig J, Bech P. The Danish SF-36 Health Survey: translation and preliminary validity studies. J Clin Epidemiol. 1998;51(11):991–9.CrossRefPubMed
26.
Bech P, Kastrup M, Rafaelsen OJ. Mini-compendium of rating scales for states of anxiety depression mania schizophrenia with corresponding DSM-III syndromes. Acta Psychiatr Scand Suppl. 1986;326:1–37.PubMed
27.
Bech P, Rasmussen NA, Olsen LR, Noerholm V, Abildgaard W. The sensitivity and specificity of the Major Depression Inventory, using the Present State Examination as the index of diagnostic validity. J Affect Disord. 2001;66(2–3):159–64.CrossRefPubMed
28.
Ejbjerg B, McQueen F, Lassere M, Haavardsholm E, Conaghan P, O'Connor P, et al. The EULAR-OMERACT rheumatoid arthritis MRI reference image atlas: the wrist joint. Ann Rheum Dis. 2005;64(Suppl 1):i23–47.CrossRefPubMedPubMedCentral
29.
Haavardsholm EA, Ostergaard M, Ejbjerg BJ, Kvan NP, Uhlig TA, Lilleas FG, et al. Reliability and sensitivity to change of the OMERACT rheumatoid arthritis magnetic resonance imaging score in a multireader, longitudinal setting. Arthritis Rheum. 2005;52(12):3860–7.CrossRefPubMed
30.
Boesen M, Kubassova O, Parodi M, Bliddal H, Innocenti S, Garlaschi G, et al. Comparison of the manual and computer-aided techniques for evaluation of wrist synovitis using dynamic contrast-enhanced MRI on a dedicated scanner. Eur J Radiol. 2011;77(2):202–6.CrossRefPubMed
31.
Axelsen MB, Poggenborg RP, Stoltenberg M, Kubassova O, Boesen M, Horslev-Petersen K, et al. Reliability and responsiveness of dynamic contrast-enhanced magnetic resonance imaging in rheumatoid arthritis. Scand J Rheumatol. 2013;42(2):115–22.CrossRefPubMed
32.
Ballegaard C, Riis RG, Bliddal H, Christensen R, Henriksen M, Bartels EM, et al. Knee pain and inflammation in the infrapatellar fat pad estimated by conventional and dynamic contrast-enhanced magnetic resonance imaging in obese patients with osteoarthritis: a cross-sectional study. Osteoarthr Cartil. 2014;22(7):933–40.CrossRefPubMed
33.
Bandak E, Boesen M, Bliddal H, Riis RG, Gudbergsen H, Henriksen M. Associations between muscle perfusion and symptoms in knee osteoarthritis: a cross sectional study. Osteoarthr Cartil. 2015;23(10):1721–7.CrossRefPubMed
34.
Boesen M, Kubassova O, Bouert R, Axelsen MB, Ostergaard M, Cimmino MA, et al. Correlation between computer-aided dynamic gadolinium-enhanced MRI assessment of inflammation and semi-quantitative synovitis and bone marrow oedema scores of the wrist in patients with rheumatoid arthritis--a cohort study. Rheumatology (Oxford). 2012;51(1):134–43.CrossRef
35.
Cimmino MA, Parodi M, Zampogna G, Boesen M, Kubassova O, Barbieri F, et al. Dynamic contrast-enhanced, extremity-dedicated MRI identifies synovitis changes in the follow-up of rheumatoid arthritis patients treated with rituximab. Clin Exp Rheumatol. 2014;32(5):647–52.PubMed
36.
Christensen AW, Rifbjerg-Madsen S, Christensen R, Dreyer L, Tillingsoe H, Seven S, et al. Non-nociceptive pain in rheumatoid arthritis is frequent and affects disease activity estimation: cross-sectional data from the FRAME study. Scand J Rheumatol. 2016;18:1–9.
37.
Christensen AW, Rifbjerg-Madsen S, Christensen R, Dreyer L, Boesen M, Ellegaard K, et al. Ultrasound Doppler but not temporal summation of pain predicts DAS28 response in rheumatoid arthritis: a prospective cohort study. Rheumatology (Oxford). 2016;55(6):1091–8.CrossRef
38.
Ostergaard M, Moller-Bisgaard S. Optimal use of MRI in clinical trials, clinical care and clinical registries of patients with rheumatoid arthritis. Clin Exp Rheumatol. 2014;32(5 Suppl 85):S-22.
39.
Suter LG, Fraenkel L, Braithwaite RS. Role of magnetic resonance imaging in the diagnosis and prognosis of rheumatoid arthritis. Arthritis Care Res (Hoboken ). 2011;63(5):675–88.CrossRef
40.
Brendbekken R, Eriksen HR, Grasdal A, Harris A, Hagen EM, Tangen T. Return to work in patients with chronic musculoskeletal pain: multidisciplinary intervention versus brief intervention: a randomized clinical trial. J Occup Rehabil. 2017;27(1):82-91.
41.
Tse MM, Yeung SS, Lee PH, Ng SS. Effects of a peer-led pain management program for nursing home residents with chronic pain: a pilot study. Pain Med. 2016;18.
42.
Amris K, Luta G, Christensen R, Danneskiold-Samsoe B, Bliddal H, Waehrens EE. Predictors of improvement in observed functional ability in patients with fibromyalgia as an outcome of rehabilitation. J Rehabil Med. 2016;48(1):65-71.
43.
Amris K, Waehrens EE, Christensen R, Bliddal H, Danneskiold-Samsoe B. Interdisciplinary rehabilitation of patients with chronic widespread pain: primary endpoint of the randomized, nonblinded, parallel-group IMPROvE trial. Pain. 2014;155(7):1356–64.CrossRefPubMed
44.
Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. 2010;9(8):807–19.CrossRefPubMed
45.
Bennett MI, Attal N, Backonja MM, Baron R, Bouhassira D, Freynhagen R, et al. Using screening tools to identify neuropathic pain. Pain. 2007;127(3):199–203.CrossRefPubMed
46.
Rehm SE, Koroschetz J, Gockel U, Brosz M, Freynhagen R, Tolle TR, et al. A cross-sectional survey of 3035 patients with fibromyalgia: subgroups of patients with typical comorbidities and sensory symptom profiles. Rheumatology (Oxford). 2010;49(6):1146–52.CrossRef
47.
Hochman JR, Gagliese L, Davis AM, Hawker GA. Neuropathic pain symptoms in a community knee OA cohort. Osteoarthr Cartil. 2011;19(6):647–54.CrossRefPubMed
48.
Hochman JR, Davis AM, Elkayam J, Gagliese L, Hawker GA. Neuropathic pain symptoms on the modified painDETECT correlate with signs of central sensitization in knee osteoarthritis. Osteoarthr Cartil. 2013;21(9):1236–42.CrossRefPubMed
49.
Moreton BJ, Tew V, das NR WM, Walsh DA, Lincoln NB. Pain phenotype in patients with knee osteoarthritis: classification and measurement properties of painDETECT and self-report Leeds assessment of neuropathic symptoms and signs scale in a cross-sectional study. Arthritis Care Res (Hoboken ). 2015;67(4):519–28.CrossRef
50.
Boesen M, Kubassova O, Cimmino MA, Ostergaard M, Taylor P, Danneskiold-Samsoe B, et al. Dynamic contrast-enhanced MRI can monitor the very early inflammatory treatment response upon intra-articular steroid injection in the knee joint: a case report with review of the literature. Arthritis. 2011;2011:578252.CrossRefPubMedPubMedCentral
51.
Conaghan PG, Ostergaard M, Bowes MA, Wu C, Fuerst T, van der Heijde D, et al. Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques. Ann Rheum Dis. 2016;75(6):1024–33.CrossRefPubMedPubMedCentral
52.
Hess A, Axmann R, Rech J, Finzel S, Heindl C, Kreitz S, et al. Blockade of TNF-alpha rapidly inhibits pain responses in the central nervous system. Proc Natl Acad Sci U S A. 2011;108(9):3731–6.CrossRefPubMedPubMedCentral