J Rheum Dis.  2023 Jul;30(3):176-184. 10.4078/jrd.2023.0009.

The effect of central sensitization on disease activity measures, quality of life and clinical parameters in axial spondyloarthritis: a cross-sectional study

• Şaş S
• Cengiz G
• Kaplan H

• KMID: 2543944
• DOI: http://doi.org/10.4078/jrd.2023.0009

Abstract

Objective
Despite biological drug therapy, pain remains a persistent complaint in patients with axial spondyloarthritis (axSpA). We aimed to investigate the effect of central sensitization (CS) on disease activity measures, quality of life, and clinical parameters in axSpA patients.
Methods
We consecutively recruited axSpA patients who were followed up at our rheumatology outpatient clinic, and age- and sex-matched controls in this cross-sectional study. The central sensitization inventory, douleur neuropathique 4 (DN4) questions, and 2010 American College of Rheumatology fibromyalgia (FM) diagnostic criteria were applied to all individuals. The patients’ clinical parameters were recorded. The data of the patient and control groups were compared.
Results
Of the 116 axSpA patients (57 female) and 95 controls (46 female) who participated in this study, CS was determined in 46.6% of axSpA patients and 13.7% of controls (p<0.001). Patients with CS exhibited high disease activity, and poor quality of life and functionality than without it (all p<0.001). The median CS, frequency of FM and frequency of neuropathic pain were higher in patients than in the controls (all p<0.001). CS-related conditions, including anxiety and depression, were higher in axSpA patients than in controls (both p<0.05).
Conclusion
The results showed that CS was common in axSpA patients, and patients with CS had higher disease activity, worse quality of life, and worse functional status than those without CS.

Keyword

Central sensitization; Pain; Axial spondyloarthritis; Quality of life

Reference

1. Danve A, Deodhar A. 2022; Treatment of axial spondyloarthritis: an update. Nat Rev Rheumatol. 18:205–16. DOI: 10.1038/s41584-022-00761-z. PMID: 35273385.

2. Rudwaleit M, van der Heijde D, Landewé R, Listing J, Akkoc N, Brandt J, et al. 2009; The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 68:777–83. Erratum. DOI: 10.1136/ard.2009.108233corr1. PMID: 31088800.

3. Zhu W, He X, Cheng K, Zhang L, Chen D, Wang X, et al. 2019; Ankylosing spondylitis: etiology, pathogenesis, and treatments. Bone Res. 7:22. DOI: 10.1038/s41413-019-0057-8. PMID: 31666997. PMCID: PMC6804882.

4. Pathan EMI, Inman RD. 2021; Pain in axial spondyloarthritis: insights from immunology and brain imaging. Rheum Dis Clin North Am. 47:197–213. DOI: 10.1016/j.rdc.2020.12.007. PMID: 33781490.

5. Magrey MN, Mease PJ. 2021; Pain in axial spondyloarthritis: more to it than just inflammation. J Rheumatol. 48:1632–4. DOI: 10.3899/jrheum.210137. PMID: 33934079.

6. Ji RR, Nackley A, Huh Y, Terrando N, Maixner W. 2018; Neuroinflammation and central sensitization in chronic and widespread pain. Anesthesiology. 129:343–66. DOI: 10.1097/ALN.0000000000002130. PMID: 29462012. PMCID: PMC6051899.

7. Woolf CJ. 2011; Central sensitization: implications for the diagnosis and treatment of pain. Pain. 152(3 Suppl):S2–15. DOI: 10.1016/j.pain.2010.09.030. PMID: 20961685. PMCID: PMC3268359.

8. Adami G, Gerratana E, Atzeni F, Benini C, Vantaggiato E, Rotta D, et al. 2021; Is central sensitization an important determinant of functional disability in patients with chronic inflammatory arthritides? Ther Adv Musculoskelet Dis. 13:1759720X21993252. DOI: 10.1177/1759720X21993252. PMID: 33643445. PMCID: PMC7890747.

9. Dumolard A, Lefaucheur JP, Hodaj E, Liateni Z, Payen JF, Hodaj H. 2023; Central sensitization and small-fiber neuropathy are associated in patients with fibromyalgia. Clin J Pain. 39:8–14. DOI: 10.1097/AJP.0000000000001085. PMID: 36524768.

10. Kieskamp SC, Paap D, Carbo MJG, Wink F, Bos R, Bootsma H, et al. 2022; Central sensitization has major impact on quality of life in patients with axial spondyloarthritis. Semin Arthritis Rheum. 52:151933. DOI: 10.1016/j.semarthrit.2021.11.006. PMID: 35033996.

11. Kieskamp SC, Paap D, Carbo MJG, Wink F, Bos R, Bootsma H, et al. 2021; Central sensitization, illness perception and obesity should be considered when interpreting disease activity in axial spondyloarthritis. Rheumatology (Oxford). 60:4476–85. DOI: 10.1093/rheumatology/keab019. PMID: 33492397. PMCID: PMC8487271.

12. Aykurt Karlıbel I, Kasapoğlu Aksoy M. 2023; The relationship between central sensitization and disease activity, quality of life, and sleep quality among patients with axial spondyloarthritis. Ir J Med Sci. 192:481–9. DOI: 10.1007/s11845-022-02957-4. PMID: 35226249.

13. Mogard E, Lindqvist E, Bremander A, Bergman S. 2019; Risk factors for development and persistence of chronic widespread pain in spondyloarthritis: a population-based two-year follow-up study. Scand J Rheumatol. 48:460–8. DOI: 10.1080/03009742.2019.1602163. PMID: 31244357.

14. Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, Landewé R, van ver Tempel H, Mielants H, et al. 2003; Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis. 62:127–32. DOI: 10.1136/ard.62.2.127. PMID: 12525381. PMCID: PMC1754445.

15. Calin A, Garrett S, Whitelock H, Kennedy LG, O'Hea J, Mallorie P, et al. 1994; A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol. 21:2281–5.

16. Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. 1994; A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol. 21:2286–91.

17. Jenkinson TR, Mallorie PA, Whitelock HC, Kennedy LG, Garrett SL, Calin A. 1994; Defining spinal mobility in ankylosing spondylitis (AS). The Bath AS Metrology Index. J Rheumatol. 21:1694–8.

18. van der Heijde D, Lie E, Kvien TK, Sieper J, Van den Bosch F, Listing J, et al. 2009; ASDAS, a highly discriminatory ASAS-endorsed disease activity score in patients with ankylosing spondylitis. Ann Rheum Dis. 68:1811–8. DOI: 10.1136/ard.2008.100826. PMID: 19060001.

19. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, et al. 2010; The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken). 62:600–10. DOI: 10.1002/acr.20140. PMID: 20461783.

20. Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, et al. 2005; Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain. 114:29–36. DOI: 10.1016/j.pain.2004.12.010. PMID: 15733628.

21. Coronado RA, George SZ. 2018; The Central Sensitization Inventory and Pain Sensitivity Questionnaire: an exploration of construct validity and associations with widespread pain sensitivity among individuals with shoulder pain. Musculoskelet Sci Pract. 36:61–7. DOI: 10.1016/j.msksp.2018.04.009. PMID: 29751194. PMCID: PMC6671673.

22. Guler MA, Celik OF, Ayhan FF. 2020; The important role of central sensitization in chronic musculoskeletal pain seen in different rheumatic diseases. Clin Rheumatol. 39:269–74. DOI: 10.1007/s10067-019-04749-1. PMID: 31446538.

23. Pinho-Ribeiro FA, Verri WA Jr, Chiu IM. 2017; Nociceptor sensory neuron-immune interactions in pain and inflammation. Trends Immunol. 38:5–19. DOI: 10.1016/j.it.2016.10.001. PMID: 27793571. PMCID: PMC5205568.

24. Serrano-Ibáñez ER, Esteve R, Ramírez-Maestre C, Ruiz-Párraga GT, López-Martínez AE. 2021; Chronic pain in the time of COVID-19: stress aftermath and central sensitization. Br J Health Psychol. 26:544–52. DOI: 10.1111/bjhp.12483. PMID: 33099793.

25. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RL, et al. 2016; 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 46:319–29. DOI: 10.1016/j.semarthrit.2016.08.012. PMID: 27916278.

26. Koca TT, Göğebakan H, Çetin G. 2019; Should central sensitization and neuropathic pain be considered in disease activity and treatment decision in axial ankylosing spondilitis? Cukurova Med J. 44(Suppl 1):1–10. DOI: 10.17826/cumj.503652.

27. Baraliakos X, Regel A, Kiltz U, Menne HJ, Dybowski F, Igelmann M, et al. 2018; Patients with fibromyalgia rarely fulfil classification criteria for axial spondyloarthritis. Rheumatology (Oxford). 57:1541–7. DOI: 10.1093/rheumatology/kex318. PMID: 28968885.

28. Bello N, Etcheto A, Béal C, Dougados M, Moltó A. 2016; Evaluation of the impact of fibromyalgia in disease activity and treatment effect in spondyloarthritis. Arthritis Res Ther. 18:42. DOI: 10.1186/s13075-016-0943-z. PMID: 26860612. PMCID: PMC4748456.

29. Ablin JN, Eshed I, Berman M, Aloush V, Wigler I, Caspi D, et al. 2017; Prevalence of axial spondyloarthritis among patients with fibromyalgia: a magnetic resonance imaging study with application of the Assessment of SpondyloArthritis International Society classification criteria. Arthritis Care Res (Hoboken). 69:724–9. DOI: 10.1002/acr.22967. PMID: 27390225.

30. Bouhassira D, Lantéri-Minet M, Attal N, Laurent B, Touboul C. 2008; Prevalence of chronic pain with neuropathic characteristics in the general population. Pain. 136:380–7. DOI: 10.1016/j.pain.2007.08.013. PMID: 17888574.