TYPES OF PAIN IN RHEUMATOID ARTHRITIS: CENTRALIZATION MECHANISMS, RISK FACTORS, AND TREATMENT APPROACHES

Natalia Musialik; Maciej Magiera; Barbara Starosta; Monika Pelczar; Bartosz Brzychcy; Karolina Brzychcy; Karolina Paks; Zuzanna Gajda; Ewa Jench

doi:10.31435/ijitss.3(47).2025.3895

Authors

Natalia Musialik Central Teaching Hospital of the Medical University of Lodz, ul. Pomorska 251, 92-213 Łódź, Poland https://orcid.org/0009-0004-5249-6420
Maciej Magiera Central Teaching Hospital of the Medical University of Lodz, ul. Pomorska 251, 92-213 Łódź, Poland https://orcid.org/0009-0002-9679-0838
Barbara Starosta Clinical Hospital No. 2 in Łódź, ul. Stefana Żeromskiego 113, 90-549 Łódź, Poland https://orcid.org/0009-0008-8750-9112
Monika Pelczar T. Marciniak Lower Silesian Specialist Hospital – Emergency Medicine Centre, ul. Generała Augusta Emila Fieldorfa 2, 54-049 Wrocław, Poland https://orcid.org/0009-0003-0952-1582
Bartosz Brzychcy Provincial Hospital Complex named after Dr. Roman Ostrzycki in Konin, ul. Szpitalna 45, 62-504 Konin, Poland https://orcid.org/0009-0003-2828-0382
Karolina Brzychcy Provincial Hospital Complex named after Dr. Roman Ostrzycki in Konin, ul. Szpitalna 45, 62-504 Konin, Poland https://orcid.org/0009-0009-4930-4375
Karolina Paks Independent Public Health Care Facility of the Ministry of Internal Affairs and Administration in Katowice named after Sergeant Grzegorz Załoga, ul. Wita Stwosza 39-41, 40-042 Katowice, Poland https://orcid.org/0009-0001-3804-2041
Zuzanna Gajda University Clinical Hospital No. 2 in Łódź, ul. Stefana Żeromskiego 113, 90-549 Łódź, Poland https://orcid.org/0009-0006-9255-2102
Ewa Jench T. Marciniak Lower Silesian Specialist Hospital – Emergency Medicine Centre, ul. Generała Augusta Emila Fieldorfa 2, 54-049 Wrocław, Poland https://orcid.org/0009-0003-1680-1101

DOI:

https://doi.org/10.31435/ijitss.3(47).2025.3895

Keywords:

Rheumatoid Arthritis, Fibromyalgia, Neuropathic Pain, Chronic Pain, Central Sensitization, Pain Measurement

Abstract

Introduction and aim: One of the main complaints in rheumatoid arthritis (RA) is pain. It may result not only from inflammation and joint damage, but also from neuropathy and central sensitization, leading to nociplastic (central) pain. This type of pain is often overlooked, as it does not correlate with visible musculoskeletal pathology. Its pathogenesis is not fully understood, and both diagnosis and treatment are challenging. The aim of this paper is to review the types of pain in RA, with a particular focus on nociplastic pain—its causes, clinical presentation, diagnostics, and therapy.

Materials and Methods: A review of the available scientific literature on RA was conducted using PubMed, Google Scholar, and Embase databases.

Conclusion: Pain in RA can be nociceptive, neuropathic, or nociplastic. Nociplastic pain is driven by central sensitization, influenced by cytokines (IL-1, IL-6, TNF-α), microglial activation, and synaptic transmission imbalance. Diagnosis relies on questionnaires (e.g., Central Sensitization Index – CSI) and sensory testing (e.g., Quantitative Sensory Testing – QST). Treatment includes pharmacological options (paracetamol, benzodiazepines, opioids, SNRIs, naltrexone, TNF-α inhibitors, pregabalin, gabapentin, Sarilumab, JAK1/JAK2 inhibitors) and non-pharmacological methods: pain neuroscience education (PNE), cognitive behavioral therapy (CBT), stress reduction, and tailored physical activity.

References

Venetsanopoulou, A. I., Alamanos, Y., Voulgari, P. V., & Drosos, A. A. (2023). Epidemiology and risk factors for rheumatoid arthritis development. Mediterranean Journal of Rheumatology, 34(4), 404–413. https://doi.org/10.31138/mjr.301223.eaf

Sobierajski, T. (2019). Codzienność z reumatoidalnym zapaleniem stawów: Wiedza, postawy i psychospołeczne doświadczenia osób z RZS. Warszawa: KnowPR we współpracy z Ogólnopolską Federacją Stowarzyszeń Reumatyków „REF”. https://spartanska.pl/wp-content/uploads/RZS_raport_web.pdf

International Association for the Study of Pain. (2020, June 23). IASP announces revised definition of pain. International Association for the Study of Pain. https://www.iasp-pain.org/publications/iasp-news/iasp-announces-revised-definition-of-pain/

Zhang, A., & Lee, Y. C. (2018). Mechanisms for joint pain in rheumatoid arthritis (RA): From cytokines to central sensitization. Current Osteoporosis Reports, 16(5), 603–610. https://doi.org/10.1007/s11914-018-0473-5

Kidd, B. L., & Urban, L. A. (2001). Mechanisms of inflammatory pain. British Journal of Anaesthesia, 87(1), 3–11. https://doi.org/10.1093/bja/87.1.3

Melzack, R. (1999). From the gate to the neuromatrix. Pain, 82(Suppl. 6), S121–S126. https://doi.org/10.1016/S0304-3959(99)00145-1

Ossipov, M. H., Morimura, K., & Porreca, F. (2014). Descending pain modulation and chronification of pain. Current Opinion in Supportive and Palliative Care, 8(2), 143–151. https://doi.org/10.1097/SPC.0000000000000055

Biddle, K., & Sofat, N. (2020). Understanding the mechanisms of pain in rheumatoid arthritis. In IntechOpen. https://doi.org/10.5772/intechopen.93829

Finnerup, N. B., Kuner, R., & Jensen, T. S. (2021). Neuropathic pain: From mechanisms to treatment. Physiological Reviews, 101(1), 259–301. https://doi.org/10.1152/physrev.00045.2019

Kosińska, B., Turczyn, P., Wesołowski, K., Tarnacka, B., & Malec-Milewska, M. (2020). Centralna sensytyzacja u pacjentów z przewlekłym bólem krzyża, część 1 – patofizjologia i diagnostyka. Ból, 21(1), 29–38. https://doi.org/10.5604/01.3001.0014.3421

McWilliams, D. F., & Walsh, D. A. (2017). Pain mechanisms in rheumatoid arthritis. Clinical and Experimental Rheumatology, 35(Suppl. 107), 94–101. https://www.clinexprheumatol.org/abstract.asp?a=12176

Abdelrazek, M. S., Elnaggar, B. M. A., Ahmed, A. M., & Mohamed, M. S. E. (2025). Clinical, neurophysiological, and radiological characteristics of peripheral neuropathy in patients with rheumatoid arthritis: A cross-sectional observational study. Journal of the Neurological Sciences, 473, 123523. https://doi.org/10.1016/j.jns.2025.123523

Abdullah, A. Y., Yousif, R. A., Suliman, A. G., Ibn Idris, A. A., Hassan, S. A., Ali, S. I., Alshoabi, S. A., Algorashi, E. M., Mohammed, B. N., & Elzaki, M. (2023). The impact of rheumatoid arthritis (RA) in median nerve area in the wrist joint: A case-control study. Cureus, 15(5), e38580. https://doi.org/10.7759/cureus.38580

George, R. J., Frechette, N., Oviedo, M., Javed, I., Achenbach, S. J., Lennon, R. J., Kimbrough, B. A., Joerns, E. K., Kronzer, V. L., Gingery, A., Davis, J. M. III, Crowson, C. S., & Myasoedova, E. (2025). Carpal tunnel syndrome (CTS) is an early underrecognized feature of rheumatoid arthritis (RA): A population-based study of CTS occurrence before and after RA incidence. Arthritis Care & Research. Advance online publication. https://doi.org/10.1002/acr.25566

Lee, K. H., Lee, C. H., Lee, B. G., Park, J. S., & Choi, W. S. (2015). The incidence of carpal tunnel syndrome in patients with rheumatoid arthritis. International Journal of Rheumatic Diseases, 18(1), 52–57. https://doi.org/10.1111/1756-185X.12445

Martin, K., Bentaberry, F., Dumoulin, C., Miremont-Salamé, G., Haramburu, F., Dehais, J., & Schaeverbeke, T. (2007). Peripheral neuropathy associated with leflunomide: Is there a risk patient profile? Pharmacoepidemiology and Drug Safety, 16(1), 74–78. https://doi.org/10.1002/pds.1282

Richards, B. L., Spies, J., McGill, N., Richards, G. W., Vaile, J., Bleasel, J. F., & Youssef, P. P. (2007). Effect of leflunomide on the peripheral nerves in rheumatoid arthritis. Internal Medicine Journal, 37(2), 101–107. https://doi.org/10.1111/j.1445-5994.2007.01266.x

Kaur, G., Barclay, M., Mitchell, J., Jordan, S., & Stebbings, S. (2024). The prevalence and clinical features of leflunomide-associated peripheral neuropathy in patients with rheumatic disease in a New Zealand cohort. International Journal of Rheumatic Diseases, 27(9), e15317. https://doi.org/10.1111/1756-185X.15317

Rekik, S., Ben Amou, A., Rahmouni, S., et al. (2024). AB0635 Vasculitis in rheumatoid arthritis: Multiple facets to look for! Annals of the Rheumatic Diseases, 83(Suppl. 1), 1603. https://doi.org/10.1136/annrheumdis-2024-eular.6237

Kaeley, N., Ahmad, S., Pathania, M., & Kakkar, R. (2019). Prevalence and patterns of peripheral neuropathy in patients of rheumatoid arthritis. Journal of Family Medicine and Primary Care, 8(1), 22–26. https://doi.org/10.4103/jfmpc.jfmpc_260_18

Muley, A., Bhaliya, B., Mitra, S., Nakum, D., Kuldeep, V., et al. (2023). Rheumatoid arthritis presenting as vasculitis and neuropathy: A case report and review. Journal of Clinical Images and Medical Case Reports, 4(6), 2478. https://doi.org/10.52768/2766-7820/2478

Bartels, C. M., & Bridges, A. J. (2010). Rheumatoid vasculitis: Vanishing menace or target for new treatments? Current Rheumatology Reports, 12(6), 414–419. https://doi.org/10.1007/s11926-010-0130-1

Lassen, J., & Baron, R. (2021). Rheumatische Erkrankungen und neuropathischer Schmerz: Diagnose und Therapie [Rheumatic diseases and neuropathic pain: Diagnosis and treatment]. Zeitschrift für Rheumatologie, 80(3), 226–233. https://doi.org/10.1007/s00393-020-00950-9

Rajeshwari, B., & Kumar, S. (2023, January 24). Rheumatoid neuropathy: A brief overview. Cureus, 15(1), e34127. https://doi.org/10.7759/cureus.34127

Noori, S. A., Aiyer, R., Yu, J., White, R. S., Mehta, N., & Gulati, A. (2019). Nonopioid versus opioid agents for chronic neuropathic pain, rheumatoid arthritis pain, cancer pain and low back pain. Pain Management, 9(2), 205–216. https://doi.org/10.2217/pmt-2018-0052

Derry, S., Wiffen, P. J., Moore, R. A., & Quinlan, J. (2014). Topical lidocaine for neuropathic pain in adults. Cochrane Database of Systematic Reviews, 2014(7), CD010958. https://doi.org/10.1002/14651858.CD010958.pub2

Richards, B. L., Whittle, S. L., & Buchbinder, R. (2012). Neuromodulators for pain management in rheumatoid arthritis. Cochrane Database of Systematic Reviews, 2012(1), CD008921. https://doi.org/10.1002/14651858.CD008921.pub2

Cavalli, E., Mammana, S., Nicoletti, F., Bramanti, P., & Mazzon, E. (2019). The neuropathic pain: An overview of the current treatment and future therapeutic approaches. International Journal of Immunopathology and Pharmacology, 33, 2058738419838383. https://doi.org/10.1177/2058738419838383

Brosseau, L., Judd, M. G., Marchand, S., Robinson, V. A., Tugwell, P., Wells, G., & Yonge, K. (2003). Transcutaneous electrical nerve stimulation (TENS) for the treatment of rheumatoid arthritis in the hand. Cochrane Database of Systematic Reviews, 2003(3), CD004377. https://doi.org/10.1002/14651858.CD004377

Muramatsu, K., Tanaka, H., & Taguchi, T. (2008). Peripheral neuropathies of the forearm and hand in rheumatoid arthritis: Diagnosis and options for treatment. Rheumatology International, 28(10), 951–957. https://doi.org/10.1007/s00296-008-0630-8

Ifesemen, O. S., McWilliams, D. F., Ferguson, E., Wakefield, R., Akin-Akinyosoye, K., Wilson, D., Platts, D., Ledbury, S., & Walsh, D. A. (2021). Central Aspects of Pain in Rheumatoid Arthritis (CAP-RA): Protocol for a prospective observational study. BMC Rheumatology, 5(1), 23. https://doi.org/10.1186/s41927-021-00187-2

Filatova, E., Pogozheva, E., Amirdzhanova, V., et al. (2021). Central sensitization in rheumatoid arthritis (Abstract AB0165). Annals of the Rheumatic Diseases, 80(Suppl 1), 1109.

Mesci, N., Mesci, E., Kandemir, E. U., Kulcu, D. G., & Celik, T. (2024). Impact of central sensitization on clinical parameters in patients with rheumatoid arthritis. Northern Clinics of Istanbul, 11(2), 140–146. https://doi.org/10.14744/nci.2023.81231

Stanislavchuk, M., & Bombela, V. (2024). Assessment of the central sensitization by the central sensitization inventory in patients with rheumatoid arthritis (Abstract AB0149). Annals of the Rheumatic Diseases, 83(Suppl 1), 1309. https://doi.org/10.1136/annrheumdis-2024-eular.5934

Minhas, D., Murphy, A., & Clauw, D. J. (2023). Fibromyalgia and centralized pain in the rheumatoid arthritis patient. Current Opinion in Rheumatology, 35(3), 170–174. https://doi.org/10.1097/BOR.0000000000000929

Reeve, A. J., Patel, S., Fox, A., Walker, K., & Urban, L. (2000). Intrathecally administered endotoxin or cytokines produce allodynia, hyperalgesia and changes in spinal cord neuronal responses to nociceptive stimuli in the rat. European Journal of Pain, 4(3), 247–257. https://doi.org/10.1053/eujp.2000.0177

Schaible, H.-G., von Banchet, G. S., Boettger, M. K., Bräuer, R., Gajda, M., Richter, F., Hensellek, S., Brenn, D., & Natura, G. (2010). The role of proinflammatory cytokines in the generation and maintenance of joint pain. Annals of the New York Academy of Sciences, 1193(1), 60–69. https://doi.org/10.1111/j.1749-6632.2009.05301.x

Cao, Y., Fan, D., & Yin, Y. (2020). Pain mechanism in rheumatoid arthritis: From cytokines to central sensitization. Mediators of Inflammation, 2020, 2076328. https://doi.org/10.1155/2020/2076328

Woolf, C. J. (2011). Central sensitization: Implications for the diagnosis and treatment of pain. Pain, 152(3 Suppl), S2–S15. https://doi.org/10.1016/j.pain.2010.09.030

Kawasaki, Y., Zhang, L., Cheng, J. K., & Ji, R. R. (2008). Cytokine mechanisms of central sensitization: Distinct and overlapping role of interleukin-1β, interleukin-6, and tumor necrosis factor-α in regulating synaptic and neuronal activity in the superficial spinal cord. Journal of Neuroscience, 28(20), 5189–5194. https://doi.org/10.1523/JNEUROSCI.3338-07.2008

Lee, Y. C., Napadow, V., & Loggia, M. L. (2018). Editorial: Functional connectivity: Dissecting the relationship between the brain and “pain centralization” in rheumatoid arthritis. Arthritis & Rheumatology, 70(7), 977–980. https://doi.org/10.1002/art.40454

Buckner, R. L., Andrews-Hanna, J. R., & Schacter, D. L. (2008). The brain’s default network: Anatomy, function, and relevance to disease. Annals of the New York Academy of Sciences, 1124(1), 1–38. https://doi.org/10.1196/annals.1440.011

Basu, N., Kaplan, C. M., Ichesco, E., Larkin, T., Harris, R. E., Murray, A., Waiter, G., & Clauw, D. J. (2018). Neurobiologic features of fibromyalgia are also present among rheumatoid arthritis patients. Arthritis & Rheumatology, 70(7), 1000–1007. https://doi.org/10.1002/art.40451

Khot, S., Tackley, G., & Choy, E. (2024). How to distinguish non-inflammatory from inflammatory pain in RA? Current Rheumatology Reports, 26(12), 403–413. https://doi.org/10.1007/s11926-024-01159-4

Harte, S. E., Harris, R. E., & Clauw, D. J. (2018). The neurobiology of central sensitization. Journal of Applied Behavioral Research, 23(2), e12137. https://doi.org/10.1111/jabr.12137

Dydyk, A. M., Chiebuka, E., & Stretanski, M. F. (2025). Central pain syndrome. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK553027/

Staud, R., Godfrey, M. M., & Robinson, M. E. (2021). Fibromyalgia patients are not only hypersensitive to painful stimuli but also to acoustic stimuli. The Journal of Pain, 22(8), 914–925. https://doi.org/10.1016/j.jpain.2021.02.009

Song, J., Muhammad, L. N., Neogi, T., Dunlop, D. D., Wohlfahrt, A., Bolster, M. B., Bingham, C. O., Clauw, D. J., Marder, W., & Lee, Y. C. (2023). Pain sensitization as a potential mediator of the relationship between sleep disturbance and subsequent pain in rheumatoid arthritis. Arthritis Care & Research, 75(4), 778–784. https://doi.org/10.1002/acr.24888

Giannotta, M., et al. (2024). Impact of mood disorders assessed with DASS-21 (Depression Anxiety Stress Scale) on disease activity in patients with rheumatoid arthritis and fibromyalgia (Abstract AB0143). Annals of the Rheumatic Diseases, 83(Suppl 1), 1306–1307. https://ard.eular.org/article/S0003-4967(24)16829-X/

Dhir, V., Lawrence, A., Aggarwal, A., & Misra, R. (2009). Fibromyalgia is common and adversely affects pain and fatigue perception in North Indian patients with rheumatoid arthritis. The Journal of Rheumatology, 36(11), 2443–2448. https://doi.org/10.3899/jrheum.090157

Weisman, M. H., & Corr, M. (2023). Ból w chorobach reumatycznych (B. Kwiatkowska, Red. wyd. pol.). Edra Urban & Partner. ISBN 9788367447348

Yunus, M. B. (2007). Role of central sensitization in symptoms beyond muscle pain, and the evaluation of a patient with widespread pain. Best Practice & Research Clinical Rheumatology, 21(3), 481–497. https://doi.org/10.1016/j.berh.2007.03.006

Kaplan, C. M., Schrepf, A., Ichesco, E., Larkin, T., Harte, S. E., Harris, R. E., Murray, A. D., Waiter, G. D., Clauw, D. J., & Basu, N. (2020). Association of inflammation with pronociceptive brain connections in rheumatoid arthritis patients with concomitant fibromyalgia. Arthritis & Rheumatology, 72(1), 41–46. https://doi.org/10.1002/art.41069

Barcelon, E., Chung, S., Lee, J., & Lee, S. J. (2023). Sexual dimorphism in the mechanism of pain central sensitization. Cells, 12(16), 2028. https://doi.org/10.3390/cells12162028

Mercante, F. G., Fernandes, G., Braido, G. V. D. V., Proença, J. D. S., Andersen, M. L., Hachul, H., & Gonçalves, D. A. G. (2023). Insomnia is associated with symptoms of central sensitization in patients with painful temporomandibular disorders. Journal of the American Dental Association, 154(11), 1024–1031. https://doi.org/10.1016/j.adaj.2023.02.017

Rifbjerg-Madsen, S., Christensen, A. W., Christensen, R., Hetland, M. L., Bliddal, H., Kristensen, L. E., Danneskiold-Samsøe, B., & Amris, K. (2017). Pain and pain mechanisms in patients with inflammatory arthritis: A Danish nationwide cross-sectional DANBIO registry survey. PLoS ONE, 12(7), e0180014. https://doi.org/10.1371/journal.pone.0180014

Mayer, T. G., Neblett, R., Cohen, H., Howard, K. J., Choi, Y. H., Williams, M. J., Perez, Y., Gatchel, R. J. (2012). The development and psychometric validation of the Central Sensitization Inventory. Pain Practice, 12(4), 276–285. https://doi.org/10.1111/j.1533-2500.2011.00493.x

Kregel, J., Vuijk, P. J., Descheemaeker, F., Keizer, D., van der Noord, R., Nijs, J., Cagnie, B., Meeus, M., & van Wilgen, P. (2016). The Dutch Central Sensitization Inventory (CSI): Factor analysis, discriminative power, and test-retest reliability. Clinical Journal of Pain, 32(7), 624–630. https://doi.org/10.1097/AJP.0000000000000306

Dixon, E. A., Benham, G., Sturgeon, J. A., Mackey, S., Johnson, K. A., & Younger, J. (2016). Development of the Sensory Hypersensitivity Scale (SHS): A self-report tool for assessing sensitivity to sensory stimuli. Journal of Behavioral Medicine, 39(3), 537–550. https://doi.org/10.1007/s10865-016-9720-3

Georgopoulos, V., Smith, S., McWilliams, D. F., Ferguson, E., Wakefield, R., Platts, D., Ledbury, S., Wilson, D., & Walsh, D. A. (2024). Contribution of inflammation markers and quantitative sensory testing (QST) indices of central sensitisation to rheumatoid arthritis pain. Arthritis Research & Therapy, 26(1), 175. https://doi.org/10.1186/s13075-024-03407-5

Altun Güvenir, A., Çalışkan Uçkun, A., Yurdakul, F. G., & Bodur, H. (2025). What does pain sensitivity really predict in rheumatoid arthritis patients? Agri, 37(1), 50–58. https://doi.org/10.14744/agri.2024.30643

Wohlfahrt, A., Muhammad, L. N., Song, J., Dunlop, D. D., Neogi, T., Bingham, C. O., Bolster, M. B., Marder, W., Clauw, D. J., & Lee, Y. C. (2023). Pain mechanisms associated with disease activity in patients with rheumatoid arthritis treated with disease-modifying antirheumatic drugs: A regression tree analysis. Journal of Rheumatology, 50(6), 741–747. https://doi.org/10.3899/jrheum.220500

Riquelme-Aguado, V., González-Álvarez, M. E., Zabarte-Del Campo, A., Fernández-Carnero, J., Gil-Crujera, A., Gómez-Esquer, F., & Villafañe, J. H. (2024). Comparison between conditioned pain modulation paradigms using cold pressor conditioning stimulus versus ischemic pressure stimulus in women with fibromyalgia and its impact on clinical status: A cross-sectional study. Biomedicines, 12(10), 2222. https://doi.org/10.3390/biomedicines12102222

Hwang, Y. G., Zhu, L., Wasan, A., & Moreland, L. W. (2017). Measurement properties of painDETECT, a neuropathic pain screening tool, for evaluating pain phenotype in patients with rheumatoid arthritis: Developing neuropathic pain scale as a measure of treatment outcome by applying Rasch analysis [Abstract]. Arthritis & Rheumatology, 69(suppl 10). https://acrabstracts.org/abstract/measurement-properties-of-paindetect-a-neuropathic-pain-scr eening-tool-for-evaluating-pain-phenotype-in-patients-with-rheumatoid-arthritis-developingneuropathic-pain-scale-as-a-measure-of-treatmen/

Rifbjerg-Madsen, S., Christensen, A. W., Boesen, M., Christensen, R., Danneskiold-Samsøe, B., Bliddal, H., Dreyer, L., Locht, H., & Amris, K. (2018). The course of pain hypersensitivity according to painDETECT in patients with rheumatoid arthritis initiating treatment: Results from the prospective FRAME-cohort study. Arthritis Research & Therapy, 20(1), 105. https://doi.org/10.1186/s13075-018-1581-4

Timmerman, H., Steegers, M. A. H., Huygen, F. J. P. M., Goeman, J. J., van Dasselaar, N. T., Schenkels, M. J., Wilder-Smith, O. H. G., Wolff, A. P., & Vissers, K. C. P. (2017). Investigating the validity of the DN4 in a consecutive population of patients with chronic pain. PLoS ONE, 12(11), e0187961. https://doi.org/10.1371/journal.pone.0187961

Migliore, A., Gigliucci, G., Moretti, A., Pietrella, A., Peresson, M., Atzeni, F., Sarzi-Puttini, P., Bazzichi, L., Liguori, S., & Iolascon, G. (2021). Cross-cultural adaptation and validation of Italian version of the Leeds Assessment of Neuropathic Symptoms and Signs Scale and painDETECT questionnaire for the distinction between nociceptive and neuropathic pain. Pain Research and Management, 2021, 6623651. https://doi.org/10.1155/2021/6623651

Covic, T., Pallant, J. F., Tennant, A., et al. (2009). Variability in depression prevalence in early rheumatoid arthritis: A comparison of the CES-D and HAD-D scales. BMC Musculoskeletal Disorders, 10, 18. https://doi.org/10.1186/1471-2474-10-18

Son, C. N., Choi, G., Lee, S. Y., Lee, J. M., Lee, T. H., Jeong, H. J., Jung, C. G., Kim, J. M., Cho, Y. W., & Kim, S. H. (2015). Sleep quality in rheumatoid arthritis, and its association with disease activity in a Korean population. Korean Journal of Internal Medicine, 30(3), 384–390. https://doi.org/10.3904/kjim.2015.30.3.384

Seror, R., Tubach, F., Baron, G., Guillemin, F., & Ravaud, P. (2010). Measure of function in rheumatoid arthritis: Individualised or classical scales? Annals of the Rheumatic Diseases, 69(1), 97–101. https://doi.org/10.1136/ard.2008.102137

Taylor, W. J., Myers, J., Simpson, R. T., McPherson, K. M., & Weatherall, M. (2004). Quality of life of people with rheumatoid arthritis as measured by the World Health Organization Quality of Life Instrument, short form (WHOQOL-BREF): Score distributions and psychometric properties. Arthritis & Rheumatism, 51(3), 350–357. https://doi.org/10.1002/art.20398

Sandström, A., Ellerbrock, I., Jensen, K. B., Martinsen, S., Altawil, R., Hakeberg, P., Fransson, P., Lampa, J., & Kosek, E. (2019). Altered cerebral pain processing of noxious stimuli from inflamed joints in rheumatoid arthritis: An event-related fMRI study. Brain, Behavior, and Immunity, 81, 272–279. https://doi.org/10.1016/j.bbi.2019.06.024

Thomas, G., Maria, S. G., Udas, G., Kanti, R. B., Apurva, A., Abontika, R., Sandeep, S., Rehana, C., & Colonel, M. V. (2022). Proportion of peripheral neuropathy in newly diagnosed rheumatoid arthritis: A single-centre retrospective observational study. JK Science, 24(2), 89–93.

Rathi, N., Taksande, B., & Kumar, S. (2019). Nerve conduction studies of peripheral motor and sensory nerves in the subjects with prediabetes. Journal of Endocrinology and Metabolism, 9(5), 147–150. https://doi.org/10.14740/jem602

Hui, M., Meena, A. K., Rajasekhar, L., Sireesha, Y., Afshan, J., Mridula, R., Borgohain, R., & Uppin, M. S. (2019). Vasculitic neuropathy: A retrospective analysis of nerve biopsies and clinical features from a single tertiary care center. Annals of Indian Academy of Neurology, 22(2), 180–186. https://doi.org/10.4103/aian.AIAN_47_18

Meeus, M., Ickmans, K., Struyf, F., Hermans, L., Van Noesel, K., Oderkerk, J., Declerck, L. S., Moorkens, G., Hans, G., Grosemans, S., & Nijs, J. (2013). Does acetaminophen activate endogenous pain inhibition in chronic fatigue syndrome/fibromyalgia and rheumatoid arthritis? A double-blind randomized controlled cross-over trial. Pain Physician, 16(2), E61–E70. https://www.painphysicianjournal.com/linkout?issn=&vol=16&page=E61

Sacre, S., Medghalchi, M., Gregory, B., Brennan, F., & Williams, R. (2010). Fluoxetine and citalopram exhibit potent anti-inflammatory activity in human and murine models of rheumatoid arthritis and inhibit toll-like receptors. Arthritis & Rheumatism, 62(3), 683–693. https://doi.org/10.1002/art.27304

Lee, Y. C., Massarotti, E., Edwards, R. R., Lu, B., Liu, C., Lo, Y., Wohlfahrt, A., Kim, N. D., Clauw, D. J., & Solomon, D. H. (2016). Effect of milnacipran on pain in patients with rheumatoid arthritis with widespread pain: A randomized blinded crossover trial. Journal of Rheumatology, 43(1), 38–45. https://doi.org/10.3899/jrheum.150550

Rupp, A., Young, E., & Chadwick, A. L. (2023). Low-dose naltrexone’s utility for non-cancer centralized pain conditions: A scoping review. Pain Medicine, 24(11), 1270–1281. https://doi.org/10.1093/pm/pnad074

Kaye, A. D., Perilloux, D. M., Hawkins, A. M., Wester, G. C., Ragaland, A. R., Hebert, S. V., Kim, J., Heisler, M., Kelkar, R. A., Chami, A. A., Shekoohi, S., & Kaye, A. M. (2024). Tumor necrosis factor and interleukin modulators for pathologic pain states: A narrative review. Pain and Therapy, 13(3), 481–493. https://doi.org/10.1007/s40122-024-00603-8

Hess, A., Axmann, R., Rech, J., Finzel, S., Heindl, C., Kreitz, S., Sergeeva, M., Saake, M., Garcia, M., Kollias, G., Straub, R. H., Sporns, O., Doerfler, A., Brune, K., & Schett, G. (2011). Blockade of TNF-α rapidly inhibits pain responses in the central nervous system. Proceedings of the National Academy of Sciences of the United States of America, 108(9), 3731–3736. https://doi.org/10.1073/pnas.1011774108

Fleischmann, R., van Adelsberg, J., Lin, Y., Castelar-Pinheiro, G. D., Brzezicki, J., Hrycaj, P., Graham, N. M., van Hoogstraten, H., Bauer, D., & Burmester, G. R. (2017). Sarilumab and nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis and inadequate response or intolerance to tumor necrosis factor inhibitors. Arthritis & Rheumatology, 69(2), 277–290. https://doi.org/10.1002/art.39944

Simon, L. S., Taylor, P. C., Choy, E. H., Sebba, A., Quebe, A., Knopp, K. L., & Porreca, F. (2021). The Jak/STAT pathway: A focus on pain in rheumatoid arthritis. Seminars in Arthritis and Rheumatism, 51(1), 278–284. https://doi.org/10.1016/j.semarthrit.2020.10.008

Sarzi-Puttini, P., Zen, M., Arru, F., Giorgi, V., & Choy, E. A. (2023). Residual pain in rheumatoid arthritis: Is it a real problem? Autoimmunity Reviews, 22(11), 103423. https://doi.org/10.1016/j.autrev.2023.103423

Gottrup, H., Juhl, G., Kristensen, A. D., Lai, R., Chizh, B. A., Brown, J., Bach, F. W., & Jensen, T. S. (2004). Chronic oral gabapentin reduces elements of central sensitization in human experimental hyperalgesia. Anesthesiology, 101(6), 1400–1408. https://doi.org/10.1097/00000542-200412000-00021

Cao, Y., Wang, H., Chiang, C. Y., Dostrovsky, J. O., & Sessle, B. J. (2013). Pregabalin suppresses nociceptive behavior and central sensitization in a rat trigeminal neuropathic pain model. Journal of Pain, 14(2), 193–204. https://doi.org/10.1016/j.jpain.2012.11.005

Louw, A., Diener, I., Butler, D. S., & Puentedura, E. J. (2011). The effect of neuroscience education on pain, disability, anxiety, and stress in chronic musculoskeletal pain. Archives of Physical Medicine and Rehabilitation, 92(12), 2041–2056. https://doi.org/10.1016/j.apmr.2011.07.198

Meert, L., Smeets, R. J. E. M., Baert, I., et al. (2019). Treatment of central sensitization in patients with rheumatoid arthritis: A narrative overview. Current Treatment Options in Rheumatology, 5(3), 179–189. https://doi.org/10.1007/s40674-019-00125-x

Vlaeyen, J. W. S., & Linton, S. J. (2000). Fear-avoidance and its consequences in chronic musculoskeletal pain: A state of the art. Pain, 85(3), 317–332. https://doi.org/10.1016/S0304-3959(99)00242-0

Meeus, M., Hermans, L., Ickmans, K., Struyf, F., Van Cauwenbergh, D., Bronckaerts, L., De Clerck, L. S., Moorken, G., Hans, G., Grosemans, S., & Nijs, J. (2015). Endogenous pain modulation in response to exercise in patients with rheumatoid arthritis, patients with chronic fatigue syndrome and comorbid fibromyalgia, and healthy controls: A double-blind randomized controlled trial. Pain Practice, 15(2), 98–106. https://doi.org/10.1111/papr.12181

Simonsen, M. B., Næsborg-Andersen, K., Leutscher, P. D. C., Hørslev-Petersen, K., Woodburn, J., Andersen, M. S., & Hirata, R. P. (2022). The effect of foot orthoses on gait biomechanics and pain among people with rheumatoid arthritis: A quasi-experimental study. Gait & Posture, 95, 121–128. https://doi.org/10.1016/j.gaitpost.2022.04.016