Pain in Rheumatoid Arthritis

It is not known whether Food and Drug Administration (FDA)–approved medications for fibromyalgia, such as duloxetine, milnacipran, and pregabalin, are effective in treating pain in RA. Duloxetine and milnacipran are serotonin–norepinephrine reuptake inhibitors and likely work through the inhibitory descending serotonin–norepinephrine pathways. Pregabalin binds to calcium channels, preventing the release of neurotransmitters, including serotonin, norepinephrine, and glutamate. These medications are effective in a variety of other musculoskeletal pain conditions, and duloxetine recently received FDA approval for the treatment of chronic pain due to osteoarthritis and low back pain. If RA patients have a component of central pain, these medications should theoretically be efficacious adjunctive treatments for pain. However, most studies of these medications have specifically excluded patients with systemic inflammatory diseases including RA.

Future Directions

Although rheumatologists have become adept at controlling inflammation with disease-modifying drugs and biologic agents, pain continues to plague a substantial proportion of our patients. The next decade will be an important time for the development of pain research in rheumatology. The ACR has recognized the need for more education and research involving pain and pain management, and the report of the ACR Pain Management Task Force shows just how far we still have to go.²⁰ It is time for clinicians and researchers to acknowledge pain as both a clinical and research priority. Pain in RA should no longer be lost in the shadow of inflammation but rather be seen as an important entity in and of itself.

Dr. Lee is an instructor in medicine, Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, in Boston. Dr. Hassett is an associate research scientist, Department of Anesthesiology, University of Michigan Medical School, Chronic Pain and Fatigue Research Center, in Ann Arbor, Mich.

References

1. Taylor P, Manger B, Alvaro-Gracia J, et al. Patient perceptions concerning pain management in the treatment of rheumatoid arthritis. J Int Med Res. 2010;38:1213-1224.
2. Borenstein D, Altman R, Bello A, et al. Report of the American College of Rheumatology Pain Management Task Force. Arthritis Care Res. 2010;62:590-599.
3. Woolf CJ. What is this thing called pain? J Clin Invest. 2010;120:3742-3744.
4. Geisser ME, Casey KL, Brucksch CB, Ribbens CM, Appleton BB, Crofford LJ. Perception of noxious and innocuous heat stimulation among healthy women and women with fibromyalgia: Association with mood, somatic focus, and catastrophizing. Pain. 2003;102:243-250.
5. Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 2002;46:1333-1343.
6. Ranzolin A, Brenol JC, Bredemeier M, et al. Association of concomitant fibromyalgia with worse disease activity score in 28 joints, health assessment questionnaire, and short form 36 scores in patients with rheumatoid arthritis. Arthritis Rheum. 2009;61:794-800.
7. Coster L, Kendall S, Gerdle B, Henriksson C, Henriksson KG, Bengtsson A. Chronic widespread musculoskeletal pain: A comparison of those who meet criteria for fibromyalgia and those who do not. Eur J Pain. 2008;12:600-610.
8. Wolfe F, Hauser W, Hassett AL, Katz RS, Walitt BT. The development of fibromyalgia – I: Examination of rates and predictors in patients with rheumatoid arthritis (RA). Pain. 2011;152:291-299.
9. Gerecz-Simon EM, Tunks ER, Heale JA, Kean WF, Buchanan WW. Measurement of pain threshold in patients with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and healthy controls. Clin Rheumatol. 1989;8:467-474.
10. Lee YC, Chibnik LB, Lu B, et al. The relationship between disease activity, sleep, psychiatric distress and pain sensitivity in rheumatoid arthritis: A cross-sectional study. Arthritis Res Ther. 2009;11:R160.
11. Leffler AS, Kosek E, Lerndal T, Nordmark B, Hansson P. Somatosensory perception and function of diffuse noxious inhibitory controls (DNIC) in patients suffering from rheumatoid arthritis. Eur J Pain. 2002;6:161-176.
12. Wolfe F, Clauw DJ, Fitzcharles MA, et al. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: A modification of the ACR preliminary diagnostic criteria for fibromyalgia. J Rheumatol. 2011;38:1113-1122.
13. Wolfe F, Clauw DJ, Fitzcharles MA, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res. 2010;62:600-610.
14. Hassett AL, Gevirtz RN. Nonpharmacologic treatment for fibromyalgia: Patient education, cognitive-behavioral therapy, relaxation techniques, and complementary and alternative medicine. Rheum Dis Clin North Am. 2009;35:393-407.
15. Iversen MD, Hammond A, Betteridge N. Self-management of rheumatic diseases: State of the art and future perspectives. Ann Rheum Dis. 2010;69:955-963.
16. Keefe FJ, Somers TJ. Psychological approaches to understanding and treating arthritis pain. Nature Rev. 2010;6:210-216.
17. Cairns AP, McVeigh JG. A systematic review of the effects of dynamic exercise in rheumatoid arthritis. Rheumatol Int. 2009;30:147-158.
18. Hauser W, Klose P, Langhorst J, et al. Efficacy of different types of aerobic exercise in fibromyalgia syndrome: A systematic review and meta-analysis of randomised controlled trials. Arthritis Res Ther. 2010;12:R79.
19. Ash G, Dickens CM, Creed FH, Jayson MI, Tomenson B. The effects of dothiepin on subjects with rheumatoid arthritis and depression. Rheumatology (Oxford). 1999;38:959-967.
20. 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;13:211.