Pain Mechanism in Rheumatoid Arthritis: From Cytokines to Central Sensitization

Abstract

Pain is the most common symptom in patients with rheumatoid arthritis (RA). Although in recent years, through the implementation of targeted treatment and the introduction of disease-modifying antirheumatic drugs (DMARDs), the treatment of RA patients has made a significant progress, a large proportion of patients still feel pain. Finding appropriate treatment to alleviate the pain is very important for RA patients. Current research showed that, in addition to inflammation, RA pain involves peripheral sensitization and abnormalities in the central nervous system (CNS) pain regulatory mechanisms. This review summarized the literature on pain mechanisms of RA published in recent years. A better understanding of pain mechanisms will help to develop new analgesic targets and deploy new and existing therapies.

Central Sensitization in Chronic Low Back Pain: A Population-Based Study of a Japanese Mountain Village

“…4 It has been recognized that CS is associated with mechanical hyperalgesia and allodynia in patients with chronic pain conditions. 5 CS has been proposed as an underlying mechanism of musculoskeletal disorders including LBP, [6][7][8] osteoarthritis, [9][10][11] rheumatoid arthritis, 12 neck and shoulder pain, 13 fibromyalgia, 11 and tendinopathies. 14 The Central Sensitization Inventory (CSI) assesses 25 health-related symptom dimensions that have been reported to be associated with CS-related disorders; 15 it is now used as a screening instrument to identify patients whose symptoms are related to CS.…”

“… 4 It has been recognized that CS is associated with mechanical hyperalgesia and allodynia in patients with chronic pain conditions. 5 CS has been proposed as an underlying mechanism of musculoskeletal disorders including LBP, 6–8 osteoarthritis, 9–11 rheumatoid arthritis, 12 neck and shoulder pain, 13 fibromyalgia, 11 and tendinopathies. 14 …”

Outcomes of a Comprehensive Pain Rehabilitation Program for Patients With Fibromyalgia

“…25 Central sensitization syndrome is a neurophysiologic condition that increases neuroexcitability of dorsal horn neurons by increased synaptic transmission and reduces inhibition, 26 in which specific brain areas, the periaqueductal gray matter and the rostral ventromedial medulla, play a critical role. 27 Functional, structural, and chemical changes in the central nervous system 28 eventually modify the sensory, emotional, and modulatory circuits that normally inhibit pain, 29 which underlies increased pain sensitivity associated with hyperalgesia and/or allodynia. 27,30 Polypharmacy is common in the chronic pain population 31 as a consequence of these patients' chronic condition and frequent comorbidities.…”

“…27 Functional, structural, and chemical changes in the central nervous system 28 eventually modify the sensory, emotional, and modulatory circuits that normally inhibit pain, 29 which underlies increased pain sensitivity associated with hyperalgesia and/or allodynia. 27,30 Polypharmacy is common in the chronic pain population 31 as a consequence of these patients' chronic condition and frequent comorbidities. Patients are prescribed several medications and take numerous over-thecounter drugs and supplements.…”

miR-544-3p mediates arthritis pain through regulation of FcγRI

“…Rheumatoid arthritis (RA) is a common chronic autoimmune disease with high morbidity and mortality that primarily affects joints 1 . Joint pain is a cardinal clinical feature of RA that significantly impacts quality of life 2 . Although RA pain is often thought to be of inflammatory origin, pain outcomes in RA can be poor despite optimal control of inflammation with current biologic therapies 3 .…”