Mechanisms of chronic pain and clinical aspects of pain in patients with rheumatoid arthritis

Czech version

Authors: J. Šidáková ¹; V. Bernhauerová ²; J. Tomš ¹; T. Soukup ¹
Authors‘ workplace: Subkatedra revmatologie, II. interní gastroenterologická klinika Lékařské fakulty Univerzity Karlovy a Fakultní, nemocnice v Hradci Králové ¹; Katedra biofyziky a fyzikální chemie, Farmaceutická fakulta v Hradci Králové ²
Published in: Čes. Revmatol., 32, 2024, No. 2, p. 57-66.
Category:

Overview

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting up to 1% of the population, and has been shown to impair quality of life. Pain is usually identified as the main limiting symptom for patients, it can be present all the time, and relief from it is rated as the highest priority in improving health and quality of life. Pain in RA is complex, caused by multiple mechanisms, and can be both nociceptive and neuropathic in nature.

Nociceptive pain, which is predominant in RA, is caused by peripheral sensitization (increased sensitivity of peripheral nerves) acting on peripheral nerve endings that are irritated by local agents (inflammatory cytokines and other mediators) produced by immune cells and cells of the damaged tissue at the site of inflammation. These agents include prostaglandins (especially prostaglandin E2), interleukin-1, interleukin-6, and both type 1 and type 2 cyclooxygenase. Potassium, bradykinin, and serotonin also have a direct effect on free nerve endings. These effects lead to irritation of nociceptors, which release substance P and other neuropeptides that cause mast cell degranulation and histamine release. Substance P also affects vasodilation of the surrounding capillaries, the development of edema, and the release of other bradykinin molecules. As a result of this mechanism, intracellular signaling pathways and phosphorylation cascades are activated.

Apart from peripheral sensitization, RA also involves central sensitization, i.e. increased sensitivity of nociceptive neurons of the central nervous system to normal or subliminal stimuli. The result is persistent pain and increased sensitivity to pain even in areas outside the affected joint, distal or remote. This mechanism is also involved in the development of fibromyalgia, which occurs in up to 20% of RA patients.

This review discusses the clinical aspects of pain in RA and current treatment options.

Keywords:

chronic pain – Fatigue – rheumatoid arthritis – depression – analgetics

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