Non-inflammatory Causes of Pain in Patients with Rheumatoid Arthritis

Abstract

Although pain in rheumatoid arthritis (RA) is frequently thought to be inflammatory in nature, the association between measures of inflammation and pain intensity is low. This observation is likely due to the multifactorial nature of pain. In addition to pain from joint inflammation, RA patients may also have pain due to structural damage or central etiologies, such as aberrancies in the central nervous system (CNS) pain regulatory pathways. These CNS pathways include mechanisms that facilitate pain, as well as mechanisms that inhibit pain. Other factors, such as sleep disturbances, depression, anxiety, and catastrophizing, may also impact the perception of pain in RA patients. Since pain is frequently used as a proxy for inflammation in the assessment of RA disease activity, it is important that patients and physicians recognize that not all pain is inflammatory, and alternative management strategies, other than escalating disease-modifying antirheumatic drug treatment, may need to be considered.

Discordance between tender and swollen joint count as well as patient's and evaluator's global assessment may reduce likelihood of remission in patients with rheumatoid arthritis and psoriatic arthritis: data from the prospective multicentre NOR-DMARD study

“…Tender joint count and patient's global assessment may both be influenced by pain 5. Level of pain is found to be multifactorial and may be influenced by adverse life events, psychosocial factors, sleep disturbances, dispositional optimism and other personality traits 7 8…”

“…Discordance between subjectively and objectively influenced measures of inflammation may reflect non-inflammatory factors that impact pain, which in turn may lead to misinterpretation of disease activity 5. According to Pollard et al ,19 elevated ΔTSJ may identify patients with fibromyalgic RA, for whom evaluation of disease activity only with DAS28 may cause misclassification.…”

“…Several studies have reported low association between pain and objective measures of inflammation 5. Chronification of pain and development of central sensitisation and conditioned pain modulation can lead to disconnection between tender and swollen joint count, which may be challenging for disease evaluation and treatment 5 6. Psychosocial factors and adverse life events may play a role in triggering sensitisation and chronic multisite musculoskeletal pain 7.…”

Do depression and anxiety reduce the likelihood of remission in rheumatoid arthritis and psoriatic arthritis? Data from the prospective multicentre NOR-DMARD study

“…Continuous measures were compared using Mann-Whitney U-test or independent t-test as appropriate. Proportions were analysed using X2 test.…”

Brain Stimulation Differentially Modulates Nociception and Inflammation in Aversive and Non-aversive Behavioral Conditions

“…Chronic pain is one of the most common disabling factors contributing to cognitive impairments, morbidity, and mortality in multiple clinical disorders including arthritis (Hewlett et al, 2011; Upchurch and Kay, 2012; Boyden et al, 2016; Castañeda et al, 2016). The best current treatments for arthritis are based on disease-modifying anti-rheumatic drugs (DMARDs) that neutralize inflammatory cytokines such as tumor necrosis factor (TNF) and thereby reduce inflammation and leucocytes activation (Ramiro et al, 2011; Upchurch and Kay, 2012).…”