Inflammatory-associated apoptotic markers: are they the culprit to rheumatoid arthritis pain?

Rheumatoid arthritis (RA) is a prolonged inflammatory disease resulting from autoimmune reactions that leads to local and systemic bone erosion, joint defects and functional impairment. Although the inflammation is subsided through the prescription of anti-inflammatory therapeutics, the patients persistently complained of sleepless nights due to flare pain. This indicates the possible contribution of other pathways besides inflammation in leading to RA pain. This review aims to uncover the roles and involvement of several inflammatory-associated apoptotic markers in facilitating pain transmission and processing during the pathogenesis of RA.

This narrative review focused on the reports from the previous literature based on the search string of "apoptotic marker AND inflammation AND 'chronic pain' OR 'neuropathic pain' and apoptosis AND 'rheumatoid arthritis' OR arthritis from the databases including Science Direct and Scopus, considering the exclusion criteria of the published abstracts, proceedings or articles on other neuropathic pain types such as painful bowel syndrom, insterstitial cystitis, fibrosis and so on.

Several studies in the literature demonstrate a close association between imbalanced apoptotic regulations and an increased number of synovial fibroblasts and inflammatory cells in RA. Cell death or specific cell survival has been linked with increased central hypersensitivity in various types of chronic and neuropathic pain.

The RA-related flare pain is possibly contributed by the abnormal regulation of apoptosis through several inflammatory-related pathways, and further studies need to modulate these pathways for the putative anti-nociceptive benefits.