Cytological taxonomy of chronic pain in rheumatoid arthritis: A brief descriptive review

Chronic pain is the main manifestation of rheumatoid arthritis (RA), determining the severity of suffering and functional impairment. Although pain in RA is primarily associated with autoimmune inflammation, it can persist against the background of low activity and even remission of the disease. This makes it necessary to search for the causes and peculiarities of the development of chronic pain in RA. It seems that the classification of pain types in RA can help in personalizing approaches to its medication control. In this regard, the evaluation of the relationship between pain and the cellular composition (pathotype) of synovitis in RA is of great interest. Three main pathotypes are known: lymphoid (with predominance of T and B lymphocytes, plasmocytes), myeloid or diffuse-myeloid (with predominance of macrophages, monocytes, granulocytes) and pauci-immune (mainly consisting of fibroblast-like synoviocytes (FLS)). The lymphoid pathotype is characterised by high positivity for rheumatoid factor and anti-citrullinated protein antibodies, severe RA activity and intense pain, including that associated with polyneuropathy and dysfunctional disorders; the myeloid pathotype is characterized by less severe activity and local nociceptive pain; the pauci-immune pathotype is characterized by moderately severe pain and peripheral hyperalgesia against a background of moderate/low disease activity. The last pathotype can determine chronic pain in seronegative RA and at late stages of the disease, in which marked structural changes are noted. Currently, there is no clear view on drug approaches for the different pathotypes of synovitis in RA. There is limited evidence for the use of CD20 inhibitors (rituximab) and interleukin (IL) 6 inhibitors in the lymphoid pathotype, and IL-6 and tumour necrosis factor α inhibitors in the myeloid pathotype. Currently, active development of drugs to target FLS is underway. The data of some studies indicate higher efficacy of IL-6 inhibitors in pauci-immune pathotype.