Figure 1.

Central and peripheral mechanisms involving macrophages and glial cells contribute to the development of pain in RA. Imbalance between homeostatic TRM and infiltrating macrophages with pro-inflammatory profiles to the synovial tissue contribute to the inflammatory milieu perpetuating inflammation, tissue damage, and bone remodeling affecting nociceptors in the joint. In the DRG, increased proinflammatory macrophages and reduced anti-inflammatory homeostatic/resident-like macrophages contribute to release of pro-inflammatory cytokines and together with satellite glia-induced release of neuromodulation molecules there is an increase in DRG neuronal activity. At the spinal cord increased microglial and astrocyte reactivity also enhance production of pro-inflammatory cytokines and in the brain increased glial reactivity in a region-specific manner regulating cytokine release and GABA neurotransmitter tone affects pain perception in arthritis. Figure created with Biorender.com. Mφ, macrophages; TMR, tissue-resident macrophages.