Figure 2.

Treatments that target peripheral and central mechanisms involving macrophages and glial cells for the control of neuroinflammation and pain in RA. In The periphery, targeting TNF with antibodies such as ADA and anti-inflammatory cytokine administration like IL-10 have reduced the release of pro-inflammatory cytokines and reduce polarization of macrophages in the synovium to an M1 phenotype and, in contrast favor polarization to the anti-inflammatory M2 profile. Different inhibitors of JAK kinases and treatments with IL-37 and IL-38 have been reported to increase anti-inflammatory Omega-3 and PUFAs and reduce cytokine release and inflammatory response. Centrally, evidence in arthritic models suggests articular joint movement and environment can affect glial reactivity as well as alpha 2-AR agonist, gabapentin, propofol, and electroacupuncture. Pro-resolving lipids and lipid-lowering agents have been shown to inhibit glial increased reactivity inflammatory response and produce analgesia. And in models different from arthritis, DMARDs have been shown to have an effect in microglia, targeting inflammatory mechanisms described for these cells in the spinal cords and brains of mice models of arthritis. Figure created with Biorender.com. ADA, adalimumab; AJM, articular joint movement; EE, environment enrichment; Mar1, maresin-1; DHA, docosahexaenoic acid.