Impact of JAK-inhibition on pain and biphasic P2X7R expression on CD4+ T cells in experimental arthritis

Pain improvement is a major unmet need for patients with rheumatoid arthritis (RA). The purinergic receptor P2 X7R may play a central role in inflammatory pain. We aimed to assess the differential effect of Jak and TNF-α inhibition on pain in a collagen-induced arthritis (CIA) mouse model and to decipher mechanisms, focusing on P2X7R. Either a Jak-inhibitor (baricitinib, BARI) or an anti-TNF-α (etanercept, ETN) were administered to CIA mice in early or late phase of arthritis. Pain was evaluated with three independent tests. We assessed P2X7R on leucocytes and IFN-γ, IL-1β, TNF-α, IL-10, IL-6 and IL-17 A concentrations. BARI and ETN decreased joint inflammation and ameliorated histologic destruction and inflammation. When administered in the late phase, ETN and BARI exerted an analgesic effect. P2X7R expression on blood CD4+ T cells was increased in early phase BARI treated mice, and decreased in late phase. When treatments were administered early, percentage of P2 × 7R+ CD4+ T cells inversely correlated with clinical and histological scores, and with IL-6, IL-17 A and IL-1β levels. In conclusion, both BARI and ETN improved pain in a CIA model. The differential expression of P2X7R on CD4+ T cells according to the time of BARI administration may contribute to a better understanding of pain mechanisms in arthritis.