Pro-inflammatory cytokines play a key role in the pathogenesis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), and their inhibition is effective in treating these conditions. JAK inhibitors, such as tofacitinib and baricitinib, target the JAK-STAT pathway and have proven efficacy in RA and PsA by affecting multiple cytokines involved in disease development and progression. In addition to their impact on inflammation, cytokines also influence pain and nociception, with increasing attention given to the JAK/STAT pathway’s role in modulating nociceptive responses. Inhibition of this pathway using specific JAK inhibitors holds potential for alleviating pain in these diseases.

Clinical trials and real-world data demonstrate that JAK inhibitors, including tofacitinib and baricitinib, provide rapid pain relief in RA and PsA, suggesting a dual therapeutic role of these drugs in modulating both inflammation and nociception. This review explores the role of pain in rheumatic diseases, the physiological basis for modulating nociceptive pain, and how cytokines and the JAK/STAT pathway contribute to pain mediation. It also summarizes clinical data on the pain-modulating effects of JAK inhibitors in treating RA and PsA, highlighting their potential to improve clinical outcomes by reducing pain beyond the inflammatory component.

Reference: Crispino N, Ciccia F. JAK/STAT pathway and nociceptive cytokine signalling in rheumatoid arthritis and psoriatic arthritis. Clin Exp Rheumatol. 2021 May;39(3):668-675. doi: 10.55563/clinexprheumatol/e7ayu8. PMID: 33200731.