Evaluation of Pain Sensitization in Rheumatoid Arthritis: Analysis on a Cohort of Tofacitinib Treated Patients

Persistent pain and chronic fatigue are very common complaints in rheumatoid arthritis (RA) patients, whatever the anti-inflammatory treatment response. Interestingly, pain remaining despite good clinical response was associated with high disability and low inflammation at baseline, suggesting a mechanism of pain independent of inflammation in these patients. Such patients, with discordantly high patient-reported DAS28 components, fatigue and mood disturbance might represent a subgroup of RA patients who have specific clinical needs, not resolved by classical conventional or biologic DMARDs. In this way, neuropathic pain and pain sensitization have been demonstrated in 20 to 30% of RA patients, neuropathic pain scores being associated with worsen disease activity scores. Thus, pain sensitization may contribute to amplification of pain in active RA, and should be responsible for persisting pain and fatigue even after inflammation has resolved. Pain sensitization is associated with neuroplastic changes in sensory pathways at peripheral and central levels. Interestingly, major mediators responsible for this neuroplasticity operate via a JAK/STAT signaling pathway, which is specifically targeted by new RA treatments. New drug targeting JAK/STAT signalling pathway have been recently designed for RA treatment, based on the implication of this pathway on the signaling of various cytokines implicated in the pathophysiology of RA, such as IL-6, IL-12, IL-23 and IFNs. Two Jak-inhibitors have been put on the market: Tofacitinib and Baricitinib. In randomized clinical trials, Tofacitinib have shown a remarkable efficacy on pain and other patient reported outcomes, suggesting a specific effect or jak-inhibitors on pain control. Recent data suggest that Jak-inhibitors could have a direct effect on sensory neurons.