Publications

Many cytokines associated with RA pathogenesis and pain are affected directly or indirectly by the JAK/STAT pathway, therapeutic targeting may offer promise. Having better understanding of these mechanisms can help clinicians make treatment decisions that optimise the control of inflammation and pain. However, pain in patients with RA is complex and involves multiple driving mechanisms that may differentially occur over time in different people. Although one known constant is that nociceptive activation almost always promotes pain, even when joint inflammation is limited. Approaches that can normalise the threshold for activation of nociceptors or diminish central transmission would therefore be desirable for RA patients.This descriptive review summarises the involvement of the JAK/STAT pathway in mediating the action, expression, and regulation of a multitude of pro- and anti-inflammatory cytokines, and examines the mechanisms contributing to pain in RA. The evidence to date suggests that activation of the JAK/STAT signalling pathway can either diminish or intensify pain depending on the intracellular mechanisms activated. The precise contribution to nociception is not yet well understood; however, multiple cytokine receptors are expressed on afferent nociceptors, and cytokines acting at these receptors have been implicated in pain modulation. Given recent clinical trial results, this review postulates that patients who achieve a measured clinical response to a given treatment, but are not developing satisfactory improvement in pain, might derive additional benefit from switching to or incorporating a treatment targeting the Jak/STAT pathway.