LIF is a pro-algesic mediator in human and mouse models of arthritis-related pain

Recent research has uncovered that LIF, a cytokine, plays a significant role in pain associated with arthritis. In their study, scientists examined JAK inhibitors, a type of drug shown to reduce pain in Rheumatoid Arthritis (RA), and discovered that JAK/STAT signalling cytokines such as IL-6, LIF and IL-11 are present in painful RA joints. Among these, LIF emerged as the most impactful, affecting neuronal signaling, growth, and pain-related behaviors in both lab and animal models of arthritis.

To examine this, researchers used human iPSC-derived sensory neurons, which they stimulated with RA synovial fluid (SF) or with cytokine-treated synovial fibroblast conditioned media (CM). They observed that LIF led to increased phosphorylation of STAT3 (pSTAT3) and STAT1 (pSTAT1), as well as changes in the expression of genes linked to pain. These findings were confirmed by RNA sequencing.

Further experiments were conducted using a mouse model of arthritis. The study found that LIF was significantly elevated in the affected joints of these mice and that intravenous injection of LIF into a healthy mouse's knee increased the animal's sensitivity to painful stimuli in that joint.

Overall, these findings suggest that LIF could potentially serve as a pro-algesic mediator, a substance that promotes pain, and could serve as a target for treatments aimed at alleviating pain in individuals with inflammatory arthritis.