DISCOVERY OF NOVEL TARGETS IN A CRPS MOUSE MODEL BY TRANSCRIPTOMICS: TNF AND JAK-STAT PATHWAYS. NOVEL TARGETS IN A CRPS MOUSE MODEL BY TRANSCRIPTOMICS

Complex Regional Pain Syndrome (CRPS) represents severe chronic pain, hypersensitivity, and inflammation induced by complex sensory-immune-vascular interactions after a small injury. Since the therapy is unsatisfactory, novel drug targets are needed. Unbiased transcriptomic analysis of the dorsal root ganglia (DRG) was performed in a passive transfer-trauma mouse model followed by pharmacological confirmation of discovered pathways.In the unilateral L4-6 DRG samples 125 genes were differentially expressed in response to plantar incision and IgG injection of CRPS patients. These are related to inflammatory and immune responses, cytokines, chemokines and neuropeptides. Pathway analysis revealed involvement of TNF and JAK-STAT signalling. This was confirmed by abolished CRPS IgG-induced increased hyperalgesia by the soluble TNF alpha receptor etanercept and the JAK-STAT inhibitor tofacitinib. They reduced microglia and astrocyte markers in pain-associated brain regions. This is the first evidence for CRPS-related cytokine signalling in the DRGs suggesting therapeutic potentials of etanercept and tofacitinib, that have long been used in autoimmune diseases such as arthritis.