Pain is the main disabling symptom in arthritis. Inflammation and tissue damage cause nociceptive pain, which normally improves with injury healing and disease control. Many patients develop nociplastic pain, which persists in the absence of inflammation and tissue damage. It was discovered that, in mice, ablating Nav1.8-expressing nociceptors preserves nociceptive pain but prevents the establishment of nociplastic pain. Whilst ablating neuronal populations is not a viable option in patients, these data demonstrate that specifically targeting nociplastic pain is possible. By comparing the transcriptome of patients with prevalently nociceptive versus prevalently nociplastic pain from highly characterized prospective cohorts and cross-referencing with transcriptomics data in animal models of rheumatoid arthritis, osteoarthritis and nociplastic pain, the group will identify transcripts associated with the development of nociplastic pain. After an in-silico analysis to predict and prioritize key molecular players amenable for targeting, the group will use gain- and loss-of-function experiments in animal models to determine which of these genes/pathways are essential for the transition from nociceptive to nociplastic pain.