BACKGROUND: Chronic primary pain describes conditions where pain is the principal problem rather than a consequence of another disease. Primary pain is thought to be primarily owing to nociplastic pain (i.e. pain as a result of altered nociception despite the absence of tissue damage). Primary pain is often accompanied by other bothersome central nervous system (CNS)-driven symptoms, including disturbed sleep, mood, and cognition; however, it is unclear whether these symptoms precede onset of primary pain. METHODS: In a prospective cohort study of the UK Biobank, we examined adults with no self-reported recent or chronic pain at baseline. Using linked primary care record data, we investigated the association between the number of CNS-driven symptoms and subsequent incidence of primary pain conditions. Multivariable regression analyses adjusted for sociodemographic and lifestyle factors. RESULTS: Of 502 369 participants, 70 630 (14.0%) met the inclusion criteria, with a mean (range) age of 56.7 (40-70) yr, 51% being female. After 7.4 (range 0.5-11.02) yr, 12.2% developed a primary pain condition. We observed a positive relationship between the number of CNS-driven symptoms at baseline and risk of future primary pain (HR 1.43, 95% CI 1.34-1.52, P<0.001). Participants with more CNS-driven symptoms at baseline were also more likely to have chronic and more severe nociplastic pain, but not non-nociplastic pain at follow-up. CONCLUSIONS: In adults with no current self-reported pain, those with a greater number of CNS-driven symptoms at baseline were more likely to develop a primary pain condition. This suggests a potential opportunity for early intervention in mitigating the burden of primary pain.