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Chronic pain is a major global public health problem and a leading driver of healthcare use and its associated costs. Clinical management remains challenging because chronic pain is multidimensional and requires a patient-centred approach that is consistent with the current biopsychosocial paradigm. Importantly, more than 85% of presentations are labelled "non-specific", highlighting the limited diagnostic yield of conventional imaging for identifying a single pathoanatomical cause. Pain chronification arises from interacting mechanisms spanning molecular, psychological, and social levels, creating an urgent need for high-quality research that refines diagnostic strategies, improves patient stratification, and enables more targeted care. This Special Issue includes the following topics: imaging and neuroimaging; somatosensory profiling (e.g., quantitative sensory testing); clinical prediction and risk models; biomarkers and digital phenotyping; new proposals for clinically meaningful phenotypes or endotypes; evaluations of diagnostic pathways; and demonstrations of how improved classification informs treatment selection, prognosis, and patient-relevant outcomes. The overarching aim is to move beyond the broad—and often unhelpful—category of "non-specific" chronic pain.

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