Neural variability reliably encodes interindividual differences in the perception of pain intensity.

Neural activity varies dramatically across time. While such neural variability has been associated with cognition, its relationship with pain remains largely unexplored. Here, we systematically investigated the relationship between neural variability and pain, particularly individual differences in pain intensity discriminability, in six large electroencephalography (EEG) datasets (total N = 633), where healthy volunteers (Datasets 1-5; N = 606) and postherpetic neuralgia patients (Dataset 6; N = 27) received painful or nonpainful sensory stimuli. We found robust correlations between neural variability and interindividual pain intensity discriminability. These correlations were replicable in multiple datasets and seemed not to be caused by stimulus-general factors, as no significant correlations were observed in nonpain modalities. Importantly, variability and amplitude of EEG responses were mutually independent and had distinct temporal and oscillatory profiles in encoding pain intensity discriminability. These findings demonstrate that neural variability is a replicable and potentially preferential indicator of individual differences in pain intensity discriminability, thereby enhancing the understanding of neural encoding of pain intensity discriminability and underscoring the value of neural variability in pain studies.