Resting-state cortical activity, biomarkers and functional performance identify distinct biopsychosocial phenotypes...

Chronic postsurgical pain (CPSP) is a prevalent and disabling condition in young adults (AYAs) yet marked variability in symptoms and functional impact is poorly explained by pain severity alone. This study aimed to (1) compare psychological symptoms, physical performance, hair cortisol concentration, and resting-state cortical hemodynamic activity between AYAs with CPSP and healthy controls; (2) examine associations among these variables within the CPSP group; and (3) derive clinically meaningful CPSP phenotypes anchored in physical performance using hierarchical clustering.

In this cross-sectional study, AYAs aged 18-30 years with CPSP and healthy controls were enrolled. Psychological symptoms and pain interference were assessed using standardized self-report measures. Physical performance was evaluated using the 1 min sit-to-stand test, with concurrent physiological responses to exertion. Resting-state cortical hemodynamic activity was assessed using functional near-infrared spectroscopy (fNIRS).

A total of 67 AYAs (33 with CPSP and 34 healthy controls) were included. Compared with healthy controls, AYAs with CPSP reported significantly greater pain interference and exhibited dysregulated physiological responses to exertion, despite comparable objective physical performance. Within the CPSP group, psychological distress, hair cortisol concentration, physical performance, and resting-state prefrontal and somatosensory cortex (SMC) (S1) activity were significantly interrelated. Clustering analyses identified two distinct CPSP phenotypes, low functioning and high functioning, which differed in pain catastrophizing, autonomic reactivity, and resting state SMC (S1) activity.

CPSP in AYAs is associated with distinct autonomic, neuroendocrine, and cortical signatures that co-vary with functional performance. Integrating physiological biomarkers and resting-state neuroimaging with performance-based assessments may improve mechanistic understanding and phenotyping of CPSP.