Neural and psychosocial signatures of the comorbidity between pain and affective symptoms

Pain Rep. 2025 Dec 12;11(1):e1353. doi: 10.1097/PR9.0000000000001353. eCollection 2026 Feb.

ABSTRACT

INTRODUCTION: The bidirectional relationship between pain and affective symptoms suggests shared underlying mechanisms. Neurophysiological changes, psychosocial factors, and specifically alterations in instrumental learning likely contribute significantly to their co-occurrence.

OBJECTIVES: In this study, we aimed to uncover factors associated with the comorbidity between pain and the severity of depressive symptoms and between pain and the severity of anxiety symptoms.

METHODS: We analyzed psychosocial (n = 624) and neuroimaging (n = 689) data from a European sample of young adults with pain and affective symptoms from the general population. Using multitask learning, we constructed cross-sectional models predicting the coexistence of both symptom domains.

RESULTS: Based on blood-oxygen-level-dependent responses during reward feedback, we found a neural pattern associated with the comorbidity between pain and the severity of depressive symptoms, reflecting regionally heterogeneous alterations in reward responsivity. These alterations included stronger negative responses in the caudate nucleus and putamen. In addition, we identified robust psychosocial markers of the comorbidity between pain and the severity of either depressive or anxiety symptoms, among which nonpainful somatic symptoms and persistent rumination showed the most robust association. We further compared the predictive capabilities of psychosocial markers with those of neural processes in instrumental learning and found that neural signatures of reward feedback improved the prediction of a psychosocial signature for the comorbidity between pain and the severity of depressive symptoms.

CONCLUSION: These findings highlight the presence of common mechanisms underlying the comorbidity of pain and affective symptoms, including alterations in the neural responses to reward.

PMID:41404365 | PMC:PMC12705059 | DOI:10.1097/PR9.0000000000001353