Differentiating network structures and sex differences of pain-related outcomes, analgesic opioid dosages, and psychosocial factors for postoperative management: a study of PAIN OUT registry in seven Asian regions

Background
Despite advancements in global healthcare, Asia lacks a systematic framework for postoperative pain-related symptoms, particularly in addressing pain identification/prevention and reporting sex differences. This study used network analysis to unravel the complex interplay of pain-related symptoms, analgesic opioid dosages, and psychosocial factors, with a particular focus on sex differences in the Asian population.

Methods
Utilizing anonymized data from 5,093 adult patients across seven Asian regions between 2018 and 2021 from the PAIN OUT registry, this study applied network analysis: 1) to map the relationships between analgesic opioid dosages and multidimensional pain-related symptoms and 2) to explore sex differences. This network analysis was performed based on information from the International Pain Outcomes Questionnaire (IPO-Q), which included pain severity, adverse events, perceptions of pain care perception, and pain treatment satisfaction within 24h of an operation. The model utilized Least Absolute Shrinkage and Selection Operator (LASSO) for regularization and edge estimation, a penalized estimation method allowing for the identification of the most relevant connections while effectively controlling for overfitting.

Results
Network structures demonstrated high stability, revealing distinct sex-based patterns. Chronicity of pain (#CP) emerged as the most central node in the overall network structure (EI = 1.50) and among male patients (EI = 1.80), reflecting the profound effect of persistent pain on their functional activities and sensory-focused symptoms, such as dizziness (#AE4). In contrast, helplessness (#MH2) was a significant symptom in female patients (EI = 1.70), highlighting the emotional and psychological dimensions of their pain experience. Comparative analysis uncovered significant structural differences between males and females (M = 0.154, p = 0.023), emphasizing the unique interplay of psychological, emotional, societal, and pathophysiological symptoms in shaping postoperative pain experiences.

Conclusions
This study was the first comprehensive network analysis of pain-related symptoms with sex differences. The results highlighted a significant difference in associations between analgesic opioid dosages and multidimensional pain-related symptoms among males and females, implying the necessity for region-specific, multimodal interventions to optimize postoperative care in Asian populations.
© The Author(s) 2025