Understanding the Psychophysiological Mechanisms Related to Widespread Pressure Pain Hyperalgesia Underpinning Carpal Tunnel Syndrome: A Network Analysis Approach

Objective: Current evidence suggests that carpal tunnel syndrome (CTS) involves widespread pressure pain sensitivity as a manifestion of central sensitization. This study aimed to quantify mechanisms driving widespread pressure pain hyperalgesia in CTS by using network analysis. Design: Cross-sectional. Setting: Urban hospital. Subjects: Women with CTS (n=120) who participated in a previous randomized clinical trial. Methods: Pain intensity, related function, symptom severity, depressive levels, and pressure pain threshold (PPTs) over the median, radial, and ulnar nerves, as well as the cervical spine, the carpal tunnel, and the tibialis anterior, were collected. Network analysis was used to quantify the adjusted correlations between the modeled variables and to determine the centrality indices of each variable (i.e., the degree of connection with other symptoms in the network). Results: The estimated network showed several local associations between clinical variables and the psychophysical outcomes separately. The edges with the strongest weights were those between the PPT over the median nerve and the PPT over the radial nerve (P=0.34), between function and depressive levels (P=0.30), and between the PPT over the carpal tunnel and the PPT over the tibialis anterior (P=0.29). The most central variables were PPT over the tibialis anterior (the highest Strength centrality) and PPT over the carpal tunnel (the highest Closeness and Betweenness centrality). Conclusions: This is the first study to apply network analysis to understand the multivariate mechanisms of individuals with CTS. Our findings support a model in which clinical symptoms, depression, and widespread pressure pain sensitivity are connected, albeit within separate clusters. The clinical implications of the present findings, such as the development of treatments targeting these mechanisms, are also discussed.