Depression Enhances Visceral Pain and Alters Behavioral Patterns in Chronic Pancreatitis Mice: An Objective Evaluation

Chronic pancreatitis (CP) is frequently associated with persistent visceral pain, which significantly impairs patients' quality of life. Depression, a prevalent comorbidity of chronic visceral pain, has been implicated as a potential risk factor of visceral hyperalgesia in previous clinical studies. However, animal studies that quantitatively and objectively investigated the impact of depression on visceral pain are scarce. In this study, a mice CP model was established via repeated administration of cerulein combined with ethanol, whereas a depressive phenotype was induced through chronic restraint stress (CRS). The concurrent manifestation of depression and CP was achieved by integrating CP modeling and CRS procedure in the same mice. Evaluations using conventional visceral pain metrics demonstrated that depression exacerbated visceral nociception in mice with CP. Through a three-dimensional (3D) video-based analysis of spontaneous behaviors and automated clustering, the CPCRS group exhibited significantly more pronounced visceral pain-related behavioral alterations than the CP group. Furthermore, specific behavioral motifs associated with visceral pain were identified; Grooming and Hunching were intensified by visceral pain, whereas step, running, and left-turn were hindered by CP-induced visceral pain. Overall, this study not only verified the role of depression in visceral pain hypersensitivity in mice but also revealed some previously unreported behavioral patterns linked to visceral pain.