Sensory nerve desensitisation exerts differential effects on the severity of acute pancreatitis in rodent models.

Acute pancreatitis (AP) is a common gastroenterological disorder characterized by severe abdominal pain and inflammation. Despite its high mortality rate, the pathomechanism of AP remains incompletely understood, although neurogenic inflammation - where nerve-derived mediators trigger or amplify inflammatory responses - also appears to contribute to its pathogenesis. The aim of this study was to further investigate the role of neurogenic inflammation in AP and the impact of sensory nerve desensitisation on disease severity. Sensory afferent neurons were ablated using resiniferatoxin (RTX) prior to AP induction in four distinct rat and mouse models. Additionally, TRPV1 knock-out mice were employed to assess the contribution of this ion channel to AP development. Our findings reveal that RTX-induced sensory nerve desensitisation exacerbates the severity of necrotising AP induced by L-ornithine (L-Orn) and sodium taurocholate (NaTc) in rats, as evidenced by increased tissue damage, leukocyte infiltration or serum amylase activity. Conversely, in the cerulein (Cer)-induced oedematous AP rat model, RTX treatment significantly reduced leukocyte infiltration without affecting tissue oedema. In mice, RTX administration worsened the severity of Cer-induced AP, while TRPV1 gene deletion led to a modest reduction in disease severity. These results suggest that the impact of sensory nerve disruption on AP varies depending on the model and type of AP. The study underscores the important role of sensory neurons and TRPV1 ion channels in the pathogenesis and progression of AP, highlighting the potential for targeted therapies that modulate neurogenic inflammation.