OBJECTIVES: Calcitonin gene-related peptide (CGRP) is released from perivascular pancreatic nerves. It effects vasomotion and cytokine liberation in inflammatory processes, including acute pancreatitis (AP). Calcitonin gene-related peptide liberation is stimulated by capsaicin, a substance of red hot chili peppers. Aim of the study was to investigate the influence of exogenous capsaicin on experimental AP. METHODS: Acute pancreatitis was induced in rats by glycodeoxycholic acid and cerulein. Animals were divided into 4 groups: (1) severe AP, (2) severe AP+capsaicin, (3) control without AP, and (4) control+capsaicin. After 24 hours, survival, histology, and CGRP were evaluated (n=6/group). In additional animals, erythrocyte flow and leukocyte activation were evaluated by intravital microscopy 6 hours after AP induction (n=6/group). RESULTS: In the control groups, all animals survived without histological alterations. Mortality in severe AP was 67%. Capsaicin reduced mortality to 16% (P<0.05). Acute pancreatitis animals developed pancreatic inflammation and necrosis, which was significantly less after capsaicin application. Intravital microscopy in severe AP showed reduced erythrocyte velocity and increased leukocyte adhesion, which was nearly normalized by capsaicin (P<0.01). Calcitonin gene-related peptide increased in both capsaicin groups, indicating endogenous CGRP liberation (P<0.01). CONCLUSION: Capsaicin releases endogenous CGRP with improved pancreatic microcirculation and reduced inflammation in experimental AP. This underlines neuropeptide activity in the pathogenesis of AP.