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Pain is the most important clinical feature of acute pancreatitis (AP); however, its specific mechanism is currently unclear. In this study, we showed that AP caused an increase in nitric oxide (NO) secretion, activated the NF-κB pathway in the dorsal root ganglia (DRGs), and caused pain. We established an AP model in vivo and tested the expression of NO, the kappa opioid receptor (KOR), and pain factors. We showed that NO in AP was significantly elevated and increased the expression of pain factors. Next, by treating DRGs in vitro, it