Acute pancreatitis (AP) is an acute abdominal disease characterised by inflammation of the pancreas. Acute severe upper abdominal pain is the leading symptom and primary reason for emergence hospital admission of AP patients. Nowadays, more and more research has focused on the cross-talk between the exocrine pancreas and pancreatic projecting neurons (neurogenic inflammation) for pain in AP. Elucidating the molecular mechanisms of neurogenic inflammation for pain in AP will provide insights into targeted analgesics development in this setting.
ObjectiveTo investigate the effects of generic interleukin (IL)-17A gene knockout (IL-17AKO) on pancreatic and intestinal barrier on acute pancreatitis (AP) in mice. MethodsIL-17AKO mice and their wild type (WT) littermates were employed to induce AP using cerulein (CER) and sodium taurocholate (NaTC). In the CER-AP experiment, mice were randomly divided into three groups: WT control group, WT model group, and IL-17AKO model group (n=5). Mice in the model group were intraperitoneally injected with CER [50 μg/(kg·h), 7 injections], and control group received intraperitoneal injection the same amount of 0.9% NaCl. The mice were sacrificed at 12 hours after the first injection of CER. The levels of serum amylase, lipase and IL-6 were detected, and the pancreas was stained with hematoxylin-eosin (HE). In the NaTC-AP experiment, WT mice were randomly divided into sham group (n=3) and operation model group (n=6). Similarly, IL-17AKO mice were also randomly allocated to sham group (n=3) and operation model group (n=6). The mice in the sham group underwent a surgical procedure on the abdomen only, whereas in the model group, 50 μL 3.5% NaTC dissolved in saline solution was pumped into the pancreatobiliary duct. Serum amylase, lipase, and IL-6 levels were detected. Pancreas was stained with HE, and intestine was stained with Alcian blue-periodic acid-Schiff, Dolichos Biflorus Agglutinin and bacteria fluorescence in situ hybridization. ResultsIn the CER-AP experiment, there were no significant differences in serum amylase, lipase, IL-6, and pathological changes including edema, inflammation, necrosis, and total pathological score of the pancreas between IL-17AKO and WT mice (P>0.05). In the NaTC-AP experiment, compared to the WT model group, IL-17AKO did not significantly impact serum amylase, lipase, and pancreatic pathological changes (P>0.05). However, it did lead to an increased level of IL-6 (P<0.05), and showed no significant protective effect on intestinal injury in NaTC-AP. Compared to WT mice of sham group, IL-17AKO mice of sham group exhibited decreased expressions of glycosylated mucin in ileum and colon, disordered mucus layer structure, and increased bacterial invasion. ConclusionsIL-17AKO has no significant protective effect on pancreatic and intestinal barrier damage in AP mice. Furthermore, it was discovered that prior to modeling, IL-17AKO mice exhibited higher bacterial invasion, intestinal barrier disruption, and a systemic inflammatory response. These findings imply that IL-17A plays a crucial role in immune responses and the maintenance of physiological intestinal barrier function in mice.
Pain is one of the main presenting symptoms in patients with acute pancreatitis (AP) and is also an important clinical factor affecting fluid resuscitation, enteral nutrition, early mobilization, organ support, and post-discharge recovery. The 2026 European interdisciplinary guidelines on pain management in AP were developed using a high-quality guideline development framework and generated 41 consensus-based recommendations across nine topics: general principles of acute pain management, pain pathophysiology, pain assessment, pharmacological treatment, epidural analgesia, complementary therapies, the impact of pain control on clinical outcomes, management of special populations, and discharge and follow-up. The key recommendations include that opioid use should not be delayed in patients with severe pain because of theoretical safety concerns; non-steroidal anti-inflammatory drugs generally do not increase adverse events or worsen AP severity; patient-controlled intravenous analgesia should not be used as a routine strategy; epidural analgesia may have potential benefits in severe AP; acupuncture and Chaiqin Chengqi decoction may be considered as limited adjunctive treatment options; and routine imaging follow-up is not supported for patients with pain after discharge, with selective investigations recommended based on clinical indications. This guideline interpretation discusses the key recommendations, evidence base, and implementation considerations in the context of clinical practice in China, aiming to provide a reference for standardizing AP pain management and optimizing patient outcomes.