Dexmedetomidine attenuates inflammation and pancreatic injury in a rat model of experimental severe acute pancreatitis via cholinergic anti-inflammatory pathway.

Background Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis (SAP), and controlling such inflammation is vital for managing this often fatal disease. Dexmedetomidine has been reported to possess protective properties in inflammatory diseases. Therefore, this study aimed to investigate whether dexmedetomidine pre-treatment exerts an anti-inflammatory effect in rats with SAP induced by sodium taurocholate, and if so, to determine the potential mechanism. Methods SAP was induced with sodium taurocholate. Rats received an intraperitoneal injection of dexmedetomidine 30 min before sodium taurocholate administration. alpha-bungarotoxin, a selective alpha-7 nicotinic acetylcholine receptor (alpha 7nAchR) antagonist, was injected intra-peritoneally 30 min before dexmedetomidine administration. The role of the vagus nerve was evaluated by performing unilateral cervical vagotomy before the administration of dexmedetomidine. Efferent discharge of the vagal nerve was recorded by the BL-420F Data Acquisition & Analysis System. Six hours after onset, serum pro-inflammatory cytokine (tumor necrosis factor alpha [TNF-alpha] and interleukin 6 [IL-6]) levels and amylase levels were determined using an enzyme-linked immunosorbent assay and an automated biochemical analyzer, respectively. Histopathological changes in the pancreas were observed after hematoxylin and eosin staining and scored according to Schmidt criteria. Results Pre-treatment with dexmedetomidine significantly decreased serum levels of TNF-alpha, IL-6, and amylase, strongly alleviating pathological pancreatic injury in the rat model of SAP (TNF-alpha: 174.2 +/- 30.2 vs. 256.1 +/- 42.4 pg/ml; IL-6: 293.3 +/- 46.8 vs. 421.7 +/- 48.3 pg/ml; amylase: 2102.3 +/- 165.3 vs. 3186.4 +/- 245.2 U/L). However, the anti-inflammatory and pancreatic protective effects were abolished after vagotomy or pre-administration of alpha-bungarotoxin. Dexmedetomidine also significantly increased the discharge frequency and amplitude of the cervical vagus nerve in the SAP rat model (discharge frequency: 456.8 +/- 50.3 vs. 332.4 +/- 25.1 Hz; discharge amplitude: 33.4 +/- 5.3 vs. 20.5 +/- 2.9 mu V). Conclusions Dexmedetomidine administration attenuated the systemic inflammatory response and local pancreatic injury caused by SAP in rats through the cholinergic anti-inflammatory pathway involving vagus- and alpha 7nAChR-dependent mechanisms.