Abdominal hyperalgesia in secretory phospholipase A2-induced rat pancreatitis: Distinct roles of NK1 receptors

We investigated the potential of secretory phospholipase A2 (sPLA2)-induced pancreatitis to promote abdominal hyperalgesia, as well as to depolarize sensory fibres in vitro using a grease-gap technique. Pancreatitis was induced by the injection of sPLA2 from Crotalus durissus terrificus (sPLA2Cdt, 300 μg kg−1) venom into the common bile duct of rats. Pancreatic inflammatory signs, serum amylase levels and abdominal hyperalgesia were evaluated in rats treated or not with SR140333, a tachykinin NK1 receptor antagonist. Injection of sPLA2Cdt caused pancreatic oedema formation and increased pancreatic neutrophil infiltration and serum amylase at 4 h, which returned to normality by 24 h, except for the neutrophil infiltration, which was still increased at this time point. Animals injected with sPLA2 exhibited a lower withdrawal threshold to electronic von Frey stimulation in the upper abdominal region at 4 h, but not 24 h, post-injection when compared with saline-injected rats. Pre-treatment of animals with SR140333 significantly reduced the sPLA2Cdt-induced abdominal hyperalgesia, without affecting the other parameters. Neither sPLA2Cdt nor sPLA2 from Naja mocambique mocambique venom depolarized capsaicin-sensitive sensory fibres from rat vagus nerve, but they decreased the propagated compound action potentials in both A and C fibres. These data show for the first time that NK1 receptors play an important role in the early abdominal hyperalgesia in a rat model of sPLA2-induced pancreatitis, suggesting that these receptors are of importance in the development of pain in the pancreatitis condition. We also provide evidence that sPLA2s do not directly depolarize sensory fibres in vitro.