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

Abstract We investigated the potential of secretory phospholipase A 2 (sPLA 2 )-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 sPLA 2 from Crotalus durissus terrificus (sPLA 2 Cdt , 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 NK 1 receptor antagonist. Injection of sPLA 2 Cdt 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 sPLA 2 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 sPLA 2 Cdt -induced abdominal hyperalgesia, without affecting the other parameters. Neither sPLA 2 Cdt nor sPLA 2 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 NK 1 receptors play an important role in the early abdominal hyperalgesia in a rat model of sPLA 2 -induced pancreatitis, suggesting that these receptors are of importance in the development of pain in the pancreatitis condition. We also provide evidence that sPLA 2 s do not directly depolarize sensory fibres in vitro .