title: 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, 300μgkg(-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 4h, which returned to normality by 24h, 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 4h, but not 24h, 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.
authors.affiliation: Department of Pharmacology, Institute of Biosciences (ICB-I), University of São Paulo (USP), São Paulo, 05508-900 SP, Brazil. eniltoncamargo@ufs.br
authors.forename: Enilton A
authors.initials: EA
authors.lastname: Camargo
authors.forename: Cristiane I
authors.initials: CI
authors.lastname: Zanoni
authors.forename: Marcos H
authors.initials: MH
authors.lastname: Toyama
authors.forename: Marcelo N
authors.initials: MN
authors.lastname: Muscara
authors.forename: Reginald J
authors.initials: RJ
authors.lastname: Docherty
authors.forename: Soraia K P
authors.initials: SK
authors.lastname: Costa
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D054497:Phospholipases A2, Secretory / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology; D000516:alpha-Amylases / Q000097:blood
chemical_list: D018040:Receptors, Neurokinin-1; D054497:Phospholipases A2, Secretory; D000516:alpha-Amylases