Intraplantar PGE2 causes nociceptive behaviour and mechanical allodynia: the role of prostanoid E receptors and protein kinases

Authors

  • C A L Kassuya,

    1. Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
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  • J Ferreira,

    1. Department of Chemistry, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, Brazil
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  • R F Claudino,

    1. Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
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  • J B Calixto

    Corresponding author
    1. Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
      Departamento de Farmacologia, Universidade Federal de Santa Catarina, Campus Universitário – Trindade, Bloco D-CCB – Cx. Postal: 476 – CEP, 88049-900 – Florianópolis, Santa Catarina, Brazil. E-mails: calixto@farmaco.ufsc.br or calixto3@terra.com.br
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Departamento de Farmacologia, Universidade Federal de Santa Catarina, Campus Universitário – Trindade, Bloco D-CCB – Cx. Postal: 476 – CEP, 88049-900 – Florianópolis, Santa Catarina, Brazil. E-mails: calixto@farmaco.ufsc.br or calixto3@terra.com.br

Abstract

Background and purpose:

Receptor subtypes involved in PGE2-induced nociception are still controversial. The present study investigated the prostanoid E receptor (EP) subtypes and the protein kinase (PK) pathways involved in the nociception induced by PGE2 injection in the mouse paw.

Experimental approach:

Paw-licking and mechanical allodynia were measured in vivo and protein kinase activation ex vivo by Western blots of extracts of paw skin.

Key results:

Intraplantar (i.pl.) injection of PGE2 into the mouse paw caused nociceptive behaviour of short duration with mean ED50 of 1.43 nmol. PGE2 produced a longer-lasting mechanical allodynia, with an ED50 of 0.05 nmol. Intraplantar injection of antagonists at EP3 or EP4, but not at EP1 or EP2 receptors inhibited PGE2-induced paw-licking. Paw-licking caused by PGE2 was blocked by an inhibitor of PKA but only partially decreased by inhibition of the extracellular-regulated kinase (ERK). Selective inhibitors of PKC, c-Jun N-terminal kinase (JNK) or p38, all failed to affect PGE2-induced paw-licking. An EP3 antagonist inhibited PGE2-induced mechanical allodynia. However, inhibitors of PKA, PKC or ERK, but not p38 or JNK, also partially inhibited PGE2-induced mechanical allodynia. Western blot analyses confirmed that i.pl. injection of PGE2 activated PKA, PKCα, and mitogen activated kinases (MAPKs) in the paw. Co-treatment with EP3 or EP4 receptor antagonists reduced PGE2-induced PKA and ERK, but not PKCα activation.

Conclusions and Implications:

The present results indicate that the nociceptive behaviour and mechanical allodynia caused by i.pl. PGE2 are mediated through activation of distinct EP receptors and PK-dependent mechanisms.

British Journal of Pharmacology (2007) 150, 727–737. doi:10.1038/sj.bjp.0707149

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