| Abstract No.: | A-D1132 |
| Country: | Brazil |
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| Title: | PKA AND PKC ACTIVATION SEEMS TO BE THE UNDERLYING MECHANISM OF PERSISTENT HYPERNOCICEPTION INDUCED BY PGE2 IN THE HIND PAWS OF RATS. |
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| Authors/Affiliations: | 2 Mani Funez*; 1 Cristiane Villarreal; 2 Fernando Cunha; 2 Carlos Parada; 2 Sergio Ferreira;
1 Federal University of Bahia, Ribeirao Preto, Brazil; 2 FMRP-São Paulo University, Brazil
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| Content: | Objectives: The objective of this study was to investigate the contribution of two well-known kinases activated downstream in the PGE2 signaling pathway, PKA and PKC, for the hypernociception persistence induced by PGE2 in hind paws of rats. It was used two pharmacological approaches: the blocking of the hypernociceptive PGE2 stimuli sequence by pretreatment of the paws with the two-kinase inhibitors and the daily rat-hind-paw activation of these kinases.
Materials and Methods: Our method of mechanical-persistent hypernociception (MPH) is induced by 14 daily PGE2 (100ng/paw) rat hind paw hypernociception events. After this period, the hind paws in absence of conspicuous inflammatory response presents a mechanical hypernociception lasting more than thirty days. MPH was quantified in Wistar rats (male, 110-250gr) by measuring the latency until the animal presents a characteristic nociceptive behavior induced by the application of a constant pressure on the hind paws. The behavioral test was conducted twice daily before and after the injection of studied substances.
Results: PKA (AKAPI, 0.3 micrograms/100 microliters/paw) or PKCepsilon (PKCepsilon inhibitor peptide, 3 micrograms/100 microliters/paw) inhibitors alone, or their association in addition to preventing the PGE2 acute hypernociception, inhibited the MPH development. Besides, the daily activation of PKA by the administration of its catalytic subunit (3U/100microliters/paw) induced either acute or persistent hypernociception. The same profile was observed in the PKCepsilon agonist (epsilonRACK) (3U/100microliters/paw), it was noticed acute and persistent hypernociception after its administration during 14 days. It is important to mention that the administration of the PKA catalytic subunit or PKCepsilon agonist every two days did not induce MPH. Conclusion: The daily activation of the kinases PKA and PKCepsilon appears to be a key step in the PGE2 hypernociception, as well as a mechanism underlying MPH. |
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