Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/685
Type: Artigo de periódico
Title: The peripheral pro-nociceptive state induced by repetitive inflammatory stimuli involves continuous activation of protein kinase A and protein kinase C epsilon and its Na(v)1.8 sodium channel functional regulation in the primary sensory neuron
Author: VILLARREAL, Cristiane Flora
SACHS, Daniela
FUNEZ, Mani Indiana
PARADA, Carlos Amilcar
CUNHA, Fernando de Queiroz
FERREIRA, Sergio Henrique
Abstract: In the present study, the participation of the Na(v)1.8 sodium channel was investigated in the development of the peripheral pro-nociceptive state induced by daily intraplantar injections of PGE(2) in rats and its regulation in vivo by protein kinase A (PKA) and protein kinase C epsilon (PKC epsilon) as well. In the prostaglandin E(2) (PGE(2))-induced persistent hypernociception, the Na(v)1.8 mRNA in the dorsal root ganglia (DRG) was up-regulated. The local treatment with dipyrone abolished this persistent hypernociception but did not alter the Na(v)1.8 mRNA level in the DRG. Daily intrathecal administrations of antisense Na(v)1.8 decreased the Na(v)1.8 mRNA in the DRG and reduced ongoing persistent hypernociception. once the persistent hypernociception had been abolished by dipyrone, but not by Na(v)1.8 antisense treatment, a small dose of PGE(2) restored the hypernociceptive plateau. These data show that, after a period of recurring inflammatory stimuli, an intense and prolonged nociceptive response is elicited by a minimum inflammatory stimulus and that this pro-nociceptive state depends on Na(v)1.8 mRNA up-regulation in the DRG. in addition, during the persistent hypernociceptive state, the PKA and PKC epsilon expression and activity in the DRG are up-regulated and the administration of the PKA and PKC epsilon inhibitors reduce the hypernociception as well as the Na(v)1.8 mRNA level. In the present study, we demonstrated that the functional regulation of the Na(v)1.8 mRNA by PKA and PKC epsilon in the primary sensory neuron is important for the development of the peripheral pro-nociceptive state induced by repetitive inflammatory stimuli and for the maintenance of the behavioral persistent hypernociception. (C) 2008 Elsevier Inc. All rights reserved.
Subject: Inflammatory pain
Chronic pain
Na(v)1.8 sodium channel
PKA
PKC epsilon
Primary sensory neuron
Country: Inglaterra
Editor: PERGAMON-ELSEVIER SCIENCE LTD
Citation: BIOCHEMICAL PHARMACOLOGY, v.77, n.5, p.867-877, 2009
Rights: fechado
Identifier DOI: 10.1016/j.bcp.2008.11.015
Address: http://dx.doi.org/10.1016/j.bcp.2008.11.015
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Date Issue: 2009
Appears in Collections:IB - Artigos e Materiais de Revistas Científicas

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