title: The contribution of transient receptor potential ankyrin 1 (TRPA1) to the in vivo nociceptive effects of prostaglandin E₂.
abstract: OBJECTIVE
  Although evidence suggest that TRPA1 mediates some effects of prostaglandins, it is not known whether TRPA1 contributes to the in vivo nociceptive effects of prostaglandin E2 (PGE2), a key mediator of inflammatory pain.
  
  
  METHODS
  To address this issue, the effect of the pharmacological blockade of TRPA1 or of its gene silencing on the hyperalgesia induced in the rat paw by PGE2 or its downstream signaling molecules, protein kinase A (PKA) or protein kinase C-epsilon (PKCε), was evaluated. TRPA1 expression on dorsal root ganglia cells was assessed by western blot.
  
  
  RESULTS
  The pharmacological blockade of local TRPA1 by its selective antagonist, HC 030031 decreased and reversed PGE2-induced hyperalgesia. The TRPA1 gene silencing induced by intrathecal pre-treatment with antisense oligodeoxynucleotide blocked PGE2-induced hyperalgesia and strongly reduced TRPA1 expression in dorsal root ganglia cells (L5 and L6). PGE2 injection into the hind paw did not significantly increase TRPA1 expression in dorsal root ganglia cells. Treatment with either HC 030031 or antisense oligodeoxynucleotide significantly decreased the hyperalgesia induced by PKA or PKCε. Since both kinases are the major components of PGE2-induced intracellular signal transduction, the modulation of TRPA1 function by PGE2 may be downstream PKA and PKC-epsilon.
  
  
  CONCLUSIONS
  These findings show that TRPA1 is essential to the in vivo nociceptive effects induced by one of the most important mediators of inflammatory pain, PGE2. This is one of the crucial findings necessary to support TRPA1 as a promising target for the development of future drugs to pain treatment and control.
authors.affiliation: Department of Physiology, Division of Biological Sciences, Federal University of Parana, Curitiba, Parana, Brazil.
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Dall'Acqua
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Ivan J M
authors.initials: IJ
authors.lastname: Bonet
authors.affiliation: Department of Pharmacology, Division of Biological Sciences, Federal University of Parana, Curitiba, Parana, Brazil.
authors.forename: Aleksander R
authors.initials: AR
authors.lastname: Zampronio
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Cláudia H
authors.initials: CH
authors.lastname: Tambeli
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Parada
authors.affiliation: Department of Physiology, Division of Biological Sciences, Federal University of Parana, Curitiba, Parana, Brazil. Electronic address: fischer@ufpr.br.
authors.forename: Luana
authors.initials: L
authors.lastname: Fischer
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D005346:Fibroblast Growth Factors; D005727:Ganglia, Spinal / Q000378:metabolism*; D020868:Gene Silencing; D059225:Nociception / Q000502:physiology*; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D011687:Purines / Q000494:pharmacology; D051381:Rats; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D011687:Purines; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; C108111:fibroblast growth factor 13; D005346:Fibroblast Growth Factors; D017868:Cyclic AMP-Dependent Protein Kinases; D051744:Protein Kinase C-epsilon; D015232:Dinoprostone
keywords: Inflammatory pain; Nociceptor sensitization; Prostaglandin E(2); Protein kinase A; Protein kinase C-epsilon; TRPA1