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The spinal inhibition of N-type voltage-gated calcium channels selectively prevents scratching behavior in mice.
Maciel, I S; Azevedo, V M; Pereira, T C; Bogo, M R; Souza, A H; Gomez, M V; Campos, M M.
Afiliação
  • Maciel IS; Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Institute of Toxicology and Pharmacology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
  • Azevedo VM; Institute of Toxicology and Pharmacology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Faculty of Pharmacy, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
  • Pereira TC; Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Laboratory of Genomics and Molecular Biology, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
  • Bogo MR; Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Laboratory of Genomics and Molecular Biology, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Postgraduate Progr
  • Souza AH; Laboratory of Neuroscience, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
  • Gomez MV; Laboratory of Neuroscience, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
  • Campos MM; Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Institute of Toxicology and Pharmacology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Faculty of Dentistry, Pontifical Catholic Univ
Neuroscience ; 277: 794-805, 2014 Sep 26.
Article em En | MEDLINE | ID: mdl-25108164
The present study investigated the effects of pharmacological spinal inhibition of voltage-gated calcium channels (VGCC) in mouse pruritus. The epidural administration of P/Q-type MVIIC or PhTx3.3, L-type verapamil, T-type NNC 55-0396 or R-type SNX-482 VGCC blockers failed to alter the scratching behavior caused by the proteinase-activated receptor 2 (PAR-2) activator trypsin, injected into the mouse nape skin. Otherwise, trypsin-elicited pruritus was markedly reduced by the spinal administration of preferential N-type VGCC inhibitors MVIIA and Phα1ß. Time-course experiments revealed that Conus magus-derived toxin MVIIA displayed significant effects when dosed from 1h to 4h before trypsin, while the anti-pruritic effects of Phα1ß from Phoneutria nigriventer remained significant for up to 12h. In addition to reducing trypsin-evoked itching, MVIIA or Phα1ß also prevented the itching elicited by intradermal (i.d.) injection of SLIGRL-NH2, compound 48/80 or chloroquine, although they did not affect H2O2-induced scratching behavior. Furthermore, the co-administration of MVIIA or Phα1ß markedly inhibited the pruritus caused by the spinal injection of gastrin-releasing peptide (GRP), but not morphine. Notably, the epidural administration of MVIIA or Phα1ß greatly prevented the chronic pruritus allied to dry skin model. However, either tested toxin failed to alter the edema formation or neutrophil influx caused by trypsin, whereas they significantly reduced the c-Fos activation in laminas I, II and III of the spinal cord. Our data bring novel evidence on itching transmission mechanisms, pointing out the therapeutic relevance of N-type VGCC inhibitors to control refractory pruritus.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Prurido / Medula Espinal / Bloqueadores dos Canais de Cálcio / Canais de Cálcio Tipo N / Antipruriginosos Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Prurido / Medula Espinal / Bloqueadores dos Canais de Cálcio / Canais de Cálcio Tipo N / Antipruriginosos Idioma: En Ano de publicação: 2014 Tipo de documento: Article