Baclofen and midazolam alter c-fos induction by peripheral noxious or innocuous stimulation in the spinal cord of normal and monoarthritic rats

• Tipo: Outra Publicação em Revista Científica Internacional
• Data: 1999

Autores

Castro, AR (Autor) Outra; Bowery, N (Autor) Outra; Castro-Lopes J.M. (Autor) FMUP

Revista

Título: Neuropharmacology

Vol. 38

Páginas: 1775-1788

ISSN: 0028-3908

Editora: Elsevier

Indexação

ISI Web of Knowledge - 19 Citações

Scopus - 23 Citações

Outras Informações

ID Authenticus: P-001-315

DOI: 10.1016/s0028-3908(99)00138-0

Abstract (EN): In order to further clarify the role of gamma-aminobutyric acid (GABA) receptors in spinal sensory processing we have studied the effects of baclofen, a GABA(B) agonist, and midazolam, a benzodiazepine agonist, on the activation of Spinal neurones by peripheral innocuous or noxious stimulation, in normal or monoarthritic rats, as signalled by the induction of the proto-oncogene c-fos. Baclofen (10 mg/kg, i.v.) caused a significant reduction in the number of Fos-positive neurones following noxious stimulation of both normal and monoarthritic animals, which was prevented by the GABA(B) antagonist CGP 35348 (200 mg/kg, i.v.). The latter caused an increase of c-fos expression in normal animals subject to noxious stimulation, suggesting an endogenous tonic activation of GABA(B) receptors. This effect was not observed in monoarthritic animals. Baclofen also reduced the number of Fos-positive neurones in monoarthritic animals subject to innocuous stimulation. Midazolam (5 mg/kg, i.v.) had no effect in normal animals, but caused an increase in c-fos expression induced by noxious stimulation in monoarthritic animals. Flumazenil (1 mg/kg, i.v.), a benzodiazepine antagonist, prevented the effect of midazolam, and if given alone evoked a decrease in Fos-positive neurones. It can be concluded that although GABA(B) receptors modulate sensory input at the spinal level, high doses of systemic baclofen are required to inhibit nociceptive-induced c-fos expression. The paradoxical facilitation of c-fos expression by midazolam in monoarthritic animals, may be due to the reported increase in spinal GABA levels found in those animals.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 14