title: Diacerein decreases visceral pain through inhibition of glutamatergic neurotransmission and cytokine signaling in mice.
abstract: The present study evaluated the antinociceptive effect of the pro-inflammatory cytokines inhibitor diacerein in mice and its possible mechanism of action. The antinociception produced by diacerein was tested at different sites of action, moreover selective antagonists or agonists were used to identify the mechanism that may be involved in its antinociceptive action against acetic acid-induced visceral pain. Diacerein administered systemically (intraperitoneal [i.p.] or intra-gastric [i.g.] routes), supra-spinally (i.c.v.), spinally (i.t.) or peripherally (in association with the irritant agent) inhibited the visceral nociception induced by acetic acid in mice. Interestingly, diacerein treatment (25 mg/kg, i.p. or 50 mg/kg, i.g.) produced long-lasting (for up to 4 h) inhibition of acetic acid-induced nociception. Intraperitoneal treatment of mice with diacerein (25.0 mg/kg) inhibited somatic nociception induced by i.t. injection of glutamate, NMDA, kainate, and trans-ACPD but not that caused by AMPA. Diacerein (5.0-25.0 mg/kg) also produced dose related inhibition of interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) induced nociception. These results indicate that diacerein produces antinociception by inhibiting glutamatergic transmission through both ionotropic and metabotropic receptors as well as activity of pro-inflammatory cytokines.
authors: Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis-SC, Brazil.
authors: Vinícius Maria
authors: VM
authors: Gadotti
authors: Daniel Fernandes
authors: DF
authors: Martins
authors: Heyde Francine
authors: HF
authors: Pinto
authors: Gabrielle
authors: G
authors: Oliveira
authors: Manuella Pinto
authors: MP
authors: Kaster
authors: Nara Lins M
authors: NL
authors: Quintão
authors: Adair Roberto Soares
authors: AR
authors: Santos
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000378:metabolism*; D016207:Cytokines / Q000502:physiology*; D005971:Glutamates / Q000502:physiology*; D008297:Male; D051379:Mice; D010146:Pain / Q000517:prevention & control*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000880:Anthraquinones; D016207:Cytokines; D005971:Glutamates; C025292:diacerein