title: Antinociceptive effects of (1→3),(1→6)-linked β-glucan isolated from Pleurotus pulmonarius in models of acute and neuropathic pain in mice: evidence for a role for glutamatergic receptors and cytokine pathways.
abstract: The present study evaluated the antinociceptive effect of (1→3),(1→6)-linked β-glucan (GL) isolated from Pleurotus pulmonarius (Fr.) Quel. in mice and its possible mechanism of action. Intraperitoneal administration of GL inhibited glutamate-induced licking with an ID(50) of 0.34 mg/kg and inhibition of 96% ± 3%. The treatment of animals with GL (1 mg/kg i.p.) inhibited nociception induced by intrathecal injection of N-methyl-D-aspartic acid, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate and interleukin -1β in 67% ± 13%, 89% ± 11%, 74% ± 9%, and 75% ± 7%, respectively, but not the nociceptive response induced by (±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid, substance P, and tumor necrosis factor-α. Moreover, GL (30 mg/kg i.p.) also reduced mechanical allodynia caused by partial sciatic nerve ligation for 2 hours, with inhibition of 47% ± 10% observed 0.5 hours after treatment. When given chronically (twice a day) over 7 days, GL reversed the mechanical allodynia caused by partial sciatic nerve ligation (inhibition of 45% ± 13% to 60% ± 8%). Interestingly, GL did not affect the locomotor activity of mice in an open field test with doses that produce antinociceptive effects. Our findings show that GL inhibits acute and neuropathic pain in mice through mechanisms that involve the inhibition of ionotropic glutamate receptors and the interleukin -1β pathway.
  
  
  CONCLUSIONS
  This article presents the antinociceptive activity of GL in acute and neuropathic pain with participation of ionotropic glutamate receptors and pro-inflammatory cytokines (interleukin-1β). After further experiments, this compound may represent a new pharmacological agent for the treatment of clinical pain.
authors.affiliation: Department of Pharmacology, Sector of Biological Sciences, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Cristiane Hatsuko
authors.initials: CH
authors.lastname: Baggio
authors.forename: Cristina Setim
authors.initials: CS
authors.lastname: Freitas
authors.forename: Daniel Fernandes
authors.initials: DF
authors.lastname: Martins
authors.forename: Leidiane
authors.initials: L
authors.lastname: Mazzardo
authors.forename: Fhernanda Ribeiro
authors.initials: FR
authors.lastname: Smiderle
authors.forename: Guilherme Lanzi
authors.initials: GL
authors.lastname: Sassaki
authors.forename: Marcello
authors.initials: M
authors.lastname: Iacomini
authors.forename: Maria Consuelo Andrade
authors.initials: MC
authors.lastname: Marques
authors.forename: Adair Roberto Soares
authors.initials: AR
authors.lastname: Santos
mesh_terms: D000208:Acute Disease; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005936:Glucans / Q000494:pharmacology* / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000502:physiology; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D020076:Pleurotus / Q000737:chemistry*; D017470:Receptors, Glutamate / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D000700:Analgesics; D016207:Cytokines; D005936:Glucans; D053583:Interleukin-1beta; D017470:Receptors, Glutamate; C033671:epiglucan