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.
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.
Baggio
Cristiane Hatsuko
CH
Department of Pharmacology, Sector of Biological Sciences, Federal University of Paraná, Curitiba, PR, Brazil.
Freitas
Cristina Setim
CS
Martins
Daniel Fernandes
DF
Mazzardo
Leidiane
L
Smiderle
Fhernanda Ribeiro
FR
Sassaki
Guilherme Lanzi
GL
Iacomini
Marcello
M
Marques
Maria Consuelo Andrade
MC
Santos
Adair Roberto Soares
AR
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
D000700:Analgesics; D016207:Cytokines; D005936:Glucans; D053583:Interleukin-1beta; D017470:Receptors, Glutamate; C033671:epiglucan