Anti-hypernociceptive effect of mangiferin in persistent and neuropathic pain models in rats

The present study examines the possible effect of the glucosylxanthone mangiferin (MG) on pain-related behaviors in a tonic acute pain model (formalin test at 5%) and in a chronic constriction injury (CCI) model to clarify the underlying transient and long-term mechanisms. Acute administration of MG...

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Published in:	Pharmacology, biochemistry and behavior Vol. 124; pp. 311 - 319
Main Authors:	Garrido-Suárez, Bárbara B., Garrido, Gabino, Castro-Labrada, Marian, Merino, Nelson, Valdés, Odalys, Rodeiro, Idania, Hernández, Ivonnes, Godoy-Figueiredo, Jozi, Ferreira, Sergio H., Delgado-Hernández, René
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-09-2014
Subjects:	Analgesics - therapeutic use Animals Behavior, Animal - drug effects Chronic constriction injury Disease Models, Animal Formalin test Hyperalgesia Male Mangiferin Neuralgia - drug therapy Neuropathic pain PC12 Cells Rats Rats, Sprague-Dawley Xanthones - pharmacology Xanthones - therapeutic use NO TNFα COX-2 RVM pNR1 WD Hyperalgesia Neuropathic pain NF-κB NMDA MG GSH HPLC DOI PGE2 Chronic constriction injury CCI DLPT IL-1β NOS PAG ROS MAO 5-HT l-NMMA Mangiferin Formalin test
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Summary:	The present study examines the possible effect of the glucosylxanthone mangiferin (MG) on pain-related behaviors in a tonic acute pain model (formalin test at 5%) and in a chronic constriction injury (CCI) model to clarify the underlying transient and long-term mechanisms. Acute administration of MG (10–100mg/kg, i.p.) reduced licking/biting exclusivity in the tonic phase of formalin test in a naloxone and yohimbine-sensitive manner. This effect was enhanced by a nonselective nitric oxide synthase (NOS) inhibitor (NG-monomethyl-l-arginine) and by a non-competitive N-methyl-d-aspartate (NMDA) antagonist (ketamine), but it was reversed by the NOS substrate (l-arginine). Pre-treatment with intrathecal yohimbine prevented the anti-hypernociceptive effect of systemic MG. Pre-treatment during 4days before surgical and 3days after CCI with MG (50mg/kg, i.p.) reduced mechanical hypernociception and decreased the signs of Wallerian degeneration (WD) of the sciatic nerve. MG improved the PC-12 cellular viability exposure to glutamate-mediated neuronal death, also involved in neuropathic pain. The findings of this study suggest that MG shows ability to decrease tonic pain in the formalin test. A transient activity of this xanthone on nociceptive pathways mediated by α2 adrenergic receptors in cooperation with the opioid system could be involved, at least in part, in this effect. Its neuroprotective effect by preventing WD in mononeuropathic rats could be implicated in the mechano-antihypernociceptive long term mechanisms. •Mangiferin (MG) shows ability to decrease tonic pain in formalin 5% test in rats•α2 adrenergic receptors and opioid system could be involved in the MG effect•MG decreases Wallerian degeneration and mechano-hypernociception in CCI rats•Interactions MG and NO- and NMDA-related compounds decrease tonic pain•MG neuroprotective effect could be involved in long term anti-hypernociception
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0091-3057 1873-5177
DOI:	10.1016/j.pbb.2014.06.019