CO 046: MANGIFERIN FOR THE MANAGEMENT OF PAIN: ADVANTAGES OF ITS TRANSCIENT AND LONG TERM NEUROMODULATORY EFFECTS

J Pharm Pharmacogn Res 2(Suppl. 1): S25, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 046: MANGIFERIN FOR THE MANAGEMENT OF PAIN: ADVANTAGES OF ITS TRANSCIENT AND LONG TERM NEUROMODULATORY EFFECTS

Garrido BB1, Castro M1, Rodeiro I2, Hernández I2, Pardo Z1, Menédez R1, Delgado R1.

1Drug Research and Development Center, Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600, Plaza de la Revolución, La Habana, Cuba.
2Center of Marine Bioproducts, Loma y 37, CP 10300, Nuevo Vedado, La Habana, Cuba.
Abstract

Introduction: Neuroimmune activation and nitroxidative stress are implicated in glutamatergic system dysfunction, which induces excytotoxic neural damage, desinhibition and central hyperexcitability subjacent in chronic pain. Mangiferin (MG), a naturally occurring glucoxylxanthone isolated from the standard aqueous bark extract of Mangifera indica L. shows inhibition of NF-κB signaling pathway, neuroprotective effects, antioxidant activity and it is able to limit microglial activation. Besides, reversible mono-amine oxidase (MAO) inhibitory activity is reported by xanthones, an effect that may modulate catecholamine concentration in the synaptic cleft modulating spinal nociceptive processing through the PAG/RVM/DLPT descending modulatory network. This conference focuses on unifying the cumulus of evidences around the MG effects on several animal models of pain, hypothesizing about their mechanism of actions according to a pharmacological approach.

Results: The acute administration of MG (10-100 mg/kg, i.p.) decreases licking/biting behaviors exclusivity in tonic phase of formalin 5% test. Pre-treatment with naloxone, a non selective opioid antagonist and yohimbine a selective α2 adrenergic antagonist partially reversed this effect. Intrathecal MG injection also reproduced the same behaviors. In addition, MG decreases visceral nociceptive behaviors in ovariectomized (OVX)-induced hyperalgesia in rats, which show monoamine levels decreased in brain. Preventive repeated systemic administration of MG before sciatic chronic constriction injury (CCI) in rats reduced mechanical hyperalgesia at 7 and 14 days and also decreased the signs of Wallerian degeneration of the sciatic nerve. As well as, MG improved the PC-12 cellular viability (70%) exposure to glutamate-mediated excytotoxic injury. Likewise, oral acute and chronic administration of MG in rats with chronic post-ischemia pain (CPIP), a complex regional pain syndrome type I model, decreased mechanical allodynia from 2h of MG administration and IL-1β concentration in spinal cord homogenates. A long term antihyperalgesic effects, even after discontinuation of the medication, were observed.

Conclusions: MG may modulate pathological and persistent painful status, and its anti-hyperalgesic effect could be mediated, at least in part, in the spinal cord by opioid and noradrenergic transient mechanisms. Long term effects mediated by transcriptional changes could be implicated in peripheral and central pain mechanisms, especially central sensitization.