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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2018.01119

Anti-allodynic Effect of Mangiferin in Rats with Chronic Post-ischemia Pain: A Model of Complex Regional Pain Syndrome Type I

 Barbara B. Garrido-Suarez1,  Gabino Garrido2*, Marian Castro-Labrada1, Zenia Pardo-Ruíz1, Addis Bellma Menéndez1, Evelyn Spencer1, Jozi Godoy-Figueiredo3, Sergio H. Ferreira3 and René Delgado-Hernández4
  • 1Centro de Investigación y Desarrollo de Medicamentos, Cuba
  • 2Departamento de Ciencias Farmaceuticas, Universidad Católica del Norte, Chile
  • 3Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Brazil
  • 4Instituto de Farmacia y Alimentos, University of Havana, Cuba

The present study reproduces chronic post-ischemia pain (CPIP), a model of complex regional pain syndrome type I (CRPS-I), in rats to examine the possible transient and long-term anti-allodynic effect of MG; as well as its potential beneficial interactions with some standard analgesic drugs and sympathetic-mediated vasoconstriction and vasodilator agents during the earlier stage of the pathology. A single dose of MG (50 and 100 mg/kg, p.o.) decreased mechanical allodynia 72 h post-ischemia-reperfusion (I/R). MG 100 mg/kg, i.p. (pre- vs. post-drug) increased von Frey thresholds in a yohimbine and naloxone-sensitive manner. Sub-effective doses of morphine, amitriptyline, prazosin, clonidine and a NO donor, SIN-1, in the presence of MG were found to be significantly anti-allodynic. A long-term anti-allodynic effect at 7 and 13 days post-I/R after repeated oral doses of MG (50 and 100 mg/kg) was also observed. Further, MG decreased spinal and muscle interleukin-1β concentration and restored muscle redox status. These results indicate that MG has a transient and long-term anti-allodynic effect in CPIP rats, that appears to be at least partially attributable to the opioid and α2 adrenergic receptors. Additionally, its anti-inflammatory and antioxidant mechanisms could also be implicated in this effect. The association of MG with sub-effective doses of these drugs enhances the anti-allodynic effect, however an isobolographic analysis should be performed to define a functional interaction between them. These findings suggest the possible clinical use of MG in the treatment of CRPS-I in both early sympathetically maintained pain and long-term sympathetically-independent pain.

Keywords: adrenergic receptor, Chronic post-ischemia pain, complex regional pain syndrome, Mangiferin, sympathetically maintained pain

Received: 09 Jun 2018; Accepted: 13 Sep 2018.

Edited by:

Ramón Sotomayor-Zárate, Universidad de Valparaíso, Chile

Reviewed by:

Gonzalo E. Yevenes, Universidad de Concepción, Chile
Luis Constandil, Departamento de Biologia, Facultad de Quimica y Biologia, Universidad de Santiago de Chile, Chile
Edgar Pastene, Universidad de Concepción, Chile  

Copyright: © 2018 Garrido-Suarez, Garrido, Castro-Labrada, Pardo-Ruíz, Bellma Menéndez, Spencer, Godoy-Figueiredo, Ferreira and Delgado-Hernández. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Gabino Garrido, Universidad Católica del Norte, Departamento de Ciencias Farmaceuticas, Antofagasta, Antofagasta, Chile,