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Ceftriaxone and clavulanic acid induce antiallodynia and anti-inflammatory effects in rats using the carrageenan model

Authors Ochoa-Aguilar A, Ventura-Martinez R, Sotomayor-Sobrino MA, Jaimez R, Coffeen U, Jiménez-González A, Balcázar-Ochoa LG, Pérez-Medina-Carballo R, Rodriguez R, Plancarte-Sánchez R

Received 20 October 2017

Accepted for publication 3 April 2018

Published 21 May 2018 Volume 2018:11 Pages 977—985

DOI https://doi.org/10.2147/JPR.S154661

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Minal Joshi

Peer reviewer comments 3

Editor who approved publication: Dr Katherine Hanlon

Abraham Ochoa-Aguilar,1,2 Rosa Ventura-Martinez,1 Marco Antonio Sotomayor-Sobrino,1 Ruth Jaimez,1 Ulises Coffeen,3 Ariadna Jiménez-González,2 Luis Gerardo Balcázar-Ochoa,1 Rafael Pérez-Medina-Carballo,2 Rodolfo Rodriguez,1 Ricardo Plancarte-Sánchez4

1Pharmacology Department, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, México; 2Research Department, Mexican Faculty of Medicine, La Salle University, Mexico City, México; 3Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City, México; 4Pain Clinic, National Cancer Institute of Mexico, Mexico City, México

Introduction: Ceftriaxone (CFX) and clavulanic acid (CA) are 2 β-lactam molecules widely used as antibiotics. However, several reports of their antiallodynic properties have been published in recent years. Although this effect has been considered mostly due to a GLT1 overexpression, these molecules have also been proven to induce direct immunomodulation. In this work, we determine the acute analgesic effect of CFX and CA in an inflammatory pain model and assess if their administration may induce anti-inflammatory effects.
Methods: The carrageenan (Carr) test was used as an inflammatory pain model. Both mechanical and thermal responses were analyzed after CFX and CA administration at different times. A plethysmometer was used to determine inflammation. Also, TNF-α and IL-10 serum concentrations were determined by enzyme-linked immunosorbent assay.
Results: Both CFX and CA induced a significant thermal antiallodynic effect 3 and 24 h after administration. Furthermore, CA induced a mechanical antiallodynic effect 30, 60, and 90 min after administration. Moreover, a significant anti-inflammatory effect was found for both molecules 24 h after Carr injection. Also, both CA and CFX modulated TNF-α and IL-10 serum concentrations at different times.
Conclusion: Our results provide evidence that both CFX and CA cause an analgesic effect on a Carr inflammatory pain model and that said analgesic effect differs between each β-lactam molecule. Furthermore, this effect may be related to an anti-inflammatory effect of both molecules and a direct TNF-α and IL-10 serum concentration modulation.

Keywords: ceftriaxone, clavulanic acid, inflammatory pain, TNF-α concentration, β-lactam molecules, analgesic effect, antiallodynic properties

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