Ochoa-Aguilar Abraham, Ventura-Martinez Rosa, Sotomayor-Sobrino Marco Antonio, Jaimez Ruth, Coffeen Ulises, Jiménez-González Ariadna, Balcázar-Ochoa Luis Gerardo, Pérez-Medina-Carballo Rafael, Rodriguez Rodolfo, Plancarte-Sánchez Ricardo
Pharmacology Department, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, México.
Research Department, Mexican Faculty of Medicine, La Salle University, Mexico City, México.
J Pain Res. 2018 May 21;11:977-985. doi: 10.2147/JPR.S154661. eCollection 2018.
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.
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.
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.
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.
头孢曲松(CFX)和克拉维酸(CA)是两种广泛用作抗生素的β-内酰胺类分子。然而,近年来已有多篇关于它们抗痛觉过敏特性的报道。尽管这种作用大多被认为是由于谷氨酸转运体1(GLT1)过表达所致,但这些分子也已被证明可诱导直接的免疫调节作用。在本研究中,我们确定了CFX和CA在炎症性疼痛模型中的急性镇痛作用,并评估其给药是否可能诱导抗炎作用。
角叉菜胶(Carr)试验被用作炎症性疼痛模型。在不同时间给予CFX和CA后,分析机械性和热反应。使用体积描记器测定炎症。此外,通过酶联免疫吸附测定法测定肿瘤坏死因子-α(TNF-α)和白细胞介素-10(IL-10)的血清浓度。
CFX和CA在给药后3小时和24小时均诱导出显著的热抗痛觉过敏作用。此外,CA在给药后30、60和90分钟诱导出机械性抗痛觉过敏作用。而且,在注射Carr后24小时发现这两种分子均具有显著的抗炎作用。此外,CA和CFX在不同时间调节TNF-α和IL-10的血清浓度。
我们的结果提供了证据,表明CFX和CA对Carr炎症性疼痛模型均有镇痛作用,且每种β-内酰胺类分子的镇痛作用有所不同。此外,这种作用可能与这两种分子的抗炎作用以及直接调节TNF-α和IL-10血清浓度有关。