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

Abstract

IntroductionCeftriaxone (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.MethodsThe 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.ResultsBoth 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.ConclusionOur 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.

Antinociceptive effects of ceftriaxone in formalin‐induced nociception

“…Surprisingly, we found that CFX did not reach more than 30% of antinociceptive effect. These results partially agree with some reported data in inflammatory pain (Ochoa-Aguilar et al, 2018;Stepanovic-Petrovic et al, 2014). The small effect observed in our conditions could be related to the participation of different mechanism in the different models.…”

“…To our knowledge, this is the first report about the antinociceptive effect of CFX in a formalin test (1%) model, which implies an inflammatory component. Our data agree with previous studies assessing the antinociceptive effect of CFX in models of inflammatory pain, such as carrageenan, acetic acid, and surgical incision (Macaluso et al, 2013;Ochoa-Aguilar et al, 2018;Stepanovic-Petrovic et al, 2014). Moreover, it has been reported that CFX is partially effective in models of neuropathic pain in rodents (Amin et al, 2012;Eljaja et al, 2011;Gunduz et al, 2011;Hajhashemi et al, 2013;Hu et al, 2010;Ochoa-Aguilar et al, 2017;Pottabathini et al, 2016;Ramos et al, 2010;Shi et al, 2016).…”

“…Furthermore, it has also been described that CFX induced acute mechanic and thermal antiallodynic effect in an inflammatory pain model (Ochoa-Aguilar et al, 2018). Thus, the purpose of this study was to investigate the antinociceptive effect of CFX in the formalin test in rats.…”

“…Pioneer studies have shown that this antibiotic induces antinociceptive effects in chronic constriction nerve or streptozotocin injury-induced neuropathic pain (Amin, Hajhashemi, Abnous, & Hosseinzadeh, 2014;Amin, Hajhashemi, Hosseinzadeh, & Abnous, 2012;Gunduz, Oltulu, Buldum, Guven, & Ulugol, 2011;Hajhashemi, Hosseinzadeh, & Amin, 2013;Hu et al, 2010;Pottabathini, Kumar, Bhatnagar, Garg, & Ekavali, 2016;Shi, Jiang, & Li, 2016;Ochoa-Aguilar et al, 2017;Eljaja, Bjerrum, Honoré, & Abrahamsen, 2011). However, this compound has been less studied in inflammatory pain (Ochoa-Aguilar et al, 2018;Stepanovic-Petrovic, Micov, Tomic, Kovacevic, & Boškovic, 2014). In this sense, CFX produced antinociception after intraperitoneal or local administration in both somatic and visceral inflammatory pain (Stepanovic-Petrovic et al, 2014).…”

N-Acetylcysteine and Acetylsalicylic Acid Inhibit Alcohol Consumption by Different Mechanisms: Combined Protection

“…Increases in GLT-1 levels and a reduction of chronic ethanol intake following the administration of β-lactam antibiotics have also been reported by Sari and associates in rats selected as alcohol drinkers (Rao et al, 2015 ; Sari et al, 2016 ). Recent and previous studies also indicate that the β-lactam ceftriaxone displays anti-inflammatory effects (Amin et al, 2012 ; Ochoa-Aguilar et al, 2018 ).…”