Antiallodynic Activity of Ceftriaxone and Clavulanic Acid in Acute Administration is Associated with Serum TNF-alpha Modulation and Activation of Dopaminergic and Opioidergic Systems

作者：Ochoa Aguilar A; Sotomayor Sobrino M A; Jaimez R; Rodriguez R; Plancarte Sanchez R; Ventura Martinez R^*

来源：Drug Development Research, 2017, 78(2): 105-115.

DOI：10.1002/ddr.21381

• ceftriaxone
• clavulanic acid
• neuropathic pain

The aim of this study was to determine the antiallodynic effect of acute administration of the beta-lactam antimicrobials, ceftriaxone (CFX) and clavulanic acid (CLAV), for the control of established pain on a model of neuropathic pain (NP). We also investigated the involvement of dopaminergic and opioidergic pathways as well as alterations in serum concentrations of TNF-alpha in the antiallodynic actions of these drugs. CFX, CLAV, or gabapentin (GAP), a reference drug, were administered i.p. twelve days after constriction of the sciatic nerve in rats. Mechanic and cold allodynia were evaluated for 3 h and alterations in serum concentration of TNF-alpha determined. Both CFX and CLAV had antiallodynic effects in response to mechanical and cold stimulation, similar to GAP. The antiallodynic effects of CFX and CLAV were blocked by haloperidol (HAL), a D2 receptor antagonist, and by naloxone (NLX), an opioid receptor antagonist. Additionally, serum TNF-alpha levels were attenuated following CFX and CLAV administration. These results suggest that acute administration of CFX and CLAV may represent a promising approach for treating the acute allodynia of NP, and that the mechanisms involved in these effects involve activation of dopaminergic and opioidergic pathways as well as modulation of TNF-alpha production. Drug Dev Res 78 : 105-115, 2017.

• 出版日期2017-3