title: Antiallodynic Activity of Ceftriaxone and Clavulanic Acid in Acute Administration is Associated with Serum TNF-α Modulation and Activation of Dopaminergic and Opioidergic Systems.
abstract: Preclinical Research The aim of this study was to determine the antiallodynic effect of acute administration of the β-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-α 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-α 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-α 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-α production. Drug Dev Res 78 : 105-115, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Departmento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, C.P. 04510, Delegación Coyoacán, Ciudad de México, México.
authors.forename: A
authors.initials: A
authors.lastname: Ochoa-Aguilar
authors.affiliation: Departmento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, C.P. 04510, Delegación Coyoacán, Ciudad de México, México.
authors.forename: M A
authors.initials: MA
authors.lastname: Sotomayor-Sobrino
authors.affiliation: Departmento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, C.P. 04510, Delegación Coyoacán, Ciudad de México, México.
authors.forename: R
authors.initials: R
authors.lastname: Jaimez
authors.affiliation: Departmento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, C.P. 04510, Delegación Coyoacán, Ciudad de México, México.
authors.forename: R
authors.initials: R
authors.lastname: Rodríguez
authors.affiliation: Clínica del Dolor, Instituto Nacional de Cancerología.
authors.forename: R
authors.initials: R
authors.lastname: Plancarte-Sánchez
authors.affiliation: Departmento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, C.P. 04510, Delegación Coyoacán, Ciudad de México, México.
authors.forename: R
authors.identifier: 0000-0002-6580-2886
authors.initials: R
authors.lastname: Ventura-Martinez
mesh_terms: D000818:Animals; D002443:Ceftriaxone / Q000008:administration & dosage* / Q000494:pharmacology; D019818:Clavulanic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D003080:Cold Temperature; D018492:Dopamine Antagonists / Q000008:administration & dosage; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000008:administration & dosage; D006930:Hyperalgesia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007274:Injections, Intraperitoneal; D008297:Male; D009270:Naloxone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000008:administration & dosage; D051381:Rats; D014110:Touch; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D018492:Dopamine Antagonists; D009292:Narcotic Antagonists; D014409:Tumor Necrosis Factor-alpha; D019818:Clavulanic Acid; D009270:Naloxone; D002443:Ceftriaxone; D006220:Haloperidol
keywords: ceftriaxone; clavulanic acid; neuropathic pain