Synergistic interactions between the dual serotonergic, noradrenergic reuptake inhibitor duloxetine and the non-steroidal anti-inflammatory drug ibuprofen in inflammatory pain in rodents.
Eur J Pain
; 11(2): 208-15, 2007 Feb.
Article
en En
| MEDLINE
| ID: mdl-16542861
ABSTRACT
OBJECTIVES:
The present study was undertaken to characterize whether the pharmacologic interaction between duloxetine, a balanced serotonergic and noradrenergic reuptake inhibitor, and the non-steroidal anti-inflammatory drug ibuprofen was simply additive, less than additive, or greater than additive (i.e., synergistic) in preclinical models of visceral and inflammatory pain, specifically acetic acid-induced writhing in mice and carrageenan-induced thermal hyperalgesia and mechanical allodynia in rats.METHODS:
In the writhing test, male CF-1 mice were injected intraperitoneally with 0.55% acetic acid and 5 min later the number of writhes was counted over a 5-min period. In the carrageenan models, male Sprague-Dawley rats were injected with a 1.5% carrageenan solution into the ventral surface of the hind paw; hypersensitivity to thermal and mechanical stimuli was subsequently evaluated 2h post-carrageenan.RESULTS:
Vehicle or a dose of duloxetine alone (1-100 mg/kg), ibuprofen alone (10-300 mg/kg), or duloxetine and ibuprofen in combination in a dose-ratio of 110 duloxetineibuprofen were orally administered 30 or 60 min before testing. Isobolographic analysis of the effects of duloxetine in combination with ibuprofen revealed a significant synergistic (greater than additive) interaction between duloxetine and ibuprofen both for reducing acetic acid-induced writhing and carrageenan-induced thermal hyperalgesia, but were additive for reversing mechanical allodynia.CONCLUSIONS:
Our data indicate that duloxetine and ibuprofen have synergistic efficacy in a visceral and an inflammatory pain model in rodents, and suggest that duloxetine and ibuprofen in combination may provide a useful approach to the clinical treatment of persistent pain, particularly inflammation-related pain.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dolor
/
Tiofenos
/
Antiinflamatorios no Esteroideos
/
Ibuprofeno
/
Inhibidores Selectivos de la Recaptación de Serotonina
/
Inflamación
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Pain
Asunto de la revista:
NEUROLOGIA
/
PSICOFISIOLOGIA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos