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Synergistic interactions between the dual serotonergic, noradrenergic reuptake inhibitor duloxetine and the non‐steroidal anti‐inflammatory drug ibuprofen in inflammatory pain in rodents
Author(s) -
Jones Carrie K.,
Peters Steven C.,
Shan Harlan E.
Publication year - 2007
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1016/j.ejpain.2006.02.008
Subject(s) - duloxetine , ibuprofen , pharmacology , serotonergic , hyperalgesia , chemistry , analgesic , carrageenan , medicine , serotonin , anesthesia , nociception , receptor , alternative medicine , pathology
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 5min 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 (1–100mg/kg), ibuprofen alone (10–300mg/kg), or duloxetine and ibuprofen in combination in a dose‐ratio of 1:10 duloxetine:ibuprofen were orally administered 30 or 60min 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.