Efficacy of Duloxetine, a Potent and Balanced Serotonergic and Noradrenergic Reuptake Inhibitor, in Inflammatory and Acute Pain Models in Rodents

• Published in: The Journal of pharmacology and experimental therapeutics 2005-02, Vol.312 (2), p.726-732
• Main Authors: Jones, Carrie K., Peters, Steven C., Shannon, Harlan E.
• Format: Article
• Language: English
• Subjects: Adrenergic Uptake Inhibitors - pharmacology; Amines - pharmacology; Analgesics; Analgesics, Opioid - pharmacology; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Capsaicin - pharmacology; Carrageenan; Cyclohexanecarboxylic Acids - pharmacology; Dose-Response Relationship, Drug; Duloxetine Hydrochloride; Excitatory Amino Acid Antagonists - pharmacology; gamma-Aminobutyric Acid - pharmacology; Hot Temperature; Hyperalgesia - chemically induced; Hyperalgesia - drug therapy; Ibuprofen - pharmacology; Inflammation - chemically induced; Inflammation - complications; Male; Mice; Morphine - pharmacology; Norepinephrine - metabolism; Pain - drug therapy; Pain - etiology; Pain Measurement - drug effects; Postural Balance - drug effects; Rats; Rats, Sprague-Dawley; Reaction Time - drug effects; Serotonin Uptake Inhibitors - pharmacology; Thiophenes - pharmacology
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.104.075960

Duloxetine, a selective but balanced serotonergic and noradrenergic reuptake inhibitor, was evaluated in the acute nociceptive pain models of tail flick and hot plate in mice and in the persistent and/or inflammatory pain models of acetic acid-induced writhing in mice, carrageenan-induced thermal hyperalgesia and mechanical allodynia in rats, and capsaicin-induced mechanical allodynia in rats. In acute pain models, duloxetine had no significant effect on response latency in the mouse tail-flick test but produced modest increases in response latencies in the mouse hot plate test. Morphine produced dose-related analgesic effects in both the mouse tail-flick and hot plate tests. In models of inflammatory and/or persistent pain, duloxetine, morphine, and ibuprofen produced dose-related decreases in acetic acid-induced writhing in mice. Duloxetine, ibuprofen, and gabapentin also produced dose-dependent reversals of both thermal hyperalgesia and mechanical allodynia produced by carrageenan in rats. In addition, both duloxetine and morphine produced a significant reduction of capsaicin-induced mechanical allodynia in rats. Duloxetine and gabapentin were without substantial effect on the Rotorod test in mice, whereas morphine and ibuprofen produced a significant impairment. Our data indicate that duloxetine may be efficacious in the treatment of persistent and/or inflammatory pain states at doses that have modest or no effect on acute nociception or motor performance.