Efficacy of duloxetine, a potent and balanced serotonergic and noradrenergic reuptake inhibitor, in inflammatory and acute pain models in rodents.

Abstract

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.

• Authors: Carrie K Jones, Steven C Peters, Harlan E Shannon
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 312 Issue 2 Pg. 726-32 (Feb 2005) ISSN: 0022-3565 [Print] United States
• PMID: 15494550 (Publication Type: Journal Article)

Chemical References

• Adrenergic Uptake Inhibitors
• Amines
• Analgesics
• Analgesics, Opioid
• Anti-Inflammatory Agents, Non-Steroidal
• Cyclohexanecarboxylic Acids
• Excitatory Amino Acid Antagonists
• Serotonin Uptake Inhibitors
• Thiophenes
• gamma-Aminobutyric Acid
• Gabapentin
• Morphine
• Carrageenan
• Duloxetine Hydrochloride
• Capsaicin
• Ibuprofen
• Norepinephrine

Topics

• 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)
• Gabapentin
• Hot Temperature
• Hyperalgesia (chemically induced, drug therapy)
• Ibuprofen (pharmacology)
• Inflammation (chemically induced, complications)
• Male
• Mice
• Morphine (pharmacology)
• Norepinephrine (metabolism)
• Pain (drug therapy, etiology)
• Pain Measurement (drug effects)
• Postural Balance (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reaction Time (drug effects)
• Selective Serotonin Reuptake Inhibitors (pharmacology)
• Thiophenes (pharmacology)
• gamma-Aminobutyric Acid (pharmacology)