Efficacy of duloxetine, a potent and balanced serotonergic and noradrenergic reuptake inhibitor, in inflammatory and acute pain models in rodents.
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.
Jones
Carrie K
CK
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Peters
Steven C
SC
Shannon
Harlan E
HE
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000588:Amines / Q000494:pharmacology; D000700:Analgesics; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002351:Carrageenan; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000068736:Duloxetine Hydrochloride; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D000077206:Gabapentin; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D007052:Ibuprofen / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D000588:Amines; D000700:Analgesics; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002211:Capsaicin; D002351:Carrageenan; D003509:Cyclohexanecarboxylic Acids; D000068736:Duloxetine Hydrochloride; D018691:Excitatory Amino Acid Antagonists; D000077206:Gabapentin; D007052:Ibuprofen; D009020:Morphine; D009638:Norepinephrine; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes; D005680:gamma-Aminobutyric Acid