Efficacy of duloxetine, a potent and balanced serotonin-norepinephrine
reuptake inhibitor in persistent pain models in rats

Iyengar S, Webster AA, Hemrick-Luecke SK, Xu JY, Simmons RM.
Eli Lilly & Co., Lilly Corporate Center,
Indianapolis, IN 46285, USA.
J Pharmacol Exp Ther. 2004 Nov;311(2):576-84


5-Hydroxytryptamine (serotonin) (5-HT) and norepinephrine (NE) are implicated in modulating descending inhibitory pain pathways in the central nervous system. Duloxetine is a selective and potent dual 5-HT and NE reuptake inhibitor (SNRI). The ability of duloxetine to antagonize 5-HT depletion in para-chloramphetamine-treated rats was comparable with that of paroxetine, a selective serotonin reuptake inhibitor (SSRI), whereas its ability to antagonize NE depletion in alpha-methyl-m-tyrosine-treated rats was similar to norepinephrine reuptake inhibitors (NRIs), thionisoxetine or desipramine. In this paradigm, duloxetine was also more potent than other SNRIs, including venlafaxine or milnacipran and amitriptyline. Low doses of the SSRI paroxetine or the NRI thionisoxetine alone did not have an effect on late phase paw-licking pain behavior in the formalin model of persistent pain; however, when combined, significantly attenuated this pain behavior. Duloxetine (3-15 mg/kg intraperitoneal) significantly attenuated late phase paw-licking behavior in a dose-dependent manner in the formalin model and was more potent than venlafaxine, milnacipran, and amitriptyline. These effects of duloxetine were evident at doses that did not cause neurologic deficits in the rotorod test. Duloxetine (5-30 mg/kg oral) was also more potent and efficacious than venlafaxine and milnacipran in reversing mechanical allodynia behavior in the L5/L6 spinal nerve ligation model of neuropathic pain. Duloxetine (3-30 mg/kg oral) was minimally efficacious in the tail-flick model of acute nociceptive pain. These data suggest that inhibition of both 5-HT and NE uptake may account for attenuation of persistent pain mechanisms. Thus, duloxetine may have utility in treatment of human persistent and neuropathic pain states.
Alpha2 antagonism
Duloxetine and the liver
Duloxetine: hope or hype?
Duloxetine and depression
Duloxetine-induced nausea
Duloxetine: a sceptical view
Duloxetine for major depression
Duloxetine for urinary incontinence
Duloxetine: efficacy and tolerability
Duloxetine (Cymbalta), serotonin and noradrenaline
Duloxetine (Cymbalta) and painful physical symptoms
Duloxetine (Cymbalta) v paroxetine (Paxil, Aropax, Seroxat)

and further reading

Future Opioids
BLTC Research
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Good Drug Guide

The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family