Comparison of milnacipran, duloxetine and pregabalin in the formalin pain test and in a model of stress-induced ultrasonic vocalizations in rats.

Abstract

Milnacipran and duloxetine, serotonin/noradrenalin reuptake inhibitors, and pregabalin, a alpha(2)-delta(1) Ca(2+) channel blocker, are efficacious against fibromyalgia, a condition characterized by diffuse chronic pain and associated with stress. We compared these compounds (i.p. route), in rat models of acute/inflammatory pain (2.5% intraplantar formalin) and stress-induced ultrasonic vocalization (USV: 22kHz calls following presentation of a conditioned stimulus previously associated with foot-shocks). In the formalin test, milnacipran dose-dependently attenuated paw elevation and licking (minimal effective dose, MED: 2.5mg/kg for licking/late phase). Duloxetine was slightly more potent (MED=0.63). Pregabalin also reduced paw licking/late phase (MED=0.63), but was inactive up to 160mg/kg for paw elevation (both phases) and paw licking (early phase). Milnacipran dose-dependently reduced USV (MED=10, near total inhibition at 20mg/kg); duloxetine was less potent (MED=20). Pregabalin (2.5-80mg/kg) was only significantly active at 40mg/kg. Milnacipran, duloxetine and pregabalin possess analgesic activity in the formalin test on paw licking/late phase (corresponding to inflammatory pain with a central sensitization component). In the stress-induced USV model, milnacipran was the most potent and efficacious compound. To summarize, reduction of formalin-induced paw licking/late phase might constitute a useful indicator of potential activity against inflammatory/centrally sensitized pain, as might be expressed in fibromyalgia.

• Authors: L Bardin, S Gregoire, M Aliaga, N Malfetes, O Vitton, P Ladure, A Newman-Tancredi, R Depoortère
• Journal: Neuroscience research (Neurosci Res) Vol. 66 Issue 2 Pg. 135-40 (Feb 2010) ISSN: 1872-8111 [Electronic] Ireland
• PMID: 19883699 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Adrenergic Uptake Inhibitors
• Analgesics
• Cyclopropanes
• Thiophenes
• Formaldehyde
• Pregabalin
• gamma-Aminobutyric Acid
• Duloxetine Hydrochloride
• Milnacipran

Topics

• Adrenergic Uptake Inhibitors (pharmacology)
• Analgesics (pharmacology)
• Analysis of Variance
• Animals
• Cyclopropanes (pharmacology)
• Dose-Response Relationship, Drug
• Duloxetine Hydrochloride
• Electroshock
• Formaldehyde (toxicity)
• Male
• Milnacipran
• Pain (chemically induced, drug therapy)
• Pain Measurement (drug effects)
• Pregabalin
• Rats
• Rats, Sprague-Dawley
• Stress, Physiological (drug effects)
• Thiophenes (pharmacology)
• Vocalization, Animal (drug effects)
• gamma-Aminobutyric Acid (analogs & derivatives, pharmacology)