Abstract
The possible mechanisms involved in the antinociceptive effect of venlafaxine (VFX), a selective serotonin and noradrenaline reuptake inhibitor, after a single administration and chronic treatment were investigated in a diabetic neuropathic pain (DNP) model. VFX produced a significant antihyperalgesic effect after a single and repeated administration. This effect was reversed by pretreatment with yohimbine (a relatively selective α(2)-adrenergic antagonist) and p-chloroamphetamine (a neurotoxin which destroys serotonergic neurons). Conversely, naloxone (a nonselective opioid antagonist) did not reverse the effect of VFX in a DNP model. It is concluded that both noradrenergic and serotonergic mechanisms participate in the antinociceptive effect of VFX in the DNP model. However, the noradrenergic mechanism probably plays a more important role.
Copyright © 2012 S. Karger AG, Basel.
MeSH terms
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Adrenergic Uptake Inhibitors / therapeutic use*
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Adrenergic alpha-2 Receptor Antagonists / pharmacology
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Animals
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Cyclohexanols / therapeutic use*
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Diabetes Mellitus, Experimental / complications
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Diabetes Mellitus, Experimental / drug therapy*
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Diabetes Mellitus, Experimental / physiopathology
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Hyperalgesia / drug therapy*
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Hyperalgesia / etiology
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Hyperalgesia / physiopathology
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Male
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Naloxone / pharmacology
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Narcotic Antagonists / pharmacology
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Neuralgia / drug therapy*
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Neuralgia / etiology
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Neuralgia / physiopathology
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Pain Threshold / drug effects
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Rats
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Rats, Wistar
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Selective Serotonin Reuptake Inhibitors / therapeutic use*
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Serotonin Agents / pharmacology
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Venlafaxine Hydrochloride
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Yohimbine / pharmacology
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p-Chloroamphetamine / pharmacology
Substances
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Adrenergic Uptake Inhibitors
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Adrenergic alpha-2 Receptor Antagonists
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Cyclohexanols
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Narcotic Antagonists
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Serotonin Agents
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Serotonin Uptake Inhibitors
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Yohimbine
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Naloxone
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p-Chloroamphetamine
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Venlafaxine Hydrochloride