Antinociceptive effects of the antidepressants amitriptyline, duloxetine, mirtazapine and citalopram in animal models of acute, persistent and neuropathic pain
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Abstract
The effects of acute, systemic administration of amitriptyline, duloxetine and mirtazapine
(antidepressant drugs that variously affect extracellular noradrenaline and serotonin
levels) and the selective serotonin reuptake inhibitor (SSRI) citalopram were compared
in rat models of experimental pain. None of the drugs (all 3-30 mg/kg, i.p.) affected
acute nociceptive responses as measured in the tail flick test. In the hot plate test,
duloxetine and mirtazapine significantly increased (P<0.05) the nociceptive response
latency, whereas amitriptyline and citalopram were ineffective. In the formalin test,
duloxetine and citalopram significantly attenuated, whereas amitriptyline and mirtazapine
increased, second phase flinching behaviour (all P<0.05). However, amitriptyline and
mirtazapine reduced second phase licking behaviour. In the chronic constriction injury
model of neuropathic pain, thermal hyperalgesia of the injured hindpaw was significantly
attenuated by all four drugs (P<0.05); only amitriptyline and duloxetine fully reversed
thermal hypersensitivity. None of the drugs tested attenuated mechanical allodynia.
In contrast amitriptyline, duloxetine and mirtazapine significantly reduced mechanical
hyperalgesia (P<0.05); citalopram was ineffective. No drug-related effects on motor
performance in the rotarod test were observed. These results (a) highlight the difficulty
in correlating antinociceptive effects of drugs from different antidepressant classes
across a range of animal pain models and (b) suggest that antidepressants that variously
affect both noradrenaline and serotonin levels have more potent and efficacious antinociceptive
effects than SSRIs (as exemplified by citalopram), against a range of pain-like behaviours
in an animal model of neuropathic pain.