Abstract:
:The unique noradrenergic and specific serotonergic antidepressant mirtazapine acts antinociceptive. It is optically active and currently marketed as racemate. In an animal model of acute pain it has been shown that the enantiomers exhibit differential effects: the R(-)-enantiomer showed anti-, the S(+)-enantiomer pronociceptive properties while the racemate acted antinociceptive at low doses and profoundly pronociceptive after high-dose application. Aim of the present study was to evaluate potential enantioselective effects of mirtazapine in neuropathic pain. In a chronic constriction injury model of neuropathic pain, Wistar rats were injected (+/-)-mirtazapine and the enantiomers intrathecally. All substances were dosed between 0.001 and 1mg/kg and compared to vehicle in a randomized and blinded approach. Thermal hyperalgesia and mechanical allodynia were assessed. In contrast to the acute pain results, only racemic mirtazapine exerted significant sustained analgesic effects up to 48 h. Antinociception was observed at all dosages with a maximum in the range of 0.01 mg/kg. Surprisingly, neither enantiomer was pro- nor antinociceptive at any dose or time. Our findings suggest that the synergism of both enantiomers is required to evoke a significant analgesic effect for the treatment of neuropathic pain. Our study gained no evidence for the use of either R(-) nor S(+)-mirtazapine alone. Due to the unique characteristics of (+/-)-mirtazapine and its proven efficacy in acute pain our results suggest that racemic mirtazapine may be a particularly useful antidepressant in the adjunctive treatment of chronic neuropathic pain states and could provide additional benefit to current therapeutic options.
journal_name
Brain Res Bulljournal_title
Brain research bulletinauthors
Muth-Selbach U,Hermanns H,Driehsen C,Lipfert P,Freynhagen Rdoi
10.1016/j.brainresbull.2008.12.015subject
Has Abstractpub_date
2009-04-06 00:00:00pages
63-8issue
1eissn
0361-9230issn
1873-2747pii
S0361-9230(08)00427-9journal_volume
79pub_type
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