Przeciwbólowe efekty morfiny, nefopamu, indometacyny i imipraminy u szczurów z lezją ośrodkowego układu serotoninergicznego
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Department of Pharmacology, Medical University of Silesia, Zabrze, Poland
Przemysław Nowak   

Katedra i Zakład Farmakologii SUM w Katowicach, 41-808 Zabrze, ul. H. Jordana 38, tel./faks: +(48 32) 272 26 83
Ann. Acad. Med. Siles. 2009;63:7–24
The aim of the present study was to examine the eff ect of the central serotoninergic lesion on the antinociceptive eff ects of morphine (5.0 mg/kg sc), nefopam (20 mg/kg ip), indomethacin (5.0 mg/kg ip) and imipramine (10 mg/kg ip) in the model of exteroceptive sensation - formalin test (chemical stimulus), and interoceptive sensation - writhing test (model of visceral pain). Furthermore monoamine synthesis rate after examined analgetics in the frontal cortex, thalamus, brain stem and spinal cord was assayed.

Material and Methods:
On the 3 rd day of postnatal life male rats were administered with 5.7-DHT (70 μg/10 μl in 0.1% ascorbic acid solution ICV; 35 μg/5 μl perside); control animals received vehicle (70 μg/10 μl of 0.1% ascorbic acid solution ICV). Rats continued to be housed until 8-10 weeks, for further experimentation.

It was shown that the central serotoninergic lesion slightly modified analgesia evoked by nefopam and indomethacin in formalin test but much more profound reduction in analgesia produced by morphine and indomethacin injection was observed in visceral model of nociception. In biochemical study it was shown that analgetics employed in this study (with exception of indomethacin) altered synthesis rate of serotonin (5-HT) and dopamine (DA) in the examined parts of the rats brain. The above indicates that besides serotoninergic pathway other monoaminergic systems (noradrenergic and dopaminergic) participate in the central mechanism of action of these drugs.

It is likely that similar nociception abnormalities may occur in patients with serotoninergic system dysfunction, so that it points out on the requirement of analgetics dosage adjustment.

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