Impairment in pain perception in adult rats treated with N-(-2-chloroethyl)-N-ethyl-2- bromobenzylamine (DSP-4) as neonates
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Department of Pharmacology, Medical University of Silesia, 41-808 Zabrze, Poland
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Przemysław Nowak   

Katedra i Zakład Farmakologii SUM, 41-808 Zabrze, ul. H. Jordana 38, tel./faks +48 32 272 67 74
Ann. Acad. Med. Siles. 2009;63:67-74
This study was designed to investigate the antinociceptive eff ect of morphine, paracetamol and nefopam in rats lesioned with DSP-4 as neonates.

Intact male rats were contrasted with rats in which noradrenergic nerve terminals were largely destroyed shortly after birth with the neurotoxin DSP-4 [(N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine; 50 mg/kg S.C. x2], on the 1st and 3rd days of postnatal life. When rats attained 10 weeks of age, painful reactions were assessed by means of tail immersion test and paw pressure test. Also monoamine levels in some part of the brain were estimated using HPLC/ED method.

In the tail immersion test we showed that there are no diff erences between antinociceptive effect evoked by morphine (5.0 mg/kg sc) and paracetamol (100 mg/kg ip) between control and DSP-4 rats. Nefopam (20 mg/kg ip) elicited only slight analgesia in control rats (~ 17 %), this effect was no longer observed in the DSP-4 treated group. In the paw pressure test we demonstrated that morphine and paracetamol produced lower analgesia in DSP-4 rats in comparison to control. Nefopam evoked slight analgesia in both tested groups. In biochemical study we showed that in DSP-4 treated rats there was a marked decrease in NA level in the prefrontal cortex (to 10.4 %, p<0.01), thalamus with hypothalamus (to 54.4 %, p<0.05) and spinal cord (to 12.3 %, p<0.01) in comparison to the control group. Conversely, in the cerebellum and brain stem of DSP-4 lesioned rats there was a significant increase in the NA content versus control (respectively to 171.2 % and 123.5 % of NA in controls, p<0.05). In the striatum we did not observe any changes in NA level between examined groups. Also the levels of 5-HT and its metabolite 5-HIAA were not altered by DSP-4 treatment in all tested structures with the exception of the spinal cord (approx. 40% decrease) and the level of DOPAC (also 40% reduction). In conclusion, the obtained results showed that neonatal DSP-4 treatment alters the antinociceptive effects of examined drugs (each of them with different mechanism of action). These data lead to the proposal that perhaps there is a need to adjust the doses of analgetics applied to patients with noradrenergic system dysfunction (e.g. depression and/or anxiety disorders).

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