Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2010, vol. 19, nr 1, January-February, p. 33–41

Publication type: original article

Language: English

Effect of Neonatal Serotonin Depletion on Morphine-, Nefopam-, Indomethacin-, and Imipramine-Induced Analgesia in Tests of Thermal and Mechanical Pain in Adult Rats

Wpływ zniszczenia układu serotoninergicznego u noworodków szczurzych na percepcję bólu po podaniu morfiny, nefopamu, indometacyny lub imipraminy w testach z użyciem bodźca termicznego i mechanicznego u dorosłych zwierząt

Michał Świerszcz1,, Przemysław Nowak1,, Michał Bałasz1,, Izabela Walawender1,, Jacek Kasperski2,, Dariusz Skaba3,, Elżbieta Nowak1,, Ryszard Szkilnik1,

1 Department of Pharmacology, Medical University of Silesia, Zabrze, Poland

2 Department of Prosthetic Dentistry, Medical University of Silesia, Zabrze, Poland

3 Department of Conservative Dentistry and Endodontics Division of Dental Propedeutics, Medical University of Silesia, Zabrze, Poland

Abstract

Background. Previous studies have demonstrated that chemical lesion of the noradrenergic system modified the antinociceptive effects of morphine, paracetamol, and nefopam in rats. Furthermore, it has been demonstrated that the serotoninergic as well as the noradrenergic system participate in the central effect of these drugs in different ways.
Objectives. In this study the impact of serotoninergic system lesion on the antinociceptive effects of morphine, nefopam, indomethacin, and imipramine in rats was investigated.
Material and Methods. Three days after birth, control rats were pretreated with desipramine HCl (20 mg/kg i.p., base) 30 min before intraventricular (i.c.v.) saline (0.85%)-ascorbic acid (0.1% a.a.) vehicle injection. A separate group received 5.7-dihydroxytryptamine (5,7-DHT; 70 μg in each lateral ventricle, base). When the rats attained 10 weeks of age, painful reactions were assessed by means of tail immersion and paw pressure tests. Furthermore, monoamines and their metabolite levels in some parts of the brain were determined using the HPLC/ED method.
Results. In the tail immersion test (thermal stimulus), no differences were found in the antinociceptive actions of morphine (5.0 mg/kg s.c.), nefopam (20 mg/kg i.p.), indomethacin (5 mg/kg i.p.), and imipramine (10 mg/kg i.p.) between the control and 5,7-DHT lesioned rats. In the paw pressure test (mechanical stimulus), all the examined drugs also showed a similar analgesic effect. Biochemical studies demonstrated that in the 5,7-DHT pretreated rats there was a marked decrease in serotonin (5-HT) and 5-hydroxyindoloacetic acid (5-HIAA) levels in all the examined structures (prefrontal cortex, thalamus, and spinal cord) compared with the control group (p < 0.05). Simultaneously, no changes in noradrenalin (NA) and dopamine (DA) concentrations were observed.
Conclusion. The analgesic activities of the morphine, nefopam, indomethacin, and imipramine are not perturbed by central serotoninergic system dysfunction.

Streszczenie

Wprowadzenie. Dotychczas wykazano, że przeciwbólowe działanie morfiny, paracetamolu i nefopamu zmienia się pod wpływem chemicznego uszkodzenia ośrodkowego układu noradrenergicznego u szczurów oraz że w ośrodkowych mechanizmach analgetycznego działania badanych leków uczestniczą w różnym stopniu układy serotoninergiczny i noradrenergiczny.
Cel pracy. Zbadanie wpływu chemicznej lezji ośrodkowego układu serotoninergicznego u noworodków szczurzych na przeciwbólowe działanie morfiny, nefopamu, indometacyny i imipraminy u dorosłych zwierząt.
Materiał i metody. Zwierzęta z grupy kontrolnej w 3. dniu życia otrzymały dezmetyloimipraminę (DMI; 20 mg/kg i.p.) i po 30 min dokomorowo (i.c.v.) 10 μl 0,1% roztworu kwasu askorbinowego w 0,85% chlorku sodu. Grupa z lezją układu serotoninergicznego otrzymała DMI (20 mg/kg i.p.) i po 30 min 5,7-dihydroksytryptaminę (DHT; 70 μg/10 μl i.c.v. w 0,1% roztworze kwasu askorbinowego). Gdy badane zwierzęta ukończyły 10 tygodni, wykonano testy imersji ogona oraz wycofania łapy. Dodatkowo, posługując się metodą HPLC/ED, oznaczono zawartość amin biogennych i ich metabolitów w wybranych częściach mózgu badanych zwierząt.
Wyniki. Nie stwierdzono różnicy w przeciwbólowym działaniu morfiny (5,0 mg/kg s.c.), nefopamu (20 mg/kg i.p.), indometacyny (5,0 mg/kg i.p.) i imipraminy (10 mg/kg i.p.) w teście imersji ogona (bodziec termiczny) między grupą kontrolną i 5,7-DHT. Również w teście wycofania łapy (bodziec mechaniczny) działanie przeciwbólowe stosowanych analgetyków nie różniło się między badanymi grupami zwierząt. Wykazano natomiast, że podanie 5,7-DHT w dawce 70 μg/10 μl (i.c.v.) u noworodków szczurzych wywołuje głęboki spadek zawartości serotoniny (5-HT) oraz jej metabolitu kwasu 5-hydroksyindolooctowego (5-HIAA) we wszystkich badanych strukturach mózgu, tj. korze przedczołowej, wzgórzu oraz rdzeniu kręgowym w porównaniu z grupą kontrolną (uzyskane różnice były statystycznie istotne; p < 0,05). Nie stwierdzono natomiast zmian zawartości noradrenaliny (NA), dopaminy (DA) i jej metabolitów.
Wnioski. Na podstawie przeprowadzonych badań wyciągnięto wnioski, iż zniszczenie ośrodkowego układu serotoninergicznego u szczurów nie wpływa na przeciwbólowe działanie badanych analgetyków.

Key words

serotoninergic system, lesion, antinociceptive drugs, rats

Słowa kluczowe

układ serotoninergiczny, lezja, leki przeciwbólowe, szczury

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