Involvement of 5-HT1A/1B receptors in the antinociceptive effect of paracetamol in the rat formalin test
The mechanism of analgesic action of paracetamol (acetominophen) remains still unknown. However, a relationship between serotonergic system and the effect of paracetamol has been previously demonstrated. The serotonin activity in the brainstem is primarily under the control of 5-HT1A somatodendritic...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-01-01
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| Series: | Neurobiology of Pain |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452073X17300260 |
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| author | A. Roca-Vinardell E. Berrocoso M. Llorca-Torralba J.A. García-Partida J. Gibert-Rahola J.A. Mico |
| author_facet | A. Roca-Vinardell E. Berrocoso M. Llorca-Torralba J.A. García-Partida J. Gibert-Rahola J.A. Mico |
| author_sort | A. Roca-Vinardell |
| collection | DOAJ |
| description | The mechanism of analgesic action of paracetamol (acetominophen) remains still unknown. However, a relationship between serotonergic system and the effect of paracetamol has been previously demonstrated. The serotonin activity in the brainstem is primarily under the control of 5-HT1A somatodendritic receptors, although some data also suggest the involvement of 5-HT1B receptors. To determine whether the 5-HT1A and 5-HT1B receptors are involved in the antinociceptive effect of paracetamol, we evaluated the effect of paracetamol (0.125–1 g/kg i.p.) followed by different antagonists [WAY 100,635 (0.8 mg/kg s.c.) and SB 216,641 (0.8 mg/kg s.c.)] or agonists [8-OH-DPAT (0.125 mg/kg s.c.) and CP 93,129 (0.125 mg/kg s.c.)] of 5-HT1A and 5-HT1B receptors, respectively, in the rat model of formalin-induced pain. We demonstrated that paracetamol administration showed a dose-dependent antinociceptive effect in the formalin test. WAY 100,635 (5-HT1A antagonist) induced an increase in the antinociceptive effect of paracetamol at 250 mg/kg doses. Conversely, 8-OH-DPAT (5-HT1A agonist) decreased the antinociceptive effect of paracetamol at 500–1000 mg/kg doses. However, SB216641 (5-HT1B antagonist) modified weakly the antinociceptive effect of paracetamol at 250 mg/kg doses and CP 93,129 (5-HT1B agonist) not produce a clear effect in the antinociceptive effect of paracetamol. These results suggest that the antinociceptive effect of paracetamol can be enhanced mainly by compounds having 5-HT1A antagonist properties in the formalin test and maybe by 5-HT1B receptors antagonists. Keywords: Paracetamol, Formalin test, 5-HT1A receptors, 5-HT1B receptors, Antinociceptive effect |
| first_indexed | 2024-04-12T19:10:33Z |
| format | Article |
| id | doaj.art-d3faa819a62a4695ac1a7c21dd67a37b |
| institution | Directory Open Access Journal |
| issn | 2452-073X |
| language | English |
| last_indexed | 2024-04-12T19:10:33Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Pain |
| spelling | doaj.art-d3faa819a62a4695ac1a7c21dd67a37b2022-12-22T03:19:54ZengElsevierNeurobiology of Pain2452-073X2018-01-0131521Involvement of 5-HT1A/1B receptors in the antinociceptive effect of paracetamol in the rat formalin testA. Roca-Vinardell0E. Berrocoso1M. Llorca-Torralba2J.A. García-Partida3J. Gibert-Rahola4J.A. Mico5Neuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, University of Cadiz, Cadiz, SpainNeuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cadiz, Cadiz, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación e Innovación en Ciencias Biomédicas de Cadiz, INiBICA, Hospital Universitario Puerta del Mar, Cadiz, SpainNeuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, University of Cadiz, Cadiz, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación e Innovación en Ciencias Biomédicas de Cadiz, INiBICA, Hospital Universitario Puerta del Mar, Cadiz, SpainNeuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, University of Cadiz, Cadiz, Spain; Instituto de Investigación e Innovación en Ciencias Biomédicas de Cadiz, INiBICA, Hospital Universitario Puerta del Mar, Cadiz, SpainNeuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, University of Cadiz, Cadiz, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación e Innovación en Ciencias Biomédicas de Cadiz, INiBICA, Hospital Universitario Puerta del Mar, Cadiz, SpainNeuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, University of Cadiz, Cadiz, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación e Innovación en Ciencias Biomédicas de Cadiz, INiBICA, Hospital Universitario Puerta del Mar, Cadiz, Spain; Corresponding author at: Department of Neuroscience, Pharmacology & Psychiatry, School of Medicine, University of Cádiz, Plaza Falla 9, 11003 Cádiz, Spain.The mechanism of analgesic action of paracetamol (acetominophen) remains still unknown. However, a relationship between serotonergic system and the effect of paracetamol has been previously demonstrated. The serotonin activity in the brainstem is primarily under the control of 5-HT1A somatodendritic receptors, although some data also suggest the involvement of 5-HT1B receptors. To determine whether the 5-HT1A and 5-HT1B receptors are involved in the antinociceptive effect of paracetamol, we evaluated the effect of paracetamol (0.125–1 g/kg i.p.) followed by different antagonists [WAY 100,635 (0.8 mg/kg s.c.) and SB 216,641 (0.8 mg/kg s.c.)] or agonists [8-OH-DPAT (0.125 mg/kg s.c.) and CP 93,129 (0.125 mg/kg s.c.)] of 5-HT1A and 5-HT1B receptors, respectively, in the rat model of formalin-induced pain. We demonstrated that paracetamol administration showed a dose-dependent antinociceptive effect in the formalin test. WAY 100,635 (5-HT1A antagonist) induced an increase in the antinociceptive effect of paracetamol at 250 mg/kg doses. Conversely, 8-OH-DPAT (5-HT1A agonist) decreased the antinociceptive effect of paracetamol at 500–1000 mg/kg doses. However, SB216641 (5-HT1B antagonist) modified weakly the antinociceptive effect of paracetamol at 250 mg/kg doses and CP 93,129 (5-HT1B agonist) not produce a clear effect in the antinociceptive effect of paracetamol. These results suggest that the antinociceptive effect of paracetamol can be enhanced mainly by compounds having 5-HT1A antagonist properties in the formalin test and maybe by 5-HT1B receptors antagonists. Keywords: Paracetamol, Formalin test, 5-HT1A receptors, 5-HT1B receptors, Antinociceptive effecthttp://www.sciencedirect.com/science/article/pii/S2452073X17300260 |
| spellingShingle | A. Roca-Vinardell E. Berrocoso M. Llorca-Torralba J.A. García-Partida J. Gibert-Rahola J.A. Mico Involvement of 5-HT1A/1B receptors in the antinociceptive effect of paracetamol in the rat formalin test Neurobiology of Pain |
| title | Involvement of 5-HT1A/1B receptors in the antinociceptive effect of paracetamol in the rat formalin test |
| title_full | Involvement of 5-HT1A/1B receptors in the antinociceptive effect of paracetamol in the rat formalin test |
| title_fullStr | Involvement of 5-HT1A/1B receptors in the antinociceptive effect of paracetamol in the rat formalin test |
| title_full_unstemmed | Involvement of 5-HT1A/1B receptors in the antinociceptive effect of paracetamol in the rat formalin test |
| title_short | Involvement of 5-HT1A/1B receptors in the antinociceptive effect of paracetamol in the rat formalin test |
| title_sort | involvement of 5 ht1a 1b receptors in the antinociceptive effect of paracetamol in the rat formalin test |
| url | http://www.sciencedirect.com/science/article/pii/S2452073X17300260 |
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