Involvement of 5-HT1A/1B receptors in the antinociceptive effect of paracetamol in the rat formalin test

A Roca-Vinardell; E Berrocoso; M Llorca-Torralba; J A García-Partida; J Gibert-Rahola; J A Mico

doi:10.1016/j.ynpai.2018.01.004

Involvement of 5-HT_1A/1B receptors in the antinociceptive effect of paracetamol in the rat formalin test

Neurobiol Pain. 2018 Feb 1:3:15-21. doi: 10.1016/j.ynpai.2018.01.004. eCollection 2018 Jan-Jul.

Authors

A Roca-Vinardell¹, E Berrocoso^{2

3

4}, M Llorca-Torralba^{1

3

4}, J A García-Partida^{1

4}, J Gibert-Rahola^{1

3

4}, J A Mico^{1

3

4}

Affiliations

¹ Neuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, University of Cadiz, Cadiz, Spain.
² Neuropsychopharmacology and Psychobiology Research Group, Department of Psychology, University of Cadiz, Cadiz, Spain.
³ Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
⁴ Instituto de Investigación e Innovación en Ciencias Biomédicas de Cadiz, INiBICA, Hospital Universitario Puerta del Mar, Cadiz, Spain.

Abstract

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-HT_1A somatodendritic receptors, although some data also suggest the involvement of 5-HT_1B receptors. To determine whether the 5-HT_1A and 5-HT_1B 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-HT_1A and 5-HT_1B 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-HT_1A antagonist) induced an increase in the antinociceptive effect of paracetamol at 250 mg/kg doses. Conversely, 8-OH-DPAT (5-HT_1A agonist) decreased the antinociceptive effect of paracetamol at 500-1000 mg/kg doses. However, SB216641 (5-HT_1B antagonist) modified weakly the antinociceptive effect of paracetamol at 250 mg/kg doses and CP 93,129 (5-HT_1B 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-HT_1A antagonist properties in the formalin test and maybe by 5-HT_1B receptors antagonists.

Keywords: 5-HT1A receptors; 5-HT1B receptors; Antinociceptive effect; Formalin test; Paracetamol.