Central dopaminergic system plays a role in the analgesic action of paracetamol: Preclinical evidence

Objective: Even after 100 years of discovery, the exact mechanisms for the analgesic action of paracetamol are under scanner. It was recently proposed that paracetamol may act through different mechanisms, especially altering the serotoninergic system. The main objective of this preclinical study was to verify the role of drugs modulating dopaminergic system (l-dopa, bromocriptine, olanzapine) on the analgesic effect of paracetamol. Materials and Methods: Thirty adult male albino mice were divided into five groups: distilled water (0.5 ml/25 g), paracetamol (200 mg/kg), levodopa (10 mg/kg) + paracetamol, bromocriptine (5 mg/kg) + paracetamol (200 mg/kg), and olanzapine (2 mg/kg) + paracetamol (200 mg/kg). All drugs were administered orally for 14 days. Eddy's hot plate and tail immersion tests were used to determine analgesic activity. Tests were conducted 1 h after the drug administration on the 14 th day. After that, animals were sacrificed and brains were dissected out, to measure the levels of dopamine. Statistical comparisons among the groups were performed by one-way analysis of variance followed by Tukey-Kramer test. Results: Coadministration of l-dopa and bromocriptine with paracetamol increased the antinociceptive activity of paracetamol significantly, whereas coadministration of olanzapine with paracetamol decreased the analgesic activity of paracetamol in the Eddy's hot plate and tail immersion tests considerably. There was a significant increase ( P < 0.001) in the levels of dopamine in the brains of mice, which received levodopa, bromocriptine, and paracetamol. However, it was opposite in the brains of animals which received olanzapine. Conclusion: The results suggest that analgesic action of paracetamol is influenced by dopaminergic system.