Effect of drugs modulating serotonergic system on the analgesic action of paracetamol in mice

OBJECTIVE: The underlying mechanisms for the analgesic action of paracetamol (PCT) are still under considerable debate. It has been recently proposed that PCT may act by modulating the Serotonin system. This study was conducted to verify the influence of Serotonin modulating drugs (buspirone, ondansetron, and fluoxetine) on the analgesic effect of PCT. MATERIALS AND METHODS: Thirty adult albino mice were assigned to five groups: Normal saline, PCT, fluoxetine selective serotonin reuptake inhibitor (SSRI) + PCT, buspirone (5-HT(1A) Agonist) + PCT, and ondansetron (5HT(3) antagonist) + PCT. Hot-plate and formalin test were used to determine pain threshold, tests being conducted 60 min after the last treatment. Statistical analysis was done using analysis of variance followed by Dunnet's test. RESULTS: Coadministration of buspirone with PCT attenuated the antinociceptive activity of PCT (P < 0.001), whereas fluoxetine + PCT increased pain threshold in the hot-plate and formalin test (P = 0.0046). Analgesic effect of PCT was not affected by ondansetron in formalin models. It attenuated analgesic action of PCT in hot-plate test (P = 0.0137). CONCLUSION: The results suggest that 5-HT(1) receptors could also be responsible for the analgesic effect of PCT. Also, higher analgesia is produced by co-administration of SSRI (fluoxetine) + PCT.