Synergistic interaction between matrine and paracetamol in the acetic acid writhing test in mice

The purpose of this study was to investigate the analgesic interaction between matrine and paracetamol in an acetic acid-induced writhing model in mice. Fifty percent effective dose (ED₅₀) values of the individual drugs were determined, and the different proportions of matrine and paracetamol were assayed using the isobolographic method. Our study demonstrated that both of matrine and paracetamol dose-dependently inhibited the writhing response evoked by acetic acid, and the ED₅₀ values and their 95% confidence intervals against these tonic pain were 21.10 (17.86-24.92) mg/kg and 61.30 (50.71-74.10) mg/kg for matrine and paracetamol, respectively. At the fixed ratios of 1:1, 1:3 and 3:1, the experimental ED₅₀ values of matrine and paracetamol combinations and their 95% confidence intervals were 10.52 (5.14-21.55) mg/kg, 9.13 (4.46-18.70) mg/kg and 4.98 (4.17-5.95) mg/kg, respectively, their theoretical ED₅₀ values and 95% confidence intervals were 41.20 (36.31-46.74) mg/kg, 51.25 (44.19-59.44) mg/kg and 31.15 (27.25-35.60) mg/kg, and the experimental ED₅₀ values of matrine and paracetamol combination were significantly lower than their calculated theoretical ED₅₀ values (all P < 0.01), as revealed by isobolographic analysis. Furthermore, the experimental regression line was also significantly different from the calculated additive equal-effect line over the range of the tested doses (all P < 0.01). Our results suggest that the combination of matrine with paracetamol exerts analgesic synergistic interactions in a mouse acetic acid-induced writhing model, thereby offering a possible therapeutic alternative for the clinical management of inflammatory pain.