Effective Concentration of Dipyrone in Drinking Water in a Rat Model of Post-Operative Pain

Effective reduction of post-operative pain influences surgical outcome and recovery. We determined the effective analgesic concentration of dipyrone in drinking water in a post-operative pain model. Forty male Sprague-Dawley rats underwent incision and suturing of the plantaris muscle of the hindlimb paw under anesthesia. The rats were randomized to receive one of four treatments: subcutaneous saline (Group 1/ control); intraperitoneal injection of morphine 5 mg/kg (Group 2/positive control) administered on days 0, 1, and 2 post-operatively; subcutaneous buprenorphine 0.3 mg/kg immediately pre-operatively and dipyrone 10 mg/ml and 20 mg/ml, in drinking water, immediately after the VF measurement of study day 0, and on study days 1 and 2 (Group 3 and Group 4, respectively). . Pain response was evaluated by mechanical allodynia 24 hours before surgery (baseline), and 3, 24, and 48 hours post-operatively. No statistically significant reduction in mechanical pain sensitivity was observed in saline-treated rats (control) or in animals treated with dipyrone 10 mg/ml on post-operative days 1 and 2 (p>0.05), whereas animals treated with dipyrone 20 mg/ml showed statistically significantly reduced pain sensitivity compared to the saline-treated group on both days (p<0.05). Treatment with morphine 5 mg/kg showed a statistically significant increase in the mean withdrawal force threshold compared to saline on all post-operative testing days (p<0.0001). Buprenorphine administered immediately before the surgery showed a statistically significant increase in the mean withdrawal force threshold in Group 3 vs. the saline-treated group (p<0.05). In conclusion, treatment with oral 20 mg/ml dipyrone post-operatively was effective in significantly reducing the pain sensitivity of laboratory rats.