A double-blind, randomized placebo-controlled clinical trial was conducted to evaluate the efficacy of combination analgesics in reducing postoperative pain in patients with irreversible pulpitis of teeth. The study included patients with moderate to severe pain with a preoperative pulpal diagnosis of irreversible pulpitis in anterior or premolar teeth.

Pulpitis can be defined as the inflammation of the tooth pulp, which consists of the blood vessels, nerve tissue, and living cells. This study included a total of 185 participants, of which 8 participants were excluded because of cross-infection, while 177 completed this study and seven were lost to follow-up. Finally, the data was collected from 170 patients (66 males and 104 females with a mean age of 33.6- 10.50 years).

There were five medications of which one was given to the enrolled patient in the form of 4 gelatinous capsules. Each dose was concealed in a white sachet containing four gelatinous capsules, and all sachets were coded and randomized.

For primary outcome measure patients were requested to identify their postoperative pain level on the Numerical Rating Scale (NRS) of 11 points (endpoints of the extremes were no pain and as bad as it could be or the worst pain) and the Visual Rating Scale (VRS) of no pain, slight pain, moderate pain or severe pain. The effectiveness of the pain medication was assessed by asking the subjects to rate their pain level every hour. A secondary outcome was to evaluate which combination with paracetamol was the most effective. The time points were defined as first 4 hours, then every 2 hours for a total of 8 hours after the initial dose, yielding a total of 6 entries. Side effects were also recorded.

From VRS-4 pain score, it was found that 54 patients (31.8%) reported moderate preoperative pain levels and 116 patients (68.2%) reported severe pain levels. Using the NRS-11, pain frequency before the treatment ranged from 4 to 10. Overall, 11 patients (6.5%) rated their pain score as 4; 19 patients (11.2%) score 5; 25 patients (14.7%) score 6; 16 patients (9.4%) score 7; 56 patients (32.9%) score 8; 38 patients (22.4%) score 9 and 5 patients (2.9%) score 10.

The primary outcome was measured on the VRS-4 scale within 8 hours after initial treatment. Within the first hour, most subjects reported no pain for all experimental groups, including the placebo group. None of the patients from paracetamol group reported severe pain within the first hour. The percentage of patients with no pain remained significantly higher than the percentage for other pain categories on the VRS-4 scale throughout the experiment, for all experimental groups. Over the first 6 hours, the pain reduction patterns were inconsistent, with some groups showing a gradual reduction in severe pain category until the 6-hour observation point and others showed increased in the severe pain category, then a decrease by the sixth hour. The Ibuprofen-Paracetamol (IP)-group was the only group that scored 0% persevere pain category by the sixth hour. After 8 hours, the Paracetamol (P) group showed a reduction in the severe pain percentage, whereas all the other groups showed an increase in the percentage of severe pain. According to the NRS-11, the IP-group showed the highest reduction in pain scores. A statistically significant difference between the pain scores before and after initial treatment for all groups was reported. There were statistically significant differences between the P and the IP groups, between the IP and Placebo (Plb) groups, and between the Diclofenac-Paracetamol (DP) and Plb groups in pain reduction. There was no significant difference between all other groups (P=0.005).

All test groups and the placebo group demonstrated pain reduction when medicated with the combinations provided. The most significant reduction in postoperative pain was found in patients treated with the IP and DP. No considerable difference between the groups treated with paracetamol and the Plb group was reported.