Analgesic activity of fixed dose combinations of paracetamol with diclofenac sodium and paracetamol with tramadol on different pain models in healthy volunteers - A randomized double blind crossover study

AIM: To evaluate and compare the analgesic activity of fixed dose combinations (FDC) of Paracetamol with Diclofenac sodium and Paracetamol with Tramadol on different human pain models in healthy human volunteers. MATERIALS AND METHODS: A randomized double blind crossover study was carried out in 30 healthy human volunteers using three pain models; cold-water stress test, radiant heat method, and BP cuff inflation method. The subjects were randomized into two groups of 15 each, group A received FDC of Paracetamol 500 mg with Diclofenac sodium 50 mg and group B was given a FDC of Paracetamol 375 mg and Tramadol 50 mg. All the volunteers were tested on three pain models. Observations for pain tolerance were recorded at baseline and at the interval of 30, 60, 120, and 180 minutes after drug administration. Crossover was done after a washout period of 7 days. The results of both the study periods were analyzed using an independent t-test. RESULTS: Mean age of the participants was 23±1 years and the male:female ratio was 2:1. In the radiant heat method, paracetamol with tramadol combination treatment showed a significant increase in pain tolerance at 2 hours and 3 hours (P 0.028 and 0.055 respectively) compared to paracetamol with diclofenac combination. Other two pain models did not show any significant difference in the study groups. CONCLUSION: Paracetamol with tramadol combination was more effective than paracetamol with diclofenac sodium combination on the radiant heat model. In human pain models, there is an incomplete understanding of mechanisms and activated pathways are not precisely determined that needs further evaluation.