Background and Aims:This study compared the efficacy and safety of transdermal buprenorphine (TDB) and transdermal fentanyl (TDF) in prevention of chronic persistent post-surgical pain (CPPP) and modulation of mRNA expression of interlukin (IL-6) and mTORC1 genes in patients of head and neck carcinoma (HNC).Methods:Patients aged >18 years who were operated for HNC with numerical rating scale(NRS)pain scores≥4/10 on post-operative day-6 were enroled. A baseline assessment was done and written informed consent was obtained. The pain intensity and severity were evaluated byNRS-pain, PDQ scores (pain detect questionnaire), and neuropathic pain symptom inventory (NPSI) scores and quality of life was evaluated by utilizing Short Form-12 (SF-12). Gene expression analysis was carried out at baseline and after treatment completion. On post-operative day 6, patients of group F (n=20) received TDF (50 µg/hour) and group B (n=20) received TDB (10 µg/hour).Results:the A total of 40 patients with 20 in each group were included in this study. Following 12 weeks of treatment, gene studiesdemonstrated downregulation of the mRNA expression of IL-6 and mTORC1, which was statistically significant in both groups. A statistically significant decline in NRS-Pain, PDQ scores and NPSI scores and a statistically significant improvement in the physical and mental component scores of SF-12 was also observed in both groups (table 1).NRS Pain ScoreGroup-B Mean±SDIntra group comparison with Baseline line (P)Group-F Mean±SDIntra group comparison with Baseline line (P)Inter group comparison PBaseline7.45±1.23____7.5±7.48____1.00End of week 16.1±1.25<0.0015.15±5.63<0.0010.108End of week 25.05±1.15<0.0014.25±4.65<0.0010.252End of week 43.2±1.11<0.0013.4±3.3<0.0011.00End of week 81.8±1.11<0.0012.5±2.15<0.0010.402End of week 120.6±0.68<0.0011.29±0.93<0.0010.049SD- standard deviation, NRS -numerical rating scaleConclusion:Significant downregulation in mRNA expression of IL-6 and mTORC1 was observed after both transdermal fentanyl and transdermal buprenorphine and both were equally efficacious for prevention of CPPP and improving quality of life following HNC surgery.