Objectives: To evaluate the efficacy of fixed-dose combination pharmacotherapy of Pregabalin plus Nortryptyline and compare it with Pregabalin monotherapy in patient of post-herpetic neuralgia (PHN) in modulating mRNA expression of TIMP 1 and ERK genes. Methods: A randomized, controlled study was conducted From November 2016 to April 2018. Forty patients were assessed for pain scores and the patients with NRS ≥5/10 were randomized into two groups (Group A and Group B; each group n=20). GROUP A received fixed-dose combination pharmacotherapy of Pregabalin plus Nortriptyline and Group B received Pregabalin monotherapy for 12 weeks. RT PCR was used for assessing the gene expressions of ERK and TIMP1. The primary outcome measures were changes in ERK and TIMP1expression and secondary outcome measures were change in NRS pain. Results: The baseline NRS pain score in group A was 7.45 while in group B was 6.8 (p=0.055). During the followup of 12 weeks, group A showed a significantly higher reduction in the pain score (0.8 vs 2.9, p<0.001) Compared to group B, the mRNA expression level of ERK in Group A gene was more down-regulated at 12th week (p<0.001) and for TIMP1, it was more up-regulated (0.5 fold vs 0.4 fold, p=0.046). Conclusion: The drug combination of Pregabalin plus Nortriptyline holds significant superiority over Pregabalin alone in modulating the genetic expression of TIMP1 in patients with PHN while for ERK, pregabalin alone holds importance.