It has been studied that transmembrane voltage-gated sodium channels (Nav1. 7) play a promising role in the transmission of pain. A series of Indole-and Indazole-Acylsulfonamides compounds were studied for the first time for three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis and molecular docking studies in this work. Three types of alignment methods were adopted to generate the model such as ligand based, docking based and pharmacophore-based alignments. However, the model generated using ligand-based alignment has best q2= 0.799, r2= 0.965, and other statistical parameters such as SEE= 0.133, F-value= 201.052, steric contribution= 53.40% and electrostatic contribution= 46.60%. Therefore, ligand-based alignment model was used further for model validation. Finally, contour maps generated using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models suggested the possible modification in the scaffold. The Molecular docking analysis was performed using Autodock Vina to analyze the results. In conclusion, the results based on the evidence suggested from a three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, and contour map analysis provided the insights into structural modification at specific positions. Therefore, the modification of compounds based on these studies might lead to the best active molecules having specificity to Nav1. 7 channel modulation and translate into clinical trials.