Nefopam is a novel topical antifibrotic effective in the Red Duroc pig model. In a first antifibrotic study in humans, twenty-four (24) healthy volunteers received Nefopam applied to artificially induced bilateral dermal scratch wounds known to develop normotrophic and hypertrophic scar regions within the same lesion. Nefopam was applied and its safety and effect in reducing scar size assessed in a double blind, placebo-controlled, randomized protocol comparing Nefopam (1.0% or 3.0%) and placebo twice a day for 21 days according to GMP guidelines. Subjects were wounded under aseptic conditions using topical ELMA on each lateral hip using a jig that was 6 cm in length and 0 to 1.6 mm depth into the deep dermis of each lateral hip before receiving Nefopam or placebo cream in a blinded fashion. Digital photography POSAS, Mexameter®and ultrasound evaluations of the scar were performed on Day 6, 13, 20, 27, 48, 76, and 104. Biopsies were performed of each scar on Day 20 and 104. Expression of types I and III collagen, β-catenin target gene (AXIN-2), TGF-β1 and decorin, collagen orientation index, α-SMA and β-catenin staining in scar tissue was performed in addition to scar rating using VBSA and POSAS scales. Subjects were wounded under aseptic conditions using topical ELMA cream on each lateral hip using a jig that was 6 cm in length and 0 to 1.6 mm depth into the deep dermis of each lateral hip before receiving Nefopam or placebo cream in a blinded fashion. Digital photography POSAS, Mexameter®and ultrasound evaluations of the scar were performed on Day 6, 13, 20, 27, 48, 76, and 104. Biopsies were performed of each scar on Day 20 and 104. Expression of types I and III collagen, β-catenin target gene (AXIN-2), TGF-β1 and decorin, collagen orientation index (COI), α-SMA (smooth muscle actin) and β-catenin staining in scar tissue was performed in addition to scar rating using VBSA and POSAS scales. The dermal scratch model of HTS produced bilateral symmetrical wounds with normotrophic and HT regions amenable to subjective and objective assessment of the scar therapy. It demonstrated that Nefopam did inhibit β-catenin mRNA and protein staining, but 3% Nefopam slowed the rate of healing and did not reduce scar parameters when applied during the open wound phase. Future approaches to scar therapy with Nefopam include reducing its concentration and initiating the cream during the closed wound/proliferative phase of healing to exploit its antiproliferative effects. The scratch model is a novel approach to allow objective development of antifibrotic agents to control scar in burn and other patients.