Fluoxetine Enhances Cutaneous Wound Healing in Chronically Stressed Wistar Rats

Objectives: To evaluate the histologic and clinical effects of fluoxetine administration on wound healing in chronically stressed and nonstressed Wistar rats.

Study Design: Full-thickness incisional wounds were created on the lower back of 72 female Wistar rats. Animals were divided into 2 stress and nonstress groups according to application of stress regimen and 3 subdivisions based on placebo, acute, or chronic administration of fluoxetine. Wound length, width, and linear healing rate based on wound area were measured for 2 weeks postwounding. Biopsies of 3 rats from each group were taken at days 1, 4, 7, and 14 to perform histomorphometric measurements by light microscopy. Analysis of covariance and analysis of variance were used to analyze wound length and other variables, respectively.

Results: Fluoxetine treatment significantly reduced mean wound length and healing period (P<.01). Although stress decreased the linear healing rate by 48%, fluoxetine treatment increased it by 68% and 31% in stressed and nonstressed rats, respectively. Stress significantly diminished infiltration of neutrophils and monocytes (P<.01), disrupted spatial organization of fibroblasts, and delayed neovascularization. Fluoxetine precluded these effects successfully.

Conclusion: Fluoxetine significantly improves healing of cutaneous wounds in stressed and, to a lesser extent, in nonstressed animals.