Oxytocin and Stress Effects on Cutaneous Wound Healing in Mice

Objective: Stress has been observed to negatively impact cutaneous wound healing in humans and rodents through the activation of the HPA axis. Oxytocin (OT), an endogenous neuropeptide, exhibits anti-stress and anti-inflammatory properties, and it has previously been shown to speed the healing of burn wounds in rodents. The purpose of this study was to evaluate the effects of different doses of OT on the wound healing rates of restraint-stressed mice in comparison to non-stressed mice. Methods: Fifty 9-week-old female SKH-1 mice were divided into two groups: food and water deprived (FWD) and restraint-stressed (RST). Each group was divided into five subgroups (n=5/group), based on type of injection received: No injection, saline, 0.1mg/kg, 0.5mg/kg, 1.0mg/kg OT. Daily subcutaneous injections were administered to the appropriate groups between 6-6:30pm throughout an 8-day interval, 3 days pre- until 5 days post-wounding. RST mice underwent restraint in 50ml well-ventilated conical tubes from 6:30pm-6:30am(dark period), while the FWD groups were not restrained. At Day 0, under anesthesia, two 3.5mm biopsy punch wounds were placed dorsally on each mouse. Wounds were assessed daily through pictures and image analysis until day 15 post-wounding. Results: 1.0mg/kg of OT was the only effective dose in accelerating wound healing rates in the FWD group, in comparison to saline-treated and non-injected controls, specifically on days 3, 4, and 6 (p<0.05). However, this same dose produced antagonistic effects on wound healing rates in the RST group, in comparison to controls, specifically on days 4 and 7 (p<0.05). Conclusion: In support of previous studies, OT appears to have positive effects on wound healing rates in non-stressed mice. However, the interactions of this neuropeptide with chronic stress appear complex and need to be further examined. Supported by NIH grant 3R21DE018161-02S1 and UIC College of Dentistry.