Methods: Oral mucosal and dorsal cutaneous wounds were placed on CD-1 mice to assess differences with regard to rate of healing and gene expression. Animals were subjected to restraint stress (RST) starting 3 nights prior to injury and continuing for 3 additional days post wounding. Wound closure was assessed by taking standardized pictures and measuring surface area with a commercially available software. Between treatment groups, differential gene expression for selected anti-inflammatory and pro-inflammatory cytokines, growth factors and matrix metalloproteinases (MMPs) was studied using RT-PCR. In addition, ELISAs were used to analyze protein expression of specific cytokines at different time points during the early phase of wound healing. Statistical differences between groups were determined by ANOVA followed by the Tukey test (P<0.05).
Results: Similar to what has been reported for cutaneous wounds, stress delayed healing of oral mucosal wounds. Likewise, RST suppressed IL-6 expression in both wounds. However, in contrast to cutaneous tissues, expression of IL-1 beta, MMP-8 and TIMP-1 were each induced by RST in the oral wound tissues.
Conclusions: The results of this preliminary study indicate that although RST delays healing of an oral mucosal wound like it does to cutaneous wounds, stress differentially affects the expression of those genes expressed during the early inflammatory phase of healing.