Stress Slows Wound Healing; Oxygen Helps

In a study of laboratory mice, Phillip Marucha, professor of periodontics at the UIC College of Dentistry, and his colleagues found that psychological stress, brought on by confinement, delayed the closing of wounds by more than 45 percent.

A range of cell and genetic changes accounted for the slow recovery.

"The cells that help remake tissue didn't differentiate the way they would have in normal animals. They didn't line up the way they were supposed to. And they didn't develop the tiny contractile fibers that help pull together the edges of the wound," Marucha said. "Expression of the gene that codes the protein for those fibers was impaired."

However, when the animals received hyperbaric oxygen (oxygen at a greater pressure than atmospheric oxygen), the delay in healing was almost eliminated.

Marucha said stress launches a sequence of events that constrict blood vessels and deprive the tissues of oxygen.

"Without sufficient oxygen, tissues can't heal," he said. "Oxygen activates the inflammatory cells of the immune system that help healing. Also, oxygen derivatives like bleach and peroxide are part of the arsenal of noxious products that these cells use to kill the bacteria in wounds."

The researchers hypothesized that the hyperbaric oxygen therapy reversed the delay in healing not because it relieved stress, but because it helped directly in wound healing.

To test that hypothesis, they measured levels of expression of the gene for an enzyme called inducible nitric oxide synthase, which makes nitric oxide. Nitric oxide is critically involved in wound healing, by increasing blood flow and the delivery of oxygen, and by attacking bacteria. If oxygen levels fall, the gene's activity increases.

The researchers found that when animals were stressed, expression of the gene increased, presumably to help make more nitric oxide. But when the animals received hyperbaric oxygen, gene expression returned to normal levels, suggesting that the nitric oxide levels necessary for healing had been restored by the increased tissue oxygen levels.

Other researchers involved in the study were Praveen Gajendrareddy, at UIC, and Chandan Sen, Michael Horan, Sukanya Subramanian and Arthur Strauch at Ohio State University.

The study has been published in Brain, Behavior, and Immunity and was funded by grants from the National Institutes of Health.

For more information about the UIC College of Dentistry, visit dentistry.uic.edu.