Intervention studies that improve healing outcomes by reducing psychological stress provide further evidence of the impact of psychological and behavioral factors in wound repair. Meta-analyses of clinical studies show that behavioral stress management interventions before surgery have been associated with improved post-operative outcomes, including fewer medical complications and shorter hospital stays [30
Written emotional disclosure interventions can decrease psychological distress, improve self-reported health, enhance aspects of cellular immunity, and decrease health care utilization [32
]. Men were randomized to a written emotional disclosure intervention or a non-intervention control group, and received a punch biopsy on the nondominant forearm. Healing was assessed using ultrasound biomicropsy at 3 occasions during a 21-day period. Men who participated in the emotional disclosure intervention had smaller wounds at 14 and 21 days, compared to control participants [33
Physical exercise can reduce psychological distress in addition to improving cardiovascular function [34
]. Older adults were randomized to an exercise intervention (one-hour aerobic exercise session, 3 times per week) or a non-intervention control group. One month after the beginning of the intervention, participants received a 3.5 mm punch biopsy on the back of their nondominant upper arm. Older adults who exercised healed their wounds faster than those in the control group [35
]. In accord with these human data, older mice randomized to a 30-minute daily exercise period during 8 days healed a punch biopsy wound faster than sedentary control mice [36
Social support is associated with better health outcomes [37
]. In animal studies, monogamous rodents who were housed in pairs healed a standard punch biopsy wound faster than rodents housed alone [38
]. Pair housing also buffered the impact of restraint stress on wound healing. Immobilization stress impaired cutaneous wound healing in Siberian hamsters housed alone, but not in hamsters housed in pairs [39
]. These data indicate that the presence of a familial conspecific improves wound healing outcomes in monogamous rodents.
A pharmacological agent commonly used in the treatment of mood and anxiety disorders, fluoxetine [40
]. In a study using alternating isolation and crowding stress, stressed Wistar rats who received fluoxetine healed at a similar pace as their non-stress counterparts, and faster than stressed animals who received only a vehicle injection [41
]. These results indicate that pharmacological stress reduction may also improve wound healing.
In summary, a wide array of acute and chronic stressors can disrupt the healing process. Furthermore, the impact of stress on wound repair has been observed across different methodologies and with different healing outcomes and most results have replicated in at least two independent laboratories. Collectively, results from observation, experimental, and intervention studies provide strong evidence that psychological stress can influence wound healing.