Dear Readers: Wound healing is delayed in response to chronic¹ and acute² psychological stressors. This month’s column reviews 2 recent articles that clarify the effects of psychosocial stress on wound healing. The first study shows delayed healing and depressed inflammatory cytokine production in individuals experiencing hostile marital interactions. It reminds us that our actions may affect others with broader impact than we expect. The second clarifies the biochemical mechanism(s) by which social interaction can ameliorate the negative effects on healing caused by immobilization stress in hamsters. Both studies underscore the importance of how social interactions modify the healing response and increase our awareness of how to enhance patient care.

Hostile Marital Interactions Delay Wound Healing

       Reference: Kiecolt-Glaser JK, Loving TJ, Stowell JR, et al. Hostile marital interactions, proinflammatory cytokine production, and wound healing. Arch Gen Psychiatry. 2005;62(12):1377–1384.
       Rationale: Epidemiological literature cites marital discord as a risk factor for morbidity and mortality.
       Objective: This prospective crossover study compared blister healing of married couples scoring higher or lower than median on standardized hostility tests following supportive or conflicting interactions.
       Methods: With informed consent, a volunteer sample of 42 healthy married couples aged 22–77 years were admitted to a hospital research unit on two 24-hour occasions. During the first admission, each couple participated in two 10-minute supportive sessions during which each helped the other discuss a self-improvement goal. During the second admission, the couple discussed a conflict they found disturbing. Trained observers rated all interactions, including hostility, during both sessions on the Rapid Marital Interaction Coding System (RMICS). Eight suction blisters were raised on each subject before each session, de-roofed, and sealed with a plastic template containing 70% autologous serum. Cytokine assays of IL-6, IL-1β, and TNF-α were performed on blister fluid harvested 4, 7, and 22 hours after wounding. Epidermal regeneration of these uniform-depth blisters was measured daily for 8 days and on day 12 as trans-epidermal water loss (TEWL) at each blister site and adjacent nonwounded skin. Wounds were considered healed when TEWL was restored 90% or more to normal levels.
       Results: Wound healing was slower and pro-inflammatory cytokines were higher 4 hours post interaction but rose to lower maximum levels 22 hours after the conflict situation than after the supportive sessions. Couples scoring above median hostility on RMICS during both sessions healed at 60% of the rate of low-hostility couples.
       Conclusion: These results clarify a mechanism by which everyday psychosocial stressors delay wound healing.

Social Interaction Reduces Stress-Induced Wound Healing Delay

       Reference: Detillion CE, Craft TK, Glasper ER, Prendergast BJ, DeVries AC. Social facilitation of wound healing. Psychoneuroendocrinology. 2004;29(8):1004–1011.
Rationale: Human and rodent wound healing delay in response to stress is well documented. Few studies have explored factors that benefit wound healing in stressful situations.
       Objective: The objectives of this study were to determine if positive social interaction in hamsters, which are social rodents, reduced the healing delay associated with stress immobilization and to identify the role cortisol and oxytocin play in modifying the delayed healing response.
       Methods: This was a prospective study of female Siberian hamsters raised either singly or in paired housing, exposed daily to 2 hours of restraint or no-restraint for 14 days after receiving a mid-scapular 3.5-mm dermal punch biopsy wound. One experiment compared wound contraction in 4 groups of 14 hamsters each: paired or isolated with or without the stress of restraint 2 hours daily. Another experiment measured 3-day post-wounding blood cortisol levels in the same 4 groups (n = 11–16 per group). To remove the main source of cortisol, the same effect was compared in 12–13 per group: adrenalectomized and sham-operated singly or pair-housed hamsters. Since oxytocin secretion increased in the presence of a paired sibling, further experiments explored effects of exogenous oxytocin (7 per group) and an oxytocin antagonist (5–6 per group) on the restraint-stress induced healing delay measured for 4 days after wounding.
       Results: Wound contraction was delayed in the singly housed stressed group relative to the 3 other groups. Cortisol concentrations immediately after 2 hours of restraint stress were significantly higher in the singly housed hamsters. Suppression of cortisol production by adrenalectomy restored normal healing rates. Administration of oxytocin improved wound contraction in restraint-stressed hamsters and reduced cortisol concentrations immediately after the 2-hour restraint stress. Among pair-housed hamsters, the oxytocin antagonist had a transient effect delaying repair significantly at day 2 after wounding compared to pair-housed hamsters receiving a vehicle control solution, though the study may have been underpowered to reveal consistent effects on other days.
       Conclusions: Psychological stress resulting from 2 hours of daily restraint delayed healing in Siberian hamsters unless they were housed in social pairs. This delay was associated with increased cortisol production, which occurred only in the socially isolated hamsters. Its amelioration in paired hamsters was associated with increased oxytocin. The authors conclude that social interactions in these animals buffer against psychological stress and restore normal healing through a mechanism that involves oxytocin.

Clinical Perspective

       This research suggests that not only what we do but also how we do it can make a difference to patients, particularly those experiencing the isolation often related to some institutional settings. Medical management may consider how to enable harried staff to engage in supportive behaviors to reduce the costly, time-consuming complications of delayed healing. It underscores the importance of including the patient in the wound care team and positive teaching or mentoring as the patient heals and faces new challenges, such as an ostomy or amputation. These findings also highlight the importance of positive, supportive interactions with family or friends during healing. The importance of restoring patients to their home surroundings gains new meaning in the context of these findings. Case managers may need to consider if there is a supportive family situation at home or a demanding, restraining or hostile environment. Wound care professionals can help patients by applying care based on the best available evidence enhanced by a healthy dose of positive psychosocial support.