Psychological Stress and Wound Healing in Humans

What We Know

Valentina S. Lucas, RN, MS, ANP-BC


Wounds. 2011;22(4):76-83. 

In This Article

Wound Fluid Analysis

Since numerous chemical mediators and cell types are involved in the complex process of wound healing, analysis of wound fluid provides some insight into the extracellular environment of the wound.[41,42] Wound fluid characterization provides the opportunity to obtain information reflecting the status of the wound at specific time points, and holds potential for the development of specific biomarkers of impaired healing.[43] Analysis of wound fluid provides an opportunity to potentially connect the mechanisms of psychological stress to cellular mechanisms in the local wound site.

In one prospective, longitudinal, observational study, Glaser et al[16] assessed the relationship between perceived life stress and the production of proinflammatory cytokines at the wound site. Blister wounds were created on 36 healthy female subjects and wound fluid was analyzed. Psychological tests included the 10-item Perceived Stress Scale (PSS), the Positive and Negative Affect Schedule, and the Psychiatric Epidemiological Research Inventory Life Events Scale. Health-related behaviors were also assessed. Women reporting greater stress had lower production of IL-1α [F(1,32) = 5.73, P < 0.03] and IL-8 [F(1,32) = 5.31, P <0.03] in the wound blister fluid.

In a second prospective longitudinal study, Broadbent et al15 evaluated the relationship between preoperative stress and worry and wound healing in patients undergoing routine surgical repair for an inguinal hernia. Psychological measures included the PSS, the Worry Visual Analogue Scale, and the Mental Health Index. Wound healing was determined through changes in cytokine profiles of surgical wound fluid collected from the routine manovac drain placed at the time of surgery. Higher reported preoperative psychological stress predicted impaired cellular wound repair processes in the early postoperative period. For example, higher preoperative stress significantly predicted lower levels of IL-1 in the wound fluid (β = −0.44; P = 0.03). Greater worry about the surgery predicted lower levels of matrix metalloproteinase-9 in the wound fluid (β = −0.38; P = 0.03), a more painful recovery (β = 0.51; P = 0.002), and slower recovery (β = 0.43; P = 0.01). Neither stress nor worry predicted lower levels of IL-6 levels in the wound fluid. Interestingly, researchers did not exclude smokers. Smokers had higher levels of peripheral blood MMP-9 concentrations. Prolonged MMP-9 elevation has been associated with chronic non-healing wounds.[44] Lower cytokines were also associated with higher cortisol levels.

Lastly, Kiecolt-Glaser et al[45] explored the effect of hostile marital relationships on wound healing. A group of 42 healthy married couples, aged 22 to 77 years (mean 37.04) who were married a mean of 12.55 years, were enrolled in an experimental cross-over study. Couples were engaged in a structured social support interaction during the first phase of the study, and in the second phase, were asked to discuss a marital disagreement. Psychological evaluations included the Positive and Negative Affect Schedule (PANAS) and the Marital Adjustment Test, which provided data on marital satisfaction (higher scores indicate higher satisfaction). The Rapid Marital Coding System provided data on behavior during both phases of the study. Wound fluid was evaluated for changes in cytokine levels. In addition, wound healing was measured by the rate of transepidermal water loss (TEWL) using an evaporimeter, which is a noninvasive objective method to evaluate changes in the stratum corneum barrier function of the skin.[46] They found that couples' blister wounds healed more slowly following a single 30-minute marital conflict discussion in a controlled setting in comparison to healing rates following supportive interactions (P = 0.01). Wound fluid cytokines (ie, IL-6, TNF-α, and IL-1β) were also lower after conflict in comparison to social support. Additionally, participants with high-hostility behavior healed more slowly than the low-hostility behavior group (P = 0.03).


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