Stress and Wound Healing

Type of stress

Study design




Evaluated relationship between acute post-operative pain intensity and time to healing of a standard 2 mm punch biopsy wound in women

Women who reported higher levels of acute post-operative pain experienced slower wound healing while those who reported lower levels of persistent post-operative pain experienced faster wound healing; depressive symptoms on day of surgery did not affect wound healing but directly correlated with presence of persistent pain

Mcguire et al. [49]


Evaluated effect of thrombocytopenia on immune function and dermal wound healing in thrombocytopenic rats versus control rats

Thrombocytopenia altered the inflammatory response and immune function measured by increased number of macrophages and T cells in thrombocytopenic rats compared to control rats; there was no difference in wound closure, angiogenesis, or collagen synthesis between groups

Szpaderska et al. [43]


Evaluated effect of acute pain on time to recovery of barrier function after forearm skin injury in healthy men and women

Greater acute pain was associated with faster recovery of barrier function in men and women with dermal abrasions compared to their own control abrasion and subjects who reported lower pain levels

Graham et al. [48]

Acute and Chronic

Evaluated effect of acute and chronic stress on cell-mediated immune response in rats

Acute stress enhanced cell-mediated immunity by causing T-cells to be redistributed to the skin whereas chronic stress suppressed cell-mediated immunity by causing T-cells to be diverted away from the skin in a delayed type hypersensitivity reaction

Dhabhar et al. [44]


Evaluated effect of caregiver stress on sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal axes in 10 caregivers and 10 age- and weight-matched control subjects

Chronic caregiver stress was associated with a significant decrease (50 %) in GH mRNA expression in peripheral blood mononuclear cells compated to age- and weight-matched controls; GH mRNA levels were negatively correlated with plasma ACTH and norepinephrine levels

Malarkey et al. [41]


Evaluated healing of a 3.5 mm punch biopsy wound in 13 women caring for a relative with Alzheimer’s disease and 13 controls matched for age and family income

Chronic psychological stress caused significantly delayed wound healing of a 3.5 mm punch biopsy wound (48.7 vs 39.3 days) and decreased IL-1 mRNA expression in peripheral leukocytes in response to lipopolysaccharide stimulation compared to control subjects

Kiecolt-Glaser et al. [40]


Evaluated effect of glucocorticoid receptor antagonist, RU486, on cutaneous wound healing in chronically stressed mice

Glucocorticoid receptor antagonist improved cutaneous wound healing as measured by earlier wound contraction and improved angiogenesis in treated stressed mice compared to untreated stressed mice

Almeida et al. [38]


Evaluated effect of chronic restraint stress on cutaneous wound healing of a 3.5 mm punch biopsy in mice

Restraint stress was associated with higher circulating corticosteroid levels and with a 27 % reduction in cutaneous wound healing in stressed mice compared to control mice

Padgett et al. [50]

Table 19.2
Impact of stress management on wound healing

Type of stress






Patient education: Behavioral stress management interventions before surgical procedures

Meta-analyses of clinical studies providing patient information about the surgical procedure and behavioral instructions

Demonstrated better post-operative outcomes, such as fewer medical complications, faster ambulation, decreased hospital length of stay, and reduced use of analgesia

Johnston et al. [55]


Written emotional disclosure

Evaluated healing of a punch biopsy wound on the nondominant forearm in men randomized to a written emotional disclosure intervention or a non-intervention control group

Healing was assessed using ultrasound biomicroscopy at 3 occasions during a 21-day period. Those who participated in the emotional disclosure intervention had smaller wounds at 14 and 21 days compared to control participants

Weinman et al. [66]


Physical exercise

Evaluated healing of 3.5 mm punch biopsy wound in older adults randomized to an exercise intervention with aerobic workouts 3 days per week or a non-intervention control group.

Evaluated healing of punch biopsy wound in older mice, randomized to a 30-min daily exercise program for 8 days, or a sedentary control group

Those engaging in regular exercise experienced wound healing in a mean of 29 days compared to 39 days for the inactive control group.

Older mice that were randomized to a daily exercise program experienced faster wound healing of a punch biopsy than sedentary control mice

Emery et al. [67]

Keylock et al. [69]


Determine quality of life using Chronic Venous Insufficiency Questionnaire (CVIQ) scale

Evaluated the relationship between the amount of time spent on wound care and the patient’s feelings of anger and resentment in 73 patients with venous ulcers

Found that there is a strong correlation between the amount of time spent on ulcer care and feelings of anger and resentment. 68 % of patients reported that the ulcer had a negative emotional impact on their lives including feelings of fear, social isolation, anger, depression, and negative self-image

Wilson [63]

Phillips et al. [60]


Compression therapy

Examined the effects of standard wound care treatment on health-related quality of life in patients with leg ulcers.

Patients whose ulcers were healing experienced significant improvements in lower extremity pain, increased energy, decreased anxiety, and better sleep.

Franks et al. [64]


Wound treatment:

 Debridement, local and systemic pharmacological treatment, exercise, leg elevation, antibiotics in the presence of infection, and special wound dressings

Evaluated the prevalence of anxiety and depression in 190 patients with chronic venous ulceration

Demonstrated that pain and odor were the two findings commonly associated with depression and anxiety in chronic venous ulcer patients. Living alone, decreased mobility, and presence of exudate was not associated with depression and anxiety.

Local wound treatment is associated with pain relief and odor minimization

Jones et al. [58]

Lebrun et al. [59]


Social support or social networking

Evaluated healing of punch biopsy wound in monogamous rodents who were housed in pairs compared with rodents housed alone.

Evaluated cytokine levels in the wounds and circulating proinflammatory cytokines IL-6 and TNF-α in hostile couples

Rodents in pairs healed a standard punch biopsy wound faster than rodents housed alone. Paired housing also reduced the impact of restraint stress on wound healing.

Reduced cytokine levels in the wound as well as increased circulating IL-6 and tumor necrosis factor (TNF)-α are found in unsympathetic or hostile couples. This is associated with a reduction in wound healing

Glasper et al. [71]

Detillion et al. [72]

Kiecolt-Glaser et al. [40]


Pharmacological stress reduction

Evaluated the effect of fluoxetine in Wistar rats undergoing alternating isolation and crowding stress.

Evaluated the effect of propranolol on the wound healing process in burns.

Evaluated the effect of isoproterenol on the wound healing process.

Evaluated the effect of timolol on expression levels of the beta2-adrenergic receptor (B2AR), and the catecholamine synthetic enzymes tyrosine hydroxylase and phenylethanolamine-N-methyltransferase.

Stressed Wistar rats who received fluoxetine healed at a similar rate as their non-stressed counterparts, and faster than stressed control animals.

Propranolol administration appears to counteract the stress-induced delay in wound contraction and re-epithelialization, reverse the reduction in epidermal proliferation, attenuate the delay in the inflammatory response and the impairment in granulation tissue formation, as well as reduce metalloproteinase activity.

Isoproterenol decreased keratinocyte migratory speed, reduced in vitro scratch-wound closure, and delayed ex vivo human wound re-epithelialization.

Cultured keratinocytes showed that wounding downregulated B2AR, tyrosine hydroxylase, and phenylethanolamine-N-methyltransferase expression, but pre-exposure to timolol delayed this effect

Farahani et al. [75]

Denda et al. [77]

Pullar et al. [78]

Sivamani et al. [79]

Pullar et al. [80]

Pullar et al. [81]

Pullar et al. [78]

Sivamani et al. [76]

Romana-Souza et al. [83]

Sivamani et al. [79]

Acute and chronic

Relaxation/mindfulness based stress reduction: Meditation, Yoga

Evaluated effect of relaxation and mindfulness based stress reduction on surgical wounds

A brief relaxation intervention can reduce stress and improve collagen deposition in surgical wounds.

Yoga has been attributed to shorter postoperative hospital stays, earlier drain removal, and decreased TNF-alpha levels for wound healing in early operable breast cancer patients undergoing surgery.

Patients receiving relaxation guided imagery exhibited reduced anxiety, erythema, and cortisol levels on post-operative day 1

Broadbent et al. [85]

Raghuram et al. [86]

Holden-lund et al. [87]

Acute and chronic


Evaluated the effect of hypnosis on wound healing.

Evaluated the effect of hypnosis on wound healing in patients that had a bilateral symmetric burn wound where only one side was treated.

Evaluated the levels of CD3+– and CD4+ T-lymphocytes, and interleukin-1 production at two different stress states, with and without hypnosis intervention.

Evaluated hypnosis and pain

Found that wound healing occurred at a faster rate in patients who underwent targeted hypnosis intervention.

Four out of five patients showed accelerated healing on the treated side. The 5th patient showed equal healing on both sides.

Showed an increase of CD3+– and CD4+ T-lymphocytes with the use of hypnosis. Hypnosis could have a beneficial effect on the immunological dysregulation from acute stress.

Hypnosis was shown to decrease pain during wound debridement and thus could be used to decrease patient distress

Ginandes et al. [88]

Moore and Kaplan [89]

Kiecolt-Glaser et al. [90]

Patterson et al. [91]

Acute and chronic

Cognitive-behavioral stress management (CBSM)

Evaluated cognitive-behavioral stress management (CBSM) therapy in patients with stage I and II breast cancer.

Evaluated CBSM therapy in patients with prostate cancer.

Evaluated pro-inflammatory leukocyte gene expression in patients receiving 10 weeks of CBSM therapy

Patients receiving CBSM showed a decrease in cortisol levels in comparison to the control group.

CBSM was shown to improve the quality of life in patients with prostate cancer.

CBSM was shown to reverse upregulation of gene expression

Cruess et al. [93]

Penedo et al. [94]

Antoni et al. [95]


Stress impacts the immune system, surgical outcomes, metabolism, as well as risks of various diseases including obesity and cardiovascular disease. The skin is the largest organ of the human body. It is vital for fluid balance, thermoregulation, Vitamin D production, as well as protection from pathogens and mechanical injury. Wounds occur when there is a disruption in the anatomic and physiologic continuity of the skin. As aforementioned, wounds can be classified as acute or chronic, depending on the time course of healing; according to etiology, including, but not limited to, venous insufficiency, arterial disease, autoimmune disorders, pressure, diabetes and neuropathy, trauma, surgery, and burns; or by location (lower extremity, foot, etc.). Maintenance of skin integrity and timely wound healing is critical. When this process is disrupted, chronic wounds result, bringing about a large physical, psychological, and economic burden to the patient. Chronic stress impairs proper wound healing, alters immune function, and is associated with worse surgical outcomes, therefore it is necessary to address stress reduction as part of the treatment plan for patients with wounds.



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Sep 16, 2017 | Posted by in Dermatology | Comments Off on Stress and Wound Healing
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