The Impact of
on Wound Healing:
Jean-Philippe Gouin, MAa,b,*, Janice K. Kiecolt-Glaser, PhDa,b,c
Wound healing is a critical process involved in the recovery from injury and surgical
procedures. Poor healing increases the risk for wound infections or complications,
lengthens hospital stays, magnifies patient discomfort, and slows return to activities
of daily living. Converging evidence from different research paradigms suggests
that psychological stress and other behavioral factors can affect wound healing. A
meta-analytical study using diverse wound-healing models and outcomes found
that across studies there was an average correlation of ?0.42 between psychological
stress and wound healing.1This result suggests that the relationship between stress
and wound repair is not only statistically significant but also clinically relevant. This
review presents data and methods from observational, experimental, and interven-
tional studies corroborating the impact of stress on wound healing. Potential behav-
ioral and physiologic mechanisms explaining the association between stress and
impaired wound healing are also discussed.
Work on this article was supported by a doctoral research training award from the Fonds de la
Recherche en Sante ´ du Que ´bec and NIH grants AG029562, CA126857, CA131029, AT003912,
Ohio State Comprehensive Cancer Center Core Grant CA16058, and NCRR Grant UL1RR025755.
aDepartment of Psychology, The Ohio State University, 225 Psychology Building, 1835 Neil
Avenue, Columbus, OH 43210, USA
bInstitute for Behavioral Medicine Research, The Ohio State University College of Medicine,
460 Medical Center Drive, Room 139, Columbus, OH 43210-1228, USA
cDepartment of Psychiatry, The Ohio State University College of Medicine, 1670 Upham Drive,
Columbus, OH 43210, USA
* Corresponding author. Institute for Behavioral Medicine Research, The Ohio State University
College of Medicine, 460 Medical Center Drive, Room 139, Columbus, OH 43210-1228.
E-mail address: Gouin.email@example.com
? Wound healing ? Stress ? Cytokine ? Cortisol
Immunol Allergy Clin N Am 31 (2011) 81–93
0889-8561/11/$ – see front matter ? 2011 Elsevier Inc. All rights reserved.
Prospective studies examining wound healing–related complications following
surgery provide evidence for the impact of stress on wound repair. Greater fear or
distress before surgery has been associated with poorer outcomes including longer
hospital stays, more postoperative complications, and higher rates of rehospitaliza-
tion.2,3For example, among 111 patients undergoing gallstone removal surgery, those
who reported more stress on the third postoperative day had a longer hospital stay,
compared with less anxious individuals.4Among 309 consenting consecutive patients
who underwent an elective coronary artery bypass graft surgery, patients who were
more optimistic were less likely to be re-hospitalized than less optimistic individuals.
Conversely, patients who experienced more depressive symptoms were more likely
to require rehospitalization for infection-related complications than individuals report-
ing less distress.5This result was replicated in a study of 72 patients undergoing coro-
nary artery bypass surgery. Patient who had more depressive symptoms at discharge
had more infections and poorer wound healing in the following 6 weeks after surgery
than participants who reported less distress.6
Psychological factors can also modulate healing of chronic wounds. Fifty-three
older adults with chronic lower leg wounds were followed longitudinally to assess
speed of wound repair. Patients who experienced the highest levels of depression
and anxiety (based on a median split of the Hospital Anxiety and Depression Scale)
were 4 times more likely to be categorized in the delayed healing group than individ-
uals who reported less distress.7Of importance, in these observational studies
distress predicted wound-healing outcomes over and above differences in sociode-
mographic variables and medical status. Psychological distress thus appears to influ-
ence recovery from medical procedures and healing of chronic wounds in clinical
Animal and human studies in which standard wounds are created experimentally and
healing is closely monitored over time provide the strongest evidence of the impact of
stress on wound repair. Three main wounding methodologies have been used to study
the effect of stress on wound healing.
Punch Biopsy Model
Punch biopsies are used to create standard full-thickness dermal wounds as well as
mucosal wounds. Daily pictures of the wound allow for a quantification of changes in
wound size over time.
The first human experimental study that examined the impact of stress on wound
healing involved family dementia caregivers. Caregivers have to deal daily with the
loss of memory, inappropriate emotions, and wandering and restless behavior of their
loved ones. Caregiving stress has been associated with heightened anxiety and
depression, immune dysregulation, increased risk for cardiovascular disorders, and
even death.8Family dementia caregiving thus represents an excellent model of
chronic stress in humans. A 3.5-mm punch biopsy wound was created on the
nondominant forearm of 13 women caregivers and 13 sociodemographically similar
noncaregiving controls. Caregivers took 24% longer to heal the small, standardized
dermal wound than matched controls, providing initial evidence that chronic stress
can delay wound repair.9
Stress can also impede healing of a punch biopsy wound among younger people
who experienced less intense stress. Twenty-four healthy young men were followed
Gouin & Kiecolt-Glaser
for 21 days after a standard 4-mm punch biopsy was performed on their forearm. In
that study, wound healing was assessed using ultrasound biomicroscopy. Stress
levels were measured using a self-report questionnaire, the Perceived Stress Scale.
Higher perceived stress on the day of the biopsy was associated with slower wound
healing.10A substantial correlation of ?0.59 was found between perceived stress and
healing progress between the days 7 and 21 after the biopsy.10
Pain, a physical and psychological stressor, can also influence wound healing. A
2-mm full-thickness wound was placed on the back of one upper arm of obese women
before receiving elective gastric bypass surgery. Greater acute pain immediately after
surgery and persistent pain in the 4 weeks following surgery were associated with
slower healing of the experimental wound.11Pain generates psychological distress
and, when compounded by the presence of other stressors, can put a person at
increased risk for delayed wound repair.12
Well-controlled animal studies corroborate the impact of stress on wound healing
observed in humans. Mice subjected to restraint stress healed a standardized 3.5-mm
full-thickness punch biopsy wound on average of 27% more slowly than control
mice who were not exposed to the stressor.13Restraint stress was also associated
with delayed wound healing in a reptilian species, Urosaurus ornatus (tree lizard).14
Social stressors can also impair wound healing. Monogamous California mice, Pero-
myscus californicus, healed a punch biopsy wound more slowly when stressed by the
separation from their conspecifics, compared with when they were continuously
housed with their conspecifics.15
Like cutaneous wounds, mucosal wound healing isalso responsive to psychological
stress, as demonstrated by a study with academic examination stress. Using a within-
subject design, 11 dental students had a biopsy performed on their hard palate during
their summer vacation and again 3 days before a major examination. Mucosal wounds
placed before the examination healed on average 40% more slowly than identical
wounds made during summer vacation. Of importance, the differences in the rate of
healing were very consistent: no student healed as rapidly during examinations as
The impact of negative emotions on mucosal wound healing was replicated in
a larger study. Among 193 healthy undergraduate students who received a 3.5-mm
wound on the hard palate, individuals reporting high levels of depressive symptoms
were almost 3.6 times more likely to be classified as slow healers than less dysphoric
Blister Wounds Model
The blister wounds model is another experimental paradigm designed to study the
impact of psychological factors on wound healing. Blister wounds are produced by
the application of a vacuum pump on the forearm. A gentle suction creates a separa-
tion of the epidermis from the dermis over the course of 1 hour. One of the strengths of
this method is that it allows for the collection of data on cytokine production at the
wound site, as described below. In this model, wound healing is assessed via
measurement of the rate of transepidermal water loss (TEWL). One of the main func-
tions of the skin is to limit movement of water in and out of the body. The permeability
of the epidermis increases after the blister wound, but decreases as the healing
process unfolds. A computerized evaporimetry instrument can measure vapor pres-
sure gradient in the air layers close to the skin surface. TEWL measurement is a nonin-
vasive means to monitor changes in the stratum corneum barrier function of the skin
that provides an excellent objective method for the evaluation of wound healing.
Impact of Psychological Stress on Wound Healing
Using a blister wounds paradigm, the discussion of a marital disagreement,
a commonplace stressor, delayed wound repair. Married couples were invited for
two 24-hour admissions at a hospital research unit. During both visits, 8 8-mm suction
blisters were created on the participants’ nondominant forearm. Wound healing was
monitored for 14 days using TEWL measurements. During the first admission, couples
participated in a structured social support interaction task. During the second visit,
couples were asked to discuss marital disagreements during a 30-minute period. After
both interaction tasks, couples remained in the research unit until the next morning to
allow for cytokine measurements and to minimize external influences on wound
Couples’ blister wounds healed more slowly following the marital conflict visit than
after the social support visit, suggesting that the stress induced by the discussion of
marital disagreements interfered with wound repair. Furthermore, the quality of the
discussion also influenced the rate of healing. Couples who had more hostile and
negative interactions across both the support and the conflict discussions healed
wounds more slowly than couples whose interactions were less negative. The overall
differences related to hostility were substantial. The blister wounds in high hostile
couples healed at only 60% of the rate of low hostile couples.18
In a different subset of participants from the same study, positive behaviors during
the social support task were also related to wound repair. Individuals who displayed
more self-disclosure, acceptance of their partner, relationship-enhancing statements,
and humor during the interaction task healed the blister wounds faster than partici-
pants who exhibited less positive behaviors during the marital interaction task.19
Difficulties in managing one’s anger has also been associated with impaired wound
healing. Blister wounds were created on the forearm of 98 community-dwelling partic-
ipants who were followed for 14 days to monitor healing speed. Anger management
styles were assessed via a self-report questionnaire, the Spielberger Anger Expres-
sion Scale. Participants who had difficulty controlling the expression of their anger
were 4.2 times more likely to be classified as slow healers than individuals who
reported better anger control. Furthermore, individuals with anger management issues
secreted more cortisol in response to the blistering procedure. The increased gluco-
corticoid production was in turn related to delayed healing.20
Tape Stripping to Disrupt Skin Barrier Function
Another wound-healing model consists of the repeated application of cellophane tape
to remove a layer of epidermis cells, causing a disruption of the stratum corneum
barrier function of the skin. This procedure affects epidermal permeability. Wound
healing is assessed by measuring the rate of recovery of the skin barrier function using
Acute laboratory stressors can delay the recovery of skin barrier function following
its disruption by tape stripping. Twenty-five women participated in the Trier Social
Stress Test (TSST), a psychosical stressor.21The TSST, a standardized laboratory
stressor with a mock job interview and a mental arithmetic task, induces reliable
changes in heart rate, and cortisol and cytokine production, and subjective anxiety
responses.22,23Skin barrier repair was delayed in women after the TSST as compared
with a stress-free period.21
This result was replicated in a larger study of 85 healthy young men and women.
Individuals who participated in the TSST had a slower recovery of skin barrier function
than participants who engaged in a reading control task.24Furthermore, positive affect
had a protective effect on stress-induced delays in skin barrier recovery. Stressed
Gouin & Kiecolt-Glaser
individuals reporting more positive affect recovered faster from the tape-stripping
procedure than stressed participants who had low-trait positive affect.25
Academic examination stress affects skin barrier recovery. Twenty-seven profes-
sional and medical students underwent a tape stripping procedure on 3 occasions:
right after their winter and spring vacations, and during their winter final examination
week. Skin barrier recovery was significantly delayed at 3, 6, and 24 hours after
tape stripping during the examination period, compared with the 2 vacation periods.
Furthermore, students reporting the most stress during the examination period had
slower recovery in skin barrier function than participants who experienced less exam-
The interpersonal stress associated with the dissolution of a committed marital rela-
tionship can impede recovery of the stratum corneum barrier function of the skin.
Twenty-eight women who were going through adivorce or a separation and27 women
who reported high levels of marital satisfaction underwent a tape-stripping procedure
on both facial cheeks. Socially stressed women had delayed skin barrier recovery at 3
and 24 hours following the tape-stripping procedure, compared with less stressed
In animal models, different types of stressors can also impair skin barrier recovery.
Three days of immobilization stress delayed skin barrier function recovery even for 7
days, compared with control rats not exposed to the stressor.28Social reorganization
stress associated with cage transfer also impaired the restoration of skin barrier func-
tion in rats.29These results converge with human data indicating that psychological
stress can disrupt skin barrier recovery.
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 manage-
ment interventions before surgery have been associated with improved postoperative
outcomes, including fewer medical complications and shorter hospital stays.30,31
Written emotional disclosure interventions can decrease psychological distress,
improve self-reported health, enhance aspects of cellular immunity, and decrease
health care use.32Men were randomized to a written emotional disclosure intervention
or a nonintervention control group, and received a punch biopsy on the nondominant
forearm. Healing was assessed using ultrasound biomicroscopy on 3 occasions
during a 21-day period. Men who participated in the emotional disclosure intervention
had smaller wounds than control participants at 14 and 21 days.33
Physical exercise can reduce psychological distress in addition to improving cardio-
vascular function.34Older adults were randomized to an exercise intervention (1-hour
aerobic exercise session, 3 times per week) or a nonintervention 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.35In 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.37In animal studies,
monogamous rodents who were housed in pairs healed a standard punch biopsy
wound faster than rodents housed alone.38Pair 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
Impact of Psychological Stress on Wound Healing
These data indicate that the presence of a familial conspecific improves wound-
healing outcomes in monogamous rodents.
A pharmacologic agent commonly used in the treatment of mood and anxiety disor-
ders is fluoxetine.40In a study usingalternating isolation andcrowding stress, stressed
Wistar rats who received fluoxetine healed at a similar pace as their nonstress coun-
terparts, and faster than stressed animals who received only a vehicle injection.41
These results indicate that pharmacologic stress reduction may also improve wound
In summary, a wide array of acute and chronic stressors can disrupt the healing
process. Furthermore, the impact ofstress on wound repair has been observed across
different methodologies and with different healing outcomes, and most results have
replicated in at least 2 independent laboratories. Results from observation, experi-
mental, and intervention studies collectively provide strong evidence that psycholog-
ical stress can influence wound healing.
BIOLOGY OF WOUND HEALING
A brief review of the biology of wound healing is presented to highlight the pathways
by which psychological stress can impede the repair process. Wound healing prog-
resses through several overlapping stages.42In the initial inflammatory stage, vaso-
constriction and blood coagulation are followed by platelet activation and the
release of platelet-derived growth factors (PDGFs) as well as chemoattractant factors
released by injured parenchymal cells. Cytokines and chemokines, such as interleukin
(IL)-1a, IL-1b, transforming growth factor-b (TGF-b), vascular endothelial growth
factor, tumor necrosis factor-a (TNF-a), and IL-8 play important roles in the early stage
of wound healing. These factors act as chemoattractants for the migration of phago-
cytes and other cells to the site, starting the proliferative phase that involves the
recruitment and replication of cells necessary for tissue regeneration and capillary
regrowth. The final step, wound remodeling, may continue for weeks or months.
Thus, the healing process is a cascade, and success in the later stages of wound
repair is highly dependent on initial events.42
Inflammation plays a key role early in this cascade, and proinflammatory cytokines
are essential to this effort; they help to protect against infection and prepare injured
tissue for repair by enhancing the recruitment and activation of phagocytes.43Further-
more, cytokines released by recruited cells regulate the ability of fibroblasts and
epithelial cells to remodel the damaged tissue.43IL-1 produced early after tissue injury
can regulate the production, release, and activation of metalloproteinases that are
important in the destruction and remodeling of the wound; IL-1 also regulates fibro-
blast chemotaxis and the production of collagen.43Moreover, IL-1 stimulates the
production of other cytokines that are important for wound healing, including IL-2,
IL-6, and IL-8.43Confirming the importance of proinflammatory cytokines in the heal-
ing process, IL-6 knock-out mice healed a standard wound 3 times more slowly than
wild-type mice.44Accordingly, deficits early in the wound repair cascade can have
adverse downstream consequences.
PHYSIOLOGIC PATHWAYS OF THE STRESS-INDUCED WOUND-HEALING IMPAIRMENT
Psychological stress leads to the activation of the hypothalamic-pituitary-adrenal and
the sympathetic-adrenal-medullary axes.45Enhanced glucocorticoids and catechol-
amines production can directly influence several components of the healing process.
Substantial evidence from animal and humans studies indicate that physiologic stress
responses can retard the initial inflammatory phase of wound healing.46Fig. 1
Gouin & Kiecolt-Glaser
presents a schematic representation of the behavioral and physiologic pathways link-
ing stress and wound healing.
Stress-induced glucocorticoid production has been associated with delayed wound
healing. In humans, greater awakening cortisol secretion the day following a punch
biopsy was associated with greater perceived stress and delayed wound healing.10
In animal studies, restraint stress led to a fourfold elevation in corticosterone levels.13
Blocking glucocorticoid function with a glucocorticoid receptor antagonist, RU40555,
eliminated the stress-induced delay in wound healing in stressed animals.13,39Pre-
venting glucocorticoid production via adrenalectomy also reduced the effects of
restraint stress on wound healing.39Furthermore, exogenous administration of gluco-
corticoid slowed wound healing as compared with a vehicle injection.13
Increased catecholamine production also appears to play a role in stress-induced
impairment in wound healing. Administration of an a-adrenergic receptor antagonist
attenuated the restraint stress-induced impairment of wound healing in mice.47In
a study using a rotation stress model, administration of a b-adrenergic receptor antag-
onist, propranolol hydrochloride, attenuated the stress-induced impairment in wound
healing in mice.48In a burn wound model, mice injected with a b-adrenergic receptor
antagonist exhibited improved reepithelialization of burn wounds, compared with
mice who received a vehicle injection.49Furthermore, injection of norepinephrine
can reduce keratinocyte motility and migration in vitro.49These data provide evidence
of a role for catecholamines in stress-induced impairment in wound repair.
Oxytocin and Vasopressin
The two hypothalamic peptides, oxytocin and vasopressin, modulated physiologic
stress responses and social bonding processes in animal and human work. In
a couples study using the blister wounds model, individuals who had more positive
interactions with their partner during a social support task had higher plasma oxytocin
levels. Higher circulating oxytocin levels were in turn associated with faster healing of
the standard blister wounds. Furthermore, in women, but not in men, greater plasma
vasopressin levels were related to faster healing.19
Well-controlled animal studies corroborate the role of oxytocin in mediating the
beneficial effects of social relationships on wound healing. Exogenous oxytocin
Fig. 1. Behavioral and physiologic pathways linking psychological stress and wound healing.
Impact of Psychological Stress on Wound Healing
administration attenuated the stress-induced corticosterone production and impair-
ment in wound healing.39,50Furthermore, administration of an oxytocin receptor
antagonist eliminated the beneficial impact of pair housing on wound healing.39These
results collectively suggest that in addition to modulating stress responses, oxytocin
may have a direct influence on the healing process.
Local Cytokine Production
Diminished expression of proinflammatory cytokines at the wound site is another
pathway by which stress can delay the initial phase of wound healing. The suction
blister model provides a method to monitor in vivo cytokine expression at the wound
site in humans. After raising several blisters and removing their roofs (the epidermis),
plastic templates with wells containing a salt solution and autologous serum are
placed over the lesions to monitor protein expression at the wound site. The autolo-
gous serum-buffer solution is aspirated from the wells with a syringe at different
time intervals, allowing for cell phenotyping and cytokine measurement as the local
immune response evolves.
Using this approach, women who reported more perceived stress produced signif-
icantly lower IL-1a and IL-8 levels at the wound site, 5 and 24 hours after the blistering
procedure.51Marital disagreement also influenced local cytokine production.18
Production of three proinflammatory cytokines at the wound site, IL-1b, IL-6, and
TNF-a, were lower after the discussion of a marital disagreement than after a social
support discussion, paralleling the impact of marital conflict on wound healing.18In
these two studies, local cytokine production was not significantly associated with
serum levels of the same cytokines, underscoring the different biologic significance
of local and systemic production of these molecules.
In a clinical study, patients undergoing surgery for hernia removal who reported
greater preoperative stress had a lower concentration of IL-1b in the wound drain fluid
20 hours after the operation, compared with patients who experienced less preoper-
ative distress.52Furthermore, two stressors that can impair cutaneous and mucosal
wound healing, family dementia caregiving and academic examinations, were also
associated with poorer stimulated production of IL-1b after treatment with lipopoly-
saccharide.9,16Corroborating human data, mice subjected to restraint stress had
lower levels of IL-1b mRNA at the wound site, compared with control mice.53,54
Stress-induced glucocorticoid production might effectively decrease cytokine
production at the wound site. Exogenous administration of glucocorticoid diminished
IL-1a, IL-1b, and TNF-a expression at the site after wounding in mice.42Similarly,
animal and human studies have also demonstrated that stress-induced elevations in
glucocorticoids can transiently suppress IL-1b, TNF-a, and PDGF production.51,54
Accordingly, dysregulation of glucocorticoid secretion provides one obvious neuroen-
docrine pathway through which stress alters the initial inflammatory phase of wound
Matrix metalloproteinase (MMP) enzymes are involved in the degradation of collagen
and other extracellular matrix molecules. Degradation of the basement membrane of
the wound promotes cellular invasion and migration, an essential component of the
early phase of wound healing. Among patients undergoing inguinal hernia surgery,
those who reported greater worry about the operation had lower levels of MMP-9 in
the wound drain fluid 20 hours after surgery.52In a human study using the blister
wounds model, there was a negative correlation between plasma cortisol levels and
MMP-2 protein levels at the wound site.55Furthermore, in an animal study using
Gouin & Kiecolt-Glaser
a rotation stress model, mice subjected to the stressor had fewer activated MMP-2
and MMP-9 7 days after wounding, compared with control mice.48These data indi-
cate that stress can downregulate MMP production at the wound site.
Psychological stress may reduce cell infiltration at the wound site. In a study using
a restraint stress paradigm, cellularity of the wound and wound margin areas were
analyzed in cross sections of dermal and epidermal layers. Mice subjected to restraint
stress had less leukocyte infiltration to the wound sites than control mice at 1 and 3
days after wounding.13
Increased Susceptibility to Infection
Stress can also increase susceptibility to wound infection. Mice exposed to restraint
stress had a 2- to 5-log increase in opportunistic bacteria such as Staphylococcus
aureus, compared with control mice not exposed to the stressor. Furthermore, 7
days after wounding, 85.4% of restraint-stress mice had bacterial counts predictive
of infection, compared with 27.4% of controls.56
The increased susceptibility to infection appears to be mediated in part by
a decreased epidermal antimicrobial peptides production. Mice exposed to insomnia
and crowding stress had lower epidermis levels of cathelin-related antimicrobial
peptides and exhibited more severe infection following an intradermal injection of
group A Streptococcus pyogenes.57This effect appears to be glucocorticoid depen-
dent; administration of a glucocorticoid receptor antagonist eliminated the impact of
stress on epidermis antimicrobial peptide production, and administration of exoge-
nous glucocorticoid mimicked the effects of stress on antimicrobial production.57
Oxygen homeostasis is critical to all phases of wound healing. Damage created to
blood vessels during wounding decreases oxygen availability. Simultaneously, neutro-
phils’ oxidative burst increases oxygen demand at the wound site. Restraint stress can
further promote wound hypoxia.58Compared with controls, restraint-stressed mice
had higher levels of inducible nitric oxide synthase levels, an indicator of wound
hypoxia at the wound site.58Furthermore, hyperbaric oxygen therapy normalized
inducible nitric oxide synthase levels and attenuated stress-induced impairments in
BEHAVIORAL MECHANISMS LINKING STRESS AND WOUND HEALING
In addition to directly modulating physiologic responses to skin damage, stress can
also indirectly influence wound repair by promoting the adoption of health-damaging
behaviors. Individuals who experience greater levels of stress are more likely to
increase their alcohol and tobacco use, decrease their participation in physical
activity, experience sleep disturbances, and make poorer diet choices than individuals
reporting less distress.59,60These negative health behavior practices can then
compound the detrimental impact of stress on physiologic healing processes.2
Heavy alcohol use has been associated with delays in cell migration and collagen
deposition at the wound site, which in turn can impede the healing process.61
Smoking has also been related to slowed healing of naturally occurring and surgical
wounds.62Sleep disruption delays skin barrier recovery after tape stripping and dimin-
ishes growth hormone production.21,63Lack of regular physical activity can slow the
Impact of Psychological Stress on Wound Healing
rate of wound healing.36Furthermore, deficient intake of glucose, polyunsaturated
proteins, and certain vitamins can impede the healing process.64–66
The goal of this review is to present clinical and experimental models of the impact of
stress on wound repair. Converging and replicated evidence from experimental and
clinical models of wound healing indicates that psychological stress leads to clinically
relevant delays in wound healing. New mechanistic data suggest ways to elucidate the
multiple physiologic pathways by which stress alters wound repair processes. Trans-
lational work should focus on identifying conditions in which behavioral and pharma-
cologic treatments are the most effective and on developing new treatments able to
attenuate stress-induced delays in wound healing.
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