The process of wound healing can be divided into three main processes: inflammation, proliferation, and remodeling.

Inflammation starts when disruptions of capillary blood vessels start the induction of the hemostatic cascade. The leaked intra- vascular contents form fibrin clots. Platelets degranulation releases enzymes and cytokines that recruit cells such as fibroblasts.

The second stage in wound healing is proliferation, which begins around day 4 or 5 with the migration of fibroblasts into the wound matrix. The fibroblasts synthetize extracellular matrix (ECM), which paves the way for migration of various cells that collaborate in the wound healing process.

Wound contraction usually begins around day 10 to 12. Myofibroblasts, which contain actin filaments, help to initiate wound contraction.

By 2–4 weeks, the fibroblasts replace the fibrin with a more robust matrix of collagen fibers. In the mature wound, the initial elastic fiber network is no longer observed and explains the firmness and absence of elasticity of scars.

The third and last stage in wound healing is the remodeling phase, which usually begins 3 weeks after tissue injury. Microscopic findings of this stage include decreases in fibroblast count, occlusion of blood vessels, and hardening of collagen fibers (transformation from collagen type III to type I).

Continuous collagen production and degradation has an effect of remodeling the mature wound matrix for approximately 6 months post injury. At this point, production and degradation balances each other, and no significant change in collagen amount is observed. The remodeling phase is the most responsible for intra and interpersonal variations in scar qualities. A wound can become an unsightly scar during this period.

These phases are not distinct, but intertwined. The whole healing process is a continuum of this three processes occurring at the same time [10, 21].

There are different types of stress. Stress can be chronic, acute, sequenced, distant, actual or perceived.

Actual stress involves things that have a direct effect on the subject, which includes environmental stress (air, water and noise pollution), harming behaviors (smoking, drinking, diets, lack of sleep) and even psychological stress (issues related to relationships, job, financial, and others). On the other hand, perceived stress are the feelings or thoughts that an individual has about how much stress they are under at a given point in time or over a given time period. It is result of the interaction between the individual and his or her environment, and this assessment is influenced by traits such as personality, coping resources, and social support [19].

In addition, the question is: Would there be a difference in the healing process and therefore formation of unaesthetic scars or keloids if the person were experiencing actual stress or perceived stress? To correctly answer this question is important to keep in mind that actual and perceived stress are not directly proportional. Sometimes, people with high perceived stress have low actual stress levels. But perceived stress raises cortisol levels just as the actual stress does.

Burns et al. [3] evaluated the immune response to a vaccine, and found that high perceived stress, but not life events stress (actual stress), was associated with low antibody titers (low immunity) [3].

In addition to directly modulating physiological 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, compared to individuals reporting less distress. These negative health behavior practices can then compound the detrimental impact of stress on physiological healing processes [11].

The skin is actually considered part of the Neuro-Immune-Endocrine System, establishing a bidirectional communication: from periphery (skin) to central (central nervous system) and vice-versa (Table 7.1).

There are two important axis: (1) the skin has an equivalent to the Hypothalamus-pituitary-adrenal (HPA) axis, which coordinates stress responses with the central HPA axis. The activity of the HPA axis is governed by the production of Corticotrophin releasing hormone (CRH) by the Hypothalamus, which on your turn activate the secretion of Adrenocorticotropic hormone (ACTH) by the Pituitary gland. The ACTH stimulates the secretion of steroids by the Adrenal cortex. (2) Since the skin is highly innervated with sensory nerves derived from the dorsal root ganglion, it forms a direct path between skin and the adrenal glands, the(Sympathetic-Adrenal-Medullary axis). This system mediates the main adaptive response to systemic stress, either external or internal. In the skin, it protects against stressors such as the UV radiation and pathogens.

Skin reactions to stress can range from itching and pain (which are well known as psychodermatosis, induced by neurotrophins and neuropeptides) sweating (that can cause alteration of skin conductance and impedance, which alters patterns of migration of cells to injured areas), and affected barrier function by alteration of permeability homeostasis and can facilitate infection (induced by increased levels of glucocorticoids which inhibit epidermal lipid synthesis). All these factors can alter the process of wound healing [1, 7, 13, 20].

Many studies show that psychological stress can affect the skin, for example in diseases such as psoriasis, atopic dermatitis and urticaria. Studies performed in animal models showed that psychological stress induced by insomnia, over-crowding, and noise affect the wound healing process [1, 5]. A few prospective studies were conducted in humans to evaluate the effect of the stress in the wound healing (Table 7.2).