Laurent Misery


Expert Rev Dermatol. 2013;8(6):631-637. 

In This Article


Histological examination rarely shows vasodilatation with an inflammatory infiltrate. In general, there are no histological abnormalities. The usual absence of an infiltrate demonstrates that there is no role for innate or specific immunity. Skin sensitivity is more frequently reported by patients with atopic dermatitis or other allergic conditions,[3] but most people with sensitive skin do not have atopy of allergic disease.

Skin barrier function is altered in certain patients, leading to TEWL that may promote contact with triggering factors.[20] Nonetheless, altered barrier function is not found in all people with sensitive skin, suggesting that sensitive skin and dry skin are different phenomena. A relationship is not excluded because skin dryness and alterations in the skin barrier could favor skin sensitivity by facilitating contact with triggering factors. Alternatively, skin sensitivity could favor skin dryness. Skin dryness and skin sensitivity could also be consequences of the same pathogenic mechanism when the two conditions are associated. The regular use of skin moisturizers seems to improve skin sensitivity.[21]

Abnormal sensations and vasodilatation reflect the involvement of the cutaneous nervous system.[9] Neurotransmitters, such as substance P, calcitonin gene-related peptide (CGRP)[22] and vasoactive intestinal peptide (VIP) may induce neurogenic inflammation with vasodilatation and mast cell degranulation. Neurogenic inflammation is defined by the release of neuropeptides (by nerve endings) that induces inflammation.

A fascinating and mysterious aspect of sensitive skin is the triggering by factors that are very heterogeneous. Although it has never been demonstrated, the role of transient receptor potential (TRP) channels in skin reactivity is obvious. Sensitive skin is defined as a response to multiple factors that may be physical and/or chemical, and TRP channels are the only molecules that could be activated by these particularly different factors. The abnormal or enhanced activation of TRP channels appears highly probable.[9] In the skin, TRP channels are expressed on nerve endings, Merkel cells and keratinocytes.[23] TRPV1 is activated by capsaicin, phorbol esters, heat and H + ions. TRPV3 is activated by heat and camphor. TRPV4 activation is due to heat, mechanical stresses, hypo-osmotic stress and phorbol ester derivatives. Cold and menthol activate TRPM8. TRPA1 is activated by cold, wasabi, mustard, horseradish and bradykinin. TRP channels are most likely activated by other substances that are included in cosmetic products. The activation of TRP channels is followed by Ca2+ influx into cells and then depolarization. Interestingly, the activation of TRPV4 on keratinocytes induces alterations in the skin barrier.[24]

In summary, it is probable that epidermal TRP channels are overstimulated by various factors in sensitive skin or are overexpressed. Consequently, there is a release of neurotrophins and neurotransmitters, which induce neurogenic inflammation in the skin.

Skin explants are useful models for dermatological research,[25] and the explants' co-culture with neurons[26] could be a very interesting in vitro model for studies on sensitive skin. A co-culture of neurons and keratinocytes is also a valuable model for in vitro studies on sensitive skin.[27] Cells from a neuronal cell line could also be co-cultured with keratinocytes.[28] In these models, neurogenic inflammation could be measured based on the release of neuropeptides or the electrical activity. The soothing effects of substances that are used in cosmetics could be measured.[29]

Functional MRI was used to evaluate the neural reaction to the application of lactic acid on the faces of women with and without sensitive skin.[30] Lactic acid-induced skin discomfort resulted in increased activity in the primary sensorimotor cortex contralateral to the application site and in the bilateral frontoparietal network. In sensitive-skin patients only, group activity spread into the ipsilateral primary sensorimotor cortex and the bilateral peri-insular secondary somatosensory area. These subjects also had great increases in neural activity. These results suggest an involvement of the central nervous system and allow an understanding of the role of stress in sensitive skin.

Hence, the pathophysiology of skin sensitivity remains poorly understood because of difficulties to define and diagnose the condition and because sensitive skin might be a heterogeneous phenomenon.[31] Sensitive skin is an exaggeration of physiological reactions, with a key role for the nervous system. In sensitive skin, the 'skin tolerance threshold' is abnormally low.