Ulysse Pereira

Experimental Models of Itch

Pruritus can be defined as an unpleasant cutaneous sensation that leads to the need to scratch. This “umbrella definition” was proposed more than 360 years ago by the German physician Samuel Hafenreffer and does not describe the complexity of this phenomenon. Activation and control of pruritus may occur at different levels of the skin-brain connection1 like pruritoceptive itch, neurogenic itch, neuropathic itch and psychogenic itch. Because they are different types of pruritus, it is impossible to develop a “universal model of pruritus” and so, different categories of models, according to the purpose of the study, are available. It is obvious that no model is perfect. Each model exhibits advantages for a particular kind of study, and is also restricted by limitations that impede its use in other studies.

In vitro models to study cutaneous innervation mechanisms

The skin is densely innervated to transmit all sensations (touch, temperature, pressure, pain, and pruritus) but not only it. Indeed, innervation plays a major role in the structuration of the epidermis, in its renewal, and in the process as wound healing. There are increasing evidences that skin cells and cutaneous nerve endings are in close interactions each other. So, to study them is an important issue to better understand the behavior of the skin and its both physiological and pathological processes. However, due to scientific, technical, ethical, or economic reasons, the study of these interactions in human or animals in vivo remains quite impossible. So, the development of in vitro models is crucial to better understand them. Since several years, all the actors of these interactions, skin cells such as keratinocytes, fibroblasts, melanocytes, Merkel cells or stem cells, and sensory neurons, could be extracted and cultured independently or together so named 2-D cocultures. Other cocultures, the 3-D cocultures, could also be considered by the use of the epidermis or dermis or whole portions of native or reconstructed skin. These 3-D models offer also an alternative by the use of compartmented cocultures to only analyze the biochemical communication between the different types of cells. After a description of the different models available, this chapter will give some clues to define the best model(s) depending of the applications and, finally, will discuss of the advantages and the limitations of these types of cultures to study cutaneous innervation mechanisms.