Activation of primary sensory neurons by the topical application of capsaicin on the epidermis of a re‐innervated organotypic human skin model

Abstract

Using an ex vivo skin-nerve preparation, skin and nerve cells were reconstituted into a single unit and maintained in a nutrient medium bath until required experimentally. Our objective was to use the epidermis as a relay for the induction of an electric current to the neurons following the topical application of capsaicin on the skin epidermis of the skin explant, an agonist of the TRPV1 channel implicated in pruritus and pain. After 10-20 days of coculture to form the re-innervated skin model, we applied a solution of capsaicin directly on the epidermis of the skin explant (4 lM). The resulting current was recorded using a path-clamp technique on the neuronal fibres. Following the topical application of capsaicin, spontaneous activity was triggered, as characterised by repetitive spikes with periods of 125, 225 or 275 ms. This study demonstrates that the skin explant and nerve cells preparation may receive stimuli and be used to screen molecules or to study signal transmission.

Sensitive Skins May Be Neuropathic Disorders: Lessons from Studies on Skin and Other Organs

“…The reinnervation of human skin explants with DRG neurons is a very satisfying model for sensitive skin [74,75]. In this model, it is possible to activate sensory neurons after the application of capsaicin on the epidermis, as showed by the modification of electric currents on patched nerve fibres and the release of neurotransmitters [76]. For the screening of putative active substances for sensitive skin, it is more convenient to use a co-culture of keratinocytes and neurons, which can be also activated by capsaicin or lactic acid [77].…”

Modélisation tridimensionnelle in vitro des systèmes nerveux et immunitaire de la peau

“…On peut ainsi s'attendre à ce que, en fonction de l'agoniste choisi et de sa concentration, les proportions des neuropeptides libérés soient différentes. Il est possible de ré-innerver des explants de peau [12,32]. Toutefois, cette procédure, difficilement applicable à des biopsies provenant de patients, ne permet pas de moduler la composition cellulaire de l'explant et ne garantit pas l'élimination des cellules immunitaires cutanées et des fibres nerveuses du donneur (sectionnées lors de la biopsie), et dont les éléments qui subsistent après prélèvement sont susceptibles d'affecter la réponse du modèle.…”

What about physical contacts between epidermal keratinocytes and sensory neurons?

“…Indeed, after discussions for many years, it has been clearly demonstrated that keratinocytes, which have been long been considered to be a simple physical support for FNEs, can play a sensory role, especially in noxious touch . Therefore, FNEs are not the exclusive transducers of painful information and keratinocytes must closely and specifically communicate with sensory neurons to convey sensory information, which ultimately leads to withdrawal behaviour.…”