Sensory neurons are an important component of the skin because their nerve endings innervate its different layers, including the epidermis. Their role in detecting environmental variations (temperature, pressure, cosmetic products, pollution, etc.) is essential and well known, but sensory neurons can also detect internal biological phenomena. Following their stimulation, sensory neurons released neuropeptides that will activate in turn skin cells creating a crosstalk between the sensory neurons and skin cells.

Dysregulations can occur and impact the functioning of sensory neurons. This is the case in the phenomenon of sensitive skin leading to the appearance of unpleasant sensations and the establishment of an inflammatory state due for part to the activation of signaling pathways such as TRPV1 signaling pathways. Targeting these pathway is essential to cut off the vicious circle of sensitive skin and irritation and bring a soothing sensation.

Neuron Experts has developed in vitro models using human mature sensory neurons from human induced pluripotent cells (hiPS) technology and human keratinocytes to assess the impact of ingredients on TRPV1 signaling pathways. In these models, capsaicin, an irritant compound, is used to activate TRPV1 receptors on sensory neurons, leading to the release of the neuropeptide CGRP which can be quantified by ELISA. This neuropeptide is responsible for unpleasant sensations and plays an important role in activating the release of pro-inflammatory cytokines in the skin.

The impact of soluble ingredients on the TRPV1 signaling pathway can be evaluated in a 2 dimension co-culture system of human sensory neurons and normal human epidermal keratinocytes.

Figure 1: Measurement of neuropeptide CGRP release in a co-culture of human sensory neurons and normal human epidermal keratinocytes. Capsaicin was used to activate CGRP release by activating TRPV1 receptors of sensory neurons. Data are expressed in percentage of the measured amount of CGRP in the negative control.

Capsazepine, a selective inhibitor of TRPV1 receptors, and β-endorphin, a non-specific inhibitor of sensory neurons activity were incubated in presence of the co-culture system and demonstrated their ability to inhibit CGRP release in the 2D co-culture.

In collaboration with StratiCELL, Neuron Experts has developed a 3 dimension co-culture system of reconstructed epidermises and sensory neurons allowing to test finish products or insoluble ingredients. The molecule capsazepine was included in a formulation and applied topically on reconstructed epidermises while capsaicin was incubated in the culture medium to recreate an irritating environment for neurons.

Figure 2: Measurement of neuropeptide CGRP release in a 3 dimension co-culture model  of human sensory neurons and reconstructed epidermises. Capsaicin was used to activate CGRP release by activating TRPV1 receptors of sensory neurons.

Capsazepine, in the 3D model, confirms its ability to inhibit the release of CGRP due to the activation of TRPV1 receptors on sensory neurons, demonstrate the usefulness of this model for evaluating the ability of ingredients or finished products to provide a soothing sensation on sensitive skin.

You can contact Neuron Experts to discover the full range of in vitro solutions available to explore the impact of ingredients on sensory neurons and skin cells crosstalk.

Visit the Neuron Experts website here : https://www.neuronexperts.com/.

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CONTACT

Elodie Gras Lavigne – Head of Neurodermatology department

elodie.gras@neuronexperts.com and contact@neuronexperts.com