Thursday, September 22nd
Dysfunction of Keratinocytes in Small Fiber Neuropathy is in Part the Cause of Lack of Epidermal Reinnervation
Fibers in the epidermis degenerate in pathological conditions, but once the insult is removed, they should grow back and completely reinnervate the epidermis (JCompNeurol 2003). However, this doesn’t occur in chronic SFN. In this presentation I will show data on a particular case of SFN-induced by a skin disease (Recessive Dystrophic Epidermolysis Bullosa or RDEB) where we have seen that neurotrophins that should guide the reinnervating axonal cone, failed to be secreted. We have observed that the skin of healthy volunteers increases their RNA/protein expression of NGF and GDNF at least 4-7 times after a skin scratch injury. However, RDEB patients with a secondary SFN, show no neurotrophins response following injury. In the epidermis the largest amount of neurotrophins comes from keratinocytes. Interestingly, human keratinocytes from healthy subjects, but not from RDEB, increased their in vitro release of neurotrophins following scratch injury. Furthermore, conditioned medium from healthy keratinocytes, but not from RDEB keratinocytes, stimulate sensory neuron axonal growth in vitro. In an animal model of SFN induced by RDEB we have demonstrated that a topical treatment with neurotrophins receptor agonists could revert thermal hypoesthesia and reduced intraepidermal fibres. These findings give hope for a treatment of SFN-induced by skin conditions.