Background & Aims

The skin Small Fiber Neuropathy (SFN) is predominantly due to the loss of sensory innervations and is large proportion of misdiagnosed painful skin conditions. The mechanism of sensory neuropathy in chronic inflammatory skin disease could open up a new dimension in the comprehensive understanding of tissue homeostasis and disease of the skin. Non-immune cells such as keratinocytes and fibroblasts, they designate processes of tissue damage, and cutaneous nerve fibers regeneration. Elongation of the cutaneous nerve fibers is guided by gradients of neurotrophic factors produced mainly by skin cells. The cutaneous reinnervating in the epidermis is guided by a fine balance between nerve elongation and nerve repulsion factors

Methods

We recruited a cohort of epidermolysis bullosa (RDEB) and atopic dermatitis patients, and their matched controls and then perform a small skin injury and collected biopsies from the sites 10 days after injury. We used digital PCR to evaluate changes in mRNA expression of nerve elongation and repulsion factors, and secretory products of skin and inflammatory cells using LUMINEX. We co-cultured primary keratinocytes from patients and controls and sensory neurons to test the direct effect of the elongation and repulsion molecules on axonal regeneration and degeneration

Results

We observed a “growth factor” response following skin injury in control subjects, which was not seen in RDEB. Rat sensory neurons grown with conditioned medium from scratched control human keratinocytes showed increased neurite outgrowth compared to scratched neurons grown with medium from SFN-RDEB.

Conclusions

Patients with SFN secondary to RDEB do not respond secreting growth factors following skin injury as control subjects do. Keratinocytes from healthy donors secrete functionally active NGF and GDNF following in vitro injury, probably to promote regeneration of injured intraepidermal axons. However, keratinocytes from our patients fail to secrete neurotrophic factors. This may be a reason why intraepidermal fibres in these patients do not regenerate following skin injury (produced by their skin condition) and let them to present an SFN.

References

von Bischhoffshausen, S., Ivulic, D., Alvarez, P., Schuffeneger, V. C., Idiaquez, J., Fuentes, C., Morande, P., Fuentes, I., Palisson, F., Bennett, D. L. H., & Calvo, M. (2017). Recessive dystrophic epidermolysis bullosa results in painful small fibre neuropathy. Brain : a journal of neurology, 140(5), 1238–1251.

Schmidt, D., Díaz, P., Muñoz, D., Espinoza, F., Nystrom, A., Fuentes, I., Ezquer, M., Bennett, D. L., & Calvo, M. (2022). Characterisation of the pathophysiology of neuropathy and sensory dysfunction in a mouse model of recessive dystrophic epidermolysis bullosa. Pain, 163(10), 2052–2060.

Presenting Author

Paula Diaz

Poster Authors

Paula Díaz, PhD(c)

PhD (c)

Pontificia Universidad Católica de Chile

Lead Author

Ignacia Fuentes

PhD

Pontificia Universidad Católica de Chile

Lead Author

Margarita Calvo

Pontificia Universidad Católica de Chile

Lead Author

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Neuropathic Pain - Peripheral