Characterisation of the pathophysiology of neuropathy and sensory dysfunction in a mouse model of recessive dystrophic epidermolysis bullosa

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dc.catalogadoraba
dc.contributor.authorSchmidt, Daniela
dc.contributor.authorDíaz Céspedes, Paula Estefany
dc.contributor.authorMuñoz, Daniela
dc.contributor.authorEspinoza Mihovilovic, Fernanda Mileva
dc.contributor.authorNystrom, Alexander
dc.contributor.authorFuentes, Ignacia
dc.contributor.authorEzquer, Marcelo
dc.contributor.authorBennett, David L.
dc.contributor.authorCalvo Bascuñán, Margarita
dc.date.accessioned2023-08-28T15:11:47Z
dc.date.available2023-08-28T15:11:47Z
dc.date.issued2022
dc.description.abstractRecessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic condition in which mutations in the type VII collagen gene (COL7A1) lead to decreased expression of this anchoring protein of the skin, causing the loss of stability at the dermo-epidermal junction. Most patients with RDEB experience neuropathic pain and itch due to the development of a small fibre neuropathy, characterised by decreased intraepidermal innervation and thermal hypoaesthesia. To understand the physiopathology of this neuropathy, we used a mouse model of RDEB (Col7a1(flNeo/flNeo)) and performed a detailed characterisation of the somatosensory system. Col7a1(flNeo/flNeo) mice showed a decrease in heat sensitivity, an increase in spontaneous scratching, and a significant decrease in intraepidermal nerve fibre density in the hindpaw; these changes were distal because there was no significant loss of unmyelinated or myelinated fibres in the nerve trunk. Of interest, we observed a decrease in axon diameter in both myelinated and unmyelinated fibres. This axonal damage was not associated with inflammation of the dorsal root ganglion or central projection targets at the time of assessment. These results suggest that in RDEB, there is a distal degeneration of axons produced by exclusive damage of small fibres in the epidermis, and in contrast with traumatic and acute neuropathies, it does not induce sustained neuroinflammation. Thus, this animal model emphasizes the importance of a healthy cutaneous environment for maintenance of epidermal innervation and faithfully replicates the pathology in humans, offering the opportunity to use this model in the development of treatments for pain for patients with RDEB.
dc.fechaingreso.objetodigital2023-08-28
dc.fuente.origenWOS
dc.identifier.doi10.1097/j.pain.0000000000002599
dc.identifier.eissn1872-6623
dc.identifier.issn0304-3959
dc.identifier.urihttp://doi.org/10.1097/j.pain.0000000000002599
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/74513
dc.identifier.wosidWOS:000854379700021
dc.information.autorucFacultad de Ciencias Biológicas; Díaz Céspedes, Paula Estefany; 0000-0002-2779-9081; 1070756
dc.information.autorucFacultad de Ciencias Biológicas; Espinoza Mihovilovic, Fernanda Mileva; 0000-0003-1391-5480; 1015221
dc.information.autorucFacultad de Ciencias Biológicas; Calvo Bascunan Margarita; 0000-0003-3349-9189; 3457
dc.issue.numero10
dc.language.isoen
dc.nota.accesoContenido completo
dc.pagina.final2060
dc.pagina.inicio2052
dc.publisherLIPPINCOTT WILLIAMS & WILKINS
dc.revistaPAIN
dc.rightsacceso abierto
dc.subjectRDEB
dc.subjectMouse model
dc.subjectNeuropathy
dc.subjectNeuropathic pain
dc.subjectSmall-fibre neuropathy
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleCharacterisation of the pathophysiology of neuropathy and sensory dysfunction in a mouse model of recessive dystrophic epidermolysis bullosa
dc.typeartículo
dc.volumen163
sipa.codpersvinculados1070756
sipa.codpersvinculados1015221
sipa.codpersvinculados3457
sipa.indexWOS
sipa.trazabilidadWOS;2022-10-11
sipa.trazabilidadORCID;2023-08-21
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