Differential impact of keratinocytes and fibroblasts on nociceptor degeneration and sensitization in small fiber neuropathy.
Journal
Pain
ISSN: 1872-6623
Titre abrégé: Pain
Pays: United States
ID NLM: 7508686
Informations de publication
Date de publication:
01 04 2021
01 04 2021
Historique:
received:
26
06
2020
accepted:
20
10
2020
pubmed:
17
11
2020
medline:
20
5
2021
entrez:
16
11
2020
Statut:
ppublish
Résumé
Peripheral denervation and pain are hallmarks of small fiber neuropathy (SFN). We investigated the contribution of skin cells on nociceptor degeneration and sensitization. We recruited 56 patients with SFN and 31 healthy controls and collected skin punch biopsies for immunohistochemical and immunocytochemical analysis of netrin-1 (NTN1) and proinflammatory and anti-inflammatory cytokine expression patterns. We further applied coculture systems with murine dorsal root ganglion (DRG) neurons for skin cell-nerve interaction studies and patch-clamp analysis. Human keratinocytes attract murine DRG neuron neurites, and the gene expression of the axon guidance cue NTN1 is higher in keratinocytes of patients with SFN than in controls. NTN1 slows and reduces murine sensory neurite outgrowth in vitro, but does not alter keratinocyte cytokine expression. In the naive state, keratinocytes of patients with SFN show a higher expression of transforming growth factor-β1 (P < 0.05), while fibroblasts display higher expression of the algesic cytokines interleukin (IL)-6 (P < 0.01) and IL-8 (P < 0.05). IL-6 incubation of murine DRG neurons leads to an increase in action potential firing rates compared with baseline (P < 0.01). Our data provide evidence for a differential effect of keratinocytes and fibroblasts on nociceptor degeneration and sensitization in SFN compared with healthy controls and further supports the concept of cutaneous nociception.
Identifiants
pubmed: 33196576
pii: 00006396-202104000-00027
doi: 10.1097/j.pain.0000000000002122
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1262-1272Informations de copyright
Copyright © 2020 International Association for the Study of Pain.
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