Vascular and nerve biomarkers in thigh skin biopsies differentiate painful from painless diabetic peripheral neuropathy

Autor: Gordon Sloan, Philippe Donatien, Rosario Privitera, Pallai Shillo, Sharon Caunt, Dinesh Selvarajah, Praveen Anand, Solomon Tesfaye
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Frontiers in Pain Research, Vol 5 (2024)
Druh dokumentu: article
ISSN: 2673-561X
DOI: 10.3389/fpain.2024.1485420
Popis: BackgroundIdentifying distinct mechanisms and biomarkers for painful diabetic peripheral neuropathy (DPN) is required for advancing the treatment of this major global unmet clinical need. We previously provided evidence in calf skin biopsies that disproportion between reduced sensory small nerve fibers and increased blood vessels may distinguish painful from non-painful DPN. We proposed that overexposure of the reduced nerve fibers in DPN to increased hypoxemia-induced vasculature and related algogenic factors, e.g., nerve growth factor (NGF), leads to neuropathic pain. To further investigate this proposed mechanism, we have now studied more proximal thigh skin biopsies, to see if the same disproportion between increased vasculature and decreased nerve fibers generally differentiates painful DPN from painless DPN.MethodsA total of 28 subjects with type 2 diabetes (T2DM) and 13 healthy volunteers (HV) underwent detailed clinical and neurophysiological assessments, based on the neuropathy composite score of the lower limbs [NIS(LL)] plus 7 tests. T2DM subjects were subsequently divided into three groups: painful DPN (n = 15), painless DPN (n = 7), and no DPN (n = 6). All subjects underwent skin punch biopsy from the upper lateral thigh 20 cm below the anterior iliac spine.ResultsSkin biopsies showed decreased PGP 9.5-positive intraepidermal nerve fiber (IENF) density in both painful DPN (p
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