A longitudinal study of sensory biomarkers of progression in patients with diabetic peripheral neuropathy using skin biopsies
| Autor: | Paul Facer, G. Byttebier, Theo Meert, H. Narayanaswamy, Maarten Timmers, V.P. Misra, Praveen Anand |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Hot Temperature Biopsy Population Neural Conduction Sensation TRPV1 TRPV Cation Channels Vibration GAP-43 Protein Diabetic Neuropathies Dermis Physiology (medical) medicine Humans Longitudinal Studies education Evoked Potentials Aged Pain Measurement Skin Neurologic Examination education.field_of_study medicine.diagnostic_test business.industry Peripheral Nervous System Diseases General Medicine Middle Aged medicine.disease Immunohistochemistry Peripheral neuropathy medicine.anatomical_structure Nerve growth factor Neurology Skin biopsy Disease Progression Female Surgery Neurology (clinical) business Polyneuropathy Biomarkers Histamine |
| Zdroj: | Journal of Clinical Neuroscience. 19:1490-1496 |
| ISSN: | 0967-5868 |
| Popis: | We aimed to identify biomarkers in skin punch biopsies that could be used to monitor progression of diabetic peripheral neuropathy (DPN), and, in future studies, to assess the efficacy of agents that may reduce progression. Patients with DPN were studied with clinical assessments, skin biopsies, quantitative sensory testing (QST), histamine-induced skin flare, nerve conduction studies and contact heat-evoked potentials (CHEPS). Skin biopsies were performed on two visits with a 6 month interval (n = 29 patients) to quantify intraepidermal (IENF) and subepidermal (SENF) nerve fibres immunoreactive for: protein gene product 9.5 (PGP9.5), a pan-neuronal marker; transient receptor potential cation channel vanilloid 1 (TRPV1), the heat and capsaicin receptor; and growth associated protein-43 (GAP-43), a marker of regenerating fibres. The IENF were counted along the length of four non-consecutive sections, and results were expressed as fibres per millimetre length of section. SENF were measured by image analysis, and the area of highlighted immunoreactivity was obtained as a percentage (% area) of the field scanned. QST, skin flare and CHEPS were also performed at the two visits. We found that IENF and SENF were significantly reduced for both PGP9.5 and TRPV1 between the first and second skin biopsy over 6 months. The annual rate ± standard error of the mean of IENF loss was 3.76 ± 1.46 fibres/mm for PGP9.5, and 3.13 ± 0.58 fibres/mm for TRPV1. The other tests did not show significant changes. Strongly positive GAP-43 nerve fibres were found in deep dermis in the patients with diabetes, even in those with an absence of IENF. We conclude that PGP9.5 and TRPV1 IENF and SENF in skin biopsies are useful markers of progression in DPN, whereas GAP-43 SENF could potentially help detect nerve regeneration in severe neuropathy. |
| Databáze: | OpenAIRE |
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