Molecular and pathological studies in the posterior interosseous nerve of diabetic and non-diabetic patients with carpal tunnel syndrome

Moaz A. Mojaddidi, Mohammed S. Ahmed, Razwan Ali, Maria Jeziorska, Ahmed Al-Sunni, Niels O B Thomsen, Lars B. Dahlin, Rayaz Malik

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Aims/hypothesis: We sought to establish the molecular and pathological changes predisposing diabetic and non-diabetic patients to the development of carpal tunnel syndrome (CTS). Methods: The posterior interosseous nerve (PIN) was biopsied in 25 diabetic and 19 non-diabetic patients undergoing carpal tunnel decompression for CTS. Detailed morphometric and immunohistological analyses were performed in the nerve biopsy. Results: In diabetic patients median nerve distal motor latency was prolonged (p<0.05 vs non-diabetic patients), PIN myelinated fibre density (p<0.05), fibre area (p<0.0001) and axon area (p<0.0001) were reduced, the percentage of unassociated Schwann cell profiles (p<0.0001) and unmyelinated axon density (p<0.0001) were increased and the axon diameter was reduced (p<0.0001). Endoneurial capillary basement membrane area was increased (p<0.0001) in diabetic patients, but endothelial cell number was increased (p<0.01) and luminal area was reduced (p<0.05) in non-diabetic patients with CTS. There was no difference in the expression of hypoxia-inducible factor 1α between diabetic and non-diabetic patients with CTS. However, the expression of vascular endothelial growth factor A (VEGF) (p<0.05) and its receptors VEGFR-1 (p<0.01) and VEGFR-2 (p<0.05) was significantly increased in diabetic patients, particularly those with type 1 diabetes, and related to the severity of nerve fibre pathology. Conclusions/interpretation: This study demonstrates increased nerve fibre and microvascular pathology in relation to enhanced expression of VEGF and its receptors in a non-compressed nerve in diabetic compared with non-diabetic patients with CTS. It therefore provides a potential molecular and pathological basis for the predisposition of diabetic patients to the development of CTS.

Original languageEnglish
Pages (from-to)1711-1719
Number of pages9
JournalDiabetologia
Volume57
Issue number8
DOIs
Publication statusPublished - 2014

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Keywords

  • Carpal tunnel syndrome
  • Diabetes
  • HIF-1α
  • Microangiopathy
  • Myelinated fibre
  • Neuropathy
  • Unmyelinated fibre
  • VEGF

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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