Unmyelinated fiber sensory neuropathy differs in type 1 and type 2 diabetes

Diabetes Metab Res Rev. Sep-Oct 2005;21(5):448-58. doi: 10.1002/dmrr.541.


Background: Neuropathic pain is common in diabetic patients. Degeneration of sensory C-fibers in peripheral nerve plays a prominent role in the generation of neuropathic pain. We examined degenerative changes of C-fibers in two rat models with type 1 and type 2 diabetes.

Methods: Type 1 insulinopenic BB/Wor and type 2 hyperinsulinemic diabetic BBZDR/Wor-rats of 8 months duration with equal exposure to hyperglycemia were examined. Thermal hyperalgesia was monitored using an infrared thermal probe. C-fiber size, number, frequencies of denervated Schwann cells, regenerating C-fibers, type 2 axon/Schwann cell relationship and collagen pockets in the sural nerve were examined morphometrically. Neurotrophic receptor expression was examined by Western blotting. Neurotrophins and neuropeptides were examined by ELISA.

Results: Type 1 rats showed increased thermal hyperalgesia followed by a decrease. Hyperalgesia in type 2 rats showed a slower progression. These findings were associated with a 50% (p < 0.001) loss of C-fibers, increased frequencies of denervated Schwann cells (p < 0.001), regenerating fibers (p < 0.001), collagen pockets (p < 0.001) and type 2 axon/Schwann cell relationship (p < 0.001) in type 1, but not in type 2 rats. Expression of insulin receptor, IGF-1R, TrkA and C was decreased in BB/Wor rats, whereas BBZDR/Wor rats showed milder or no deficits. NGF and NT-3 in sciatic nerve and substance P and calcitonin gene-related peptide in dorsal root ganglia were decreased in type 1, but not in type 2 rats.

Conclusion: The more severe molecular, functional and morphometric abnormalities of nociceptive C-fibers in type 1 insulinopenic rats compared to type 2 hyperinsulinemic rats suggest that impaired insulin action may play a more important pathogenetic role than hyperglycemia per se.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Neuropathies / pathology*
  • Diabetic Neuropathies / physiopathology*
  • Ganglia, Spinal / chemistry
  • Hyperalgesia
  • Male
  • Nerve Fibers, Unmyelinated* / ultrastructure
  • Nerve Growth Factor / analysis
  • Neural Conduction
  • Neuropeptides / analysis
  • Neurotrophin 3 / analysis
  • Rats
  • Rats, Inbred BB
  • Receptors, Nerve Growth Factor / analysis
  • Schwann Cells / ultrastructure
  • Sciatic Nerve / chemistry
  • Time Factors


  • Neuropeptides
  • Neurotrophin 3
  • Receptors, Nerve Growth Factor
  • Nerve Growth Factor