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

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 . Copyright © 2005 John Wiley & Sons, Ltd.