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

• DOI: 10.1002/dmrr.541
• Publication Date: 2005-03-03T13:46:35Z
• Authors: Hideki Kamiya; Yuichi Murakawa; Weixian Zhang; Anders A. F. Sima
• Keywords: Male; Nerve Fibers, Unmyelinated; Time Factors; Blotting, Western; Neuropeptides; Neural Conduction; Receptors, Nerve Growth Factor; Sciatic Nerve; Rats; 3. Good health; 03 medical and health sciences; Diabetes Mellitus, Type 1; 0302 clinical medicine; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Neurotrophin 3; Hyperalgesia; Ganglia, Spinal; Nerve Growth Factor; Animals; Rats, Inbred BB; Schwann Cells

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.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.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.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.