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.


CONCLUSIONS
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.
Kamiya
Hideki
H
Department of Pathology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
Murakawa
Yuichi
Y
Zhang
Weixian
W
Sima
Anders A F
AA
D000818:Animals; D015153:Blotting, Western; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003929:Diabetic Neuropathies / Q000473:pathology* / Q000503:physiopathology*; D005727:Ganglia, Spinal / Q000737:chemistry; D006930:Hyperalgesia; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000648:ultrastructure; D020932:Nerve Growth Factor / Q000032:analysis; D009431:Neural Conduction; D009479:Neuropeptides / Q000032:analysis; D020933:Neurotrophin 3 / Q000032:analysis; D051381:Rats; D011913:Rats, Inbred BB; D017475:Receptors, Nerve Growth Factor / Q000032:analysis; D012583:Schwann Cells / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000737:chemistry; D013997:Time Factors
D009479:Neuropeptides; D020933:Neurotrophin 3; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor