Behavioural, morphological and electrophysiological assessment of the effects of type 2 diabetes mellitus on large and small nerve fibres in Zucker diabetic fatty, Zucker lean and Wistar rats

Background Peripheral neuropathy is a common complication in type 2 diabetes mellitus (T2DM). The most common presentation is in the form of a distal axonal sensory‐motor polyneuropathy that involves large and small nerve fibres in variable proportion. Methods Zucker Diabetic Fatty (ZDF), Zucker Lea...

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Bibliographic Details
Published in:European journal of pain 2018-09, Vol.22 (8), p.1457-1472
Main Authors: Garcia‐Perez, E., Schönberger, T., Sumalla, M., Stierstorfer, B., Solà, R., Doods, H., Serra, J., Gorodetskaya, N.
Format: Article
Language:English
Subjects:
Animals
Behavior, Animal - physiology
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - physiopathology
Diabetes Mellitus, Type 2 - psychology
Diabetic Neuropathies - etiology
Diabetic Neuropathies - pathology
Diabetic Neuropathies - physiopathology
Disease Models, Animal
Male
Nerve Fibers - pathology
Nerve Fibers - physiology
Pain - etiology
Pain - physiopathology
Pain - psychology
Rats
Rats, Wistar
Rats, Zucker
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Summary:Background Peripheral neuropathy is a common complication in type 2 diabetes mellitus (T2DM). The most common presentation is in the form of a distal axonal sensory‐motor polyneuropathy that involves large and small nerve fibres in variable proportion. Methods Zucker Diabetic Fatty (ZDF), Zucker Lean (ZL) and Wistar Han (WH) rats were used to assess the behavioural, morphological and electrophysiological effects that T2DM have on peripheral large and small nerve fibres of 6‐ to 40‐week‐old rats. Results ZDF rats presented mechanical hypersensitivity that initially worsened in parallel to the progression of diabetes and eventually reverted at later stages of the disease. The reversal from hypersensitivity to hyposensitivity paralleled a reduction in the number of intraepithelial skin nerve terminals and in the nerve fibre lengths. However, no increased levels of degeneration of dorsal root ganglion neurons were observed. Nerve conduction studies showed a reduction in sensory and motor nerve conduction velocity (CV) in hyperglycaemic ZDF rats. Microneurography showed significant alterations in several parameters of activity‐dependent slowing (ADS) of mechano‐insensitive C‐nociceptors in ZDF rats. Surprisingly, some of these changes were also observed in ZL rats. Moreover, we found spontaneous activity in all three strains implying that C‐nociceptors become hyperexcitable and spontaneously active not only in ageing hyperglycaemic ZDF rats but also in age‐matched and apparently normoglycaemic ZL and WH rats fed with the same diet. Conclusions ZDF rats presented a diabetic neuropathy involving large and small nerve fibres; additionally, ZL and WH rats also showed early small abnormalities in C‐fibres, clearly detected by microneurography Significance This study provides a functional description of large and small nerve fibre function in a diabetic model that recapitulates many of the findings observed in patients suffering from type 2 diabetes mellitus.
ISSN:1090-3801
1532-2149
DOI:10.1002/ejp.1235