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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
Author(s) -
GarciaPerez E.,
Schönberger T.,
Sumalla M.,
Stierstorfer B.,
Solà R.,
Doods H.,
Serra J.,
Gorodetskaya N.
Publication year - 2018
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.1235
Subject(s) - medicine , microneurography , endocrinology , diabetes mellitus , electrophysiology , diabetic neuropathy , nociceptor , peripheral neuropathy , sensory nerve , dorsal root ganglion , nerve conduction velocity , nociception , sensory system , anatomy , dorsum , receptor , neuroscience , baroreflex , heart rate , blood pressure , biology
Background Peripheral neuropathy is a common complication in type 2 diabetes mellitus (T2 DM ). 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 T2 DM 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.