PMID- 29676840
OWN - NLM
STAT- MEDLINE
DCOM- 20190318
LR  - 20190318
IS  - 1532-2149 (Electronic)
IS  - 1090-3801 (Linking)
VI  - 22
IP  - 8
DP  - 2018 Sep
TI  - 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.
PG  - 1457-1472
LID - 10.1002/ejp.1235 [doi]
AB  - 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.
CI  - (c) 2018 European Pain Federation - EFIC(R).
FAU - Garcia-Perez, E
AU  - Garcia-Perez E
AD  - Neuroscience Technologies, Barcelona, Spain.
FAU - Schonberger, T
AU  - Schonberger T
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
FAU - Sumalla, M
AU  - Sumalla M
AD  - Neuroscience Technologies, Barcelona, Spain.
FAU - Stierstorfer, B
AU  - Stierstorfer B
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
FAU - Sola, R
AU  - Sola R
AD  - Neuroscience Technologies, Barcelona, Spain.
FAU - Doods, H
AU  - Doods H
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
FAU - Serra, J
AU  - Serra J
AD  - Neuroscience Technologies, Barcelona, Spain.
FAU - Gorodetskaya, N
AU  - Gorodetskaya N
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180517
PL  - England
TA  - Eur J Pain
JT  - European journal of pain (London, England)
JID - 9801774
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*physiology
MH  - Diabetes Mellitus, Type 2/*complications/physiopathology/psychology
MH  - Diabetic Neuropathies/*etiology/pathology/physiopathology
MH  - Disease Models, Animal
MH  - Male
MH  - Nerve Fibers/*pathology/*physiology
MH  - Pain/etiology/physiopathology/*psychology
MH  - Rats
MH  - Rats, Wistar
MH  - Rats, Zucker
EDAT- 2018/04/21 06:00
MHDA- 2019/03/19 06:00
CRDT- 2018/04/21 06:00
PHST- 2018/04/11 00:00 [accepted]
PHST- 2018/04/21 06:00 [pubmed]
PHST- 2019/03/19 06:00 [medline]
PHST- 2018/04/21 06:00 [entrez]
AID - 10.1002/ejp.1235 [doi]
PST - ppublish
SO  - Eur J Pain. 2018 Sep;22(8):1457-1472. doi: 10.1002/ejp.1235. Epub 2018 May 17.