title: Increased cutaneous NGF and CGRP-labelled trkA-positive intra-epidermal nerve fibres in rat diabetic skin.
abstract: In this study we have determined the amount of Nerve Growth Factor (NGF) and the innervation density of the glabrous hindpaw skin of diabetic rats (n=4) and controls (n=3). The proportion of intra-epidermal nerve fibres (IENF) expressing the high affinity NGF receptor (trkA) and calcitonin gene-related peptide (CGRP) were also determined. Four weeks after induction of diabetes by intraperitoneal streptozotocin injection skin was analyzed for: (i) NGF content using ELISA and (ii) the innervation density of peptidergic afferents that also expressed trkA using immunocytochemistry. NGF levels were approximately three-fold higher in diabetic skin compared to controls (diabetic: 134.7±24.0 (SD) pgml(-1), control: 42.7±21.5pgml(-1), p=0.002). As expected there was a significant reduction in IENF density in diabetic skin (2.7±1.3 fibresmm(-1)) compared to controls (6.9±1.5 fibresmm(-1); p=0.01). In diabetic rats there was no significant difference in the proportion of trkA-labelled IENF (diabetic 74±21%; control 83±15%, p=0.6), but significantly more trkA-positive IENF were also labelled by CGRP antibodies in diabetic skin compared to controls (diabetic 89±22%; control 38±2%, p=0.03). These data suggest that in diabetes the upregulation of cutaneous NGF may 'over-troph' the surviving axons, increasing CGRP labelling, which may be important in the aetiology of painful diabetic neuropathy.
authors: The Unit of Oral and Maxillofacial Medicine and Surgery, School of Clinical Dentistry, The University of Sheffield, Claremont Crescent, Sheffield S10 2TA, United Kingdom.
authors: Laura
authors: L
authors: Evans
authors: David
authors: D
authors: Andrew
authors: Peter
authors: P
authors: Robinson
authors: Fiona
authors: F
authors: Boissonade
authors: Alison
authors: A
authors: Loescher
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D008297:Male; D009412:Nerve Fibers / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism*; D012867:Skin / Q000294:innervation / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: D020932:Nerve Growth Factor; D020917:Receptor, trkA; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide