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) pg ml −1, control: 42.7 ± 21.5 pg ml −1, p = 0.002). As expected there was a significant reduction in IENF density in diabetic skin (2.7 ± 1.3 fibres mm −1) compared to controls (6.9 ± 1.5 fibres mm −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.
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