title: Changes in epidermal thickness and cutaneous innervation during maturation in long-term diabetes.
abstract: OBJECTIVE
  Peripheral nerve fiber depletion in patients with chronic diabetes mellitus (DM) was linked to neuropathic symptoms, development of pain, foot ulcerations and lower extremity amputation. The aim of this study was to analyze cutaneous changes, including paw epidermal thickness and intraepidermal nerve fiber (IENF) density in long-term diabetes, in rats 6 months and 12 months after induction of diabetes.
  
  
  METHODS
  Epidermal thickness and IENF density were studied in Sprague-Dawley diabetic rats 6 months and 12 months after diabetes induction with streptozotocin. Epidermal thickness was evaluated using hematoxylin and eosin staining. Peripheral nerve fibers were stained with polyclonal antiserum against protein gene product 9.5 (PGP 9.5). Successful diabetes induction was validated by measuring plasma glucose and body mass regularly throughout the experiment.
  
  
  RESULTS
  This study showed that long-term diabetes, induced in Sprague-Dawley rats with streptozotocin, is characterized with significant epidermal thinning and reduction of intraepidermal nerve fibers, 6 months and 12 months after induction of diabetes.
  
  
  CONCLUSIONS
  Long-term studies of streptozotocin models of diabetes could be used for making normative IENF densities that can be later used as age-dependent normative values for studying new treatment modalities.
authors.affiliation: Laboratory for Pain Research, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia.
authors.forename: Antonia
authors.initials: A
authors.lastname: Jelicic Kadic
authors.affiliation: Laboratory for Pain Research, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia.
authors.forename: Matija
authors.initials: M
authors.lastname: Boric
authors.affiliation: Laboratory for Pain Research, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia.
authors.forename: Marin
authors.initials: M
authors.lastname: Vidak
authors.affiliation: Laboratory for Pain Research, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia.
authors.forename: Lejla
authors.initials: L
authors.lastname: Ferhatovic
authors.affiliation: Laboratory for Pain Research, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia. Electronic address: livia@mefst.hr.
authors.forename: Livia
authors.initials: L
authors.lastname: Puljak
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D004817:Epidermis / Q000294:innervation* / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Diabetes mellitus; Maturation; Nerves; Rat; Skin