Pattern of distribution of calcitonin gene-related Peptide in the dorsal root ganglion of animal models of diabetes mellitus

Abstract

This article examined the pattern of distribution of calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DRG) of normal and diabetic Wistar, Zucker lean, and Goto-Kakizaki (GK) rats to determine whether there are changes in the number and pattern of distribution of CGRP-positive neurons after the onset of latent or overt diabetes. Type 1 diabetes mellitus was induced in Wistar rats by a single dose of streptozotocin (STZ) given intraperitoneally (60 mg/kg body weight). Four weeks after the induction of diabetes mellitus, diabetic (n = 6) and normal (n = 6), Zucker lean (n = 6), and GK (n = 6) rats were anesthetized with chloral hydrate and their DRGs were removed and processed for immunohistochemistry. CGRP-positive neurons were observed in the DRG of normal and diabetic Wistar, Zucker lean (nondiabetic), and GK (animal model of type 2 diabetes) rats. CGRP was present in small-, medium-, and large-sized neurons of the DRG in these three animal models. Only a small percentage of large-sized neurons contains CGRP. The number of CGRP-positive neurons was significantly (P < 0.05) reduced in STZ-induced diabetic Wistar and GK rats compared to normal Wistar and Zucker lean rats. Moreover, the quantity of CGRP-containing varicose nerves was less in diabetic Wistar and GK rats compared to control Wistar and Zucker lean rats. The reduced number of CGRP-positive neurons in the DRG of GK rats indicated that subjects with latent diabetes may already have dysfunctional CGRP metabolism and thus diabetic neuropathy.