Avaliação morfológica e funcional do sistema sensorial nociceptivo na prole de ratas com diabetes mellitus

Abstract

Glycemic control during gestational period may be challenging for both diabetic and non-diabetic patients, who may develop gestational diabetes. A series of studies has been indicating that infants of diabetic mothers have also chronic changes that predispose them to diseases throughout life. Although there is no description of alterations in the development of peripheral sensory system, a study in rats by Germani et al. (1999) showed that the levels of mRNA for the neurotrophic factors NGF and BDNF are greatly reduced in the offspring of rats in which diabetes. Since these growth factors are essentials for the development of nociceptive neurons, the present study aims to evaluate if the exposure of rats in utero to maternal diabetes induced by alloxan alters the development of nociceptive peripheral system. The evaluation in newborn animals was done on primary cultures of dorsal root ganglia. Histological evaluation of primary sensory neurons in adult animals was performed using frozen sections of the dorsal root ganglia (L5). To assess the types of sensory fibers it was performed a morphometric analysis in order to categorize neurons according to soma diameters. Neurons were separated in small (<30 microns), medium (between 30 and 40 mm) and large soma (> 40 mm). There was no difference in the distribution of neurons by size in newborns or adults. The subtypes of neurons were also categorized according to the fluorescent labeling: TRPV1 (vanilloid receptor present only on nociceptors), NFH (H neurofilament present in large diameter fibers), substance P (present in peptidergic nociceptive neurons) and IB4 (non peptidergic nociceptive neurons). In the cultures of newborn rats, no difference was observed between the proportions of neurons that were marked positive for the selected molecules. Adult offspring of diabetic rats had a lower proportion of large neurons positive for NFH (P = 0.0078) and a higher proportion of positive neurons for substance P and isolectin B4 (P = 0.0291 and P = 0.0353, respectively). We also performed behavioral tests that showed a lower mechanical sensitivity (electronic Von Frey) of animals in offspring of diabetic mothers after 6 hours of intrapantar carrageenan injection. The offspring of diabetic rats showed an enhanced thermal sensitivity. In the formalin test, it was observed an increased response in the beginning of the second phase, which corresponds to the inflammatory phase of this test. Therefore, in this study it was found that nociceptive responses are altered in adult offspring of diabetic rats and these changes are accompanied by changes in the profile of neurons present in the dorsal root ganglion.