NGF mediated long-lasting changes in central nervous system in neonatal maternal separation induced-visceral hyperalgesia

Psychological stress plays an important role in the aetiology of visceral hyperalgesia. The stress-induced visceral hyperalgesia was shown to involve alternations in central neuronal plasticity and activity in responding to visceral nociceptive stimuli. Nerve growth factor (NGF) is essential for the development and maintenance of sensory neurons, and the formation of central neuronal plasticity for visceral perception. The present study aimed to investigate whether neonatal maternal separation (NMS) cause changes in neuronal plasticity and the relationship of these changes in plasticity with the expression of NGF and TrkA in the lumbarsacral spinal cord in adult rats. Male Wistar rat pups were subjected to 180 min daily NMS for 13 consecutive days. The expression of NGF and TrkA was examined in NH and NMS rats with (+) or without (-) colorectal distention (CRD) as determined by western blot analysis and immunohistochemistry. In the present results, the threshold that elicited AWR was significantly lower in NMS than NH rats. Results of western blot analysis indicated NMS and CRD significant up-regulated NGF protein level in the lumbarsacral spinal cord of rats. Assessments of optical densities revealed an increase in TrkA-ir fibers density in laminae I-III and laminae V-VI of NMS+CRD compared to NH+CRD rats. Double immunofluorescence revealed no significant difference in term of the intensity of TrkA-ir in CGRP positive fibers was found among groups. Quantitative analysis of TrkA-ir neurons indicated a significant increase in mean number of TrkA-ir neurons in laminae V-VI of NMS+CRD compared to NH+CRD rats. Double immunofluorescence of TrkA and Fos showed that CRD induced TrkA expression in Fos-positive neurons in laminae V-VI and lamina X of rats, but no significant was found in between NMS+CRD and NH+CRD. These indicate that NGF is a crucial mediator for the changes in neuronal plasticity that occur in NMS-induced visceral hyperalgesia