Document Type

Journal Article

Department/Unit

School of Chinese Medicine

Title

Nerve growth factor-mediated neuronal plasticity in spinal cord contributes to neonatal maternal separation-induced visceral hypersensitivity in rats

Language

English

Abstract

Visceral hyperalgesia is a multifactorial gastrointestinal disorder which featured with alterations of abdominal motility and/or gut sensitivity, and is believed to be triggered by environmental stressor or psychological factors. However, its etiology remains incompletely understood. In this study, we aimed to investigate whether nerve growth factor (NGF)-mediated neuronal plasticity is involved in neonatal maternal separation (NMS)-induced visceral hypersensitivity in adult rats, and whether NGF antagonist can attenuate or block such development. In our experiments, animals subjected to NMS were developed with visceral hyperalgesia at age of 8 weeks. The threshold for visceral pain among these NMS rats was remarkably lowered than that of the normal handling (NH) rats; however, the expression levels of NGF, c-fos, calcitonin gene-related peptide (CGRP), Substance P, and tyrosine kinases A (TrkA) were notably elevated in lumbosacral spinal cord and/or dorsal root ganglion (DRG) when comparing to those of the NH rats. Further, as intra-peritoneal administration of NGF (10 μl at 1 μg/kg/day) was given to NH rats during neonatal period, effects that comparable to NMS induction were observed in the adulthood. In contrast, when NMS rats were treated with NGF antagonist K252a (10 μl/day from postnatal days 2-14), which acts against tyrosine kinases, the neonatal stress-induced down-shifted visceral pain threshold was restored and neuronal activation, specifically NGF and neuropeptide production, was attenuated. In conclusion, our data strongly suggest that NGF triggers neuronal plasticity and plays a crucial role in NMS-induced visceral hypersensitivity in which NGF antagonism provides positive inhibition via blocking the tyrosine phosphorylation of TrkA. © 2011 European Federation of International Association for the Study of Pain Chapters.

Keywords

Neonatal maternal separation (NMS), Nerve growth factor (NGF), Neuronal plasticity, Visceral hypersensitivity

Publication Date

2012

Source Publication Title

European Journal of Pain

Volume

16

Issue

4

Start Page

463

End Page

472

Publisher

Wiley

DOI

10.1016/j.ejpain.2011.07.005

ISSN (print)

10903801

ISSN (electronic)

15322149

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