Neonatal Maternal Deprivation Followed by Adult Stress Enhances Adrenergic Signaling to Advance Visceral Hypersensitivity

【Author】

Wan-Jie Du;Shufen Hu;Xin Li;Ping-An Zhang;Xinghong Jiang;Shan-Ping Yu;Guang-Yin Xu;Laboratory for Translational Pain Medicine, Institute of Neuroscience, Soochow University;Center for Translational Medicine, The Zhangjiagang Affiliated Hospital of Soochow University;Department of Anesthesiology, Emory University School of Medicine;

【Institution】

Laboratory for Translational Pain Medicine, Institute of Neuroscience, Soochow University;Center for Translational Medicine, The Zhangjiagang Affiliated Hospital of Soochow University;Department of Anesthesiology, Emory University School of Medicine;

【Abstract】

The pathophysiology of visceral pain in patients with irritable bowel syndrome remains largely unknown.Our previous study showed that neonatal maternal deprivation(NMD) does not induce visceral hypersensitivity at the age of 6 weeks in rats. The aim of this study was to determine whether NMD followed by adult stress at the age of 6 weeks induces visceral pain in rats and to investigate the roles of adrenergic signaling in visceral pain. Here we showed that NMD rats exhibited visceral hypersensitivity 6 h and 24 h after the termination of adult multiple stressors(AMSs). The plasma level of norepinephrine was significantly increased in NMD rats after AMSs. Whole-cell patch-clamp recording showed that the excitability of dorsal root ganglion(DRG) neurons from NMD rats with AMSs was remarkably increased. The expression of β_2 adrenergic receptors at the protein and mRNA levels was markedly higher in NMD rats with AMSs than in rats with NMD alone. Inhibition of β_2 adrenergic receptors with propranolol or butoxamine enhanced the colorectal distention threshold and application of butoxamine also reversed the enhanced hypersensitivity of DRG neurons. Overall,our data demonstrate that AMS induces visceral hypersensitivity in NMD rats, in part due to enhanced NE-β_2 adrenergic signaling in DRGs.

【Keywords】

Irritable bowel syndrome;;Dorsal root ganglion;;Norepinephrine;;Visceral pain;;Stress

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