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

Neurosci Bull. 2019 Feb;35(1):4-14. doi: 10.1007/s12264-018-0318-3. Epub 2018 Dec 17.


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 β2 adrenergic receptors at the protein and mRNA levels was markedly higher in NMD rats with AMSs than in rats with NMD alone. Inhibition of β2 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-β2 adrenergic signaling in DRGs.

Keywords: Dorsal root ganglion; Irritable bowel syndrome; Norepinephrine; Stress; Visceral pain.

MeSH terms

  • Adrenergic Agents / pharmacology*
  • Animals
  • Ganglia, Spinal / drug effects
  • Hyperalgesia / drug therapy
  • Hyperalgesia / physiopathology*
  • Hypersensitivity / drug therapy
  • Male
  • Maternal Deprivation*
  • Neurons / drug effects
  • Patch-Clamp Techniques / methods
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Stress, Physiological / physiology*
  • Visceral Pain / chemically induced
  • Visceral Pain / metabolism*


  • Adrenergic Agents