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 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.
Highlights
Irritable bowel syndrome (IBS) is a common gastrointestinal disease characterized by disorders of intestinal motility and accompanied by chronic abdominal pain [1,2,3]
We demonstrated that neonatal maternal deprivation (NMD) rats exhibited reduced thresholds and increased abdominal withdrawal reflex scores to Colorectal Distention (CRD) when compared with age-matched control rats after exposure to multiple stressors as adults
This indicates that a combination of NMD and adult multiple stressors (AMSs) exacerbated the symptoms by enhancing visceral hypersensitivity in NMD rats at the age of 6 weeks
Summary
Irritable bowel syndrome (IBS) is a common gastrointestinal disease characterized by disorders of intestinal motility and accompanied by chronic abdominal pain [1,2,3]. The treatment of chronic abdominal pain is difficult [4]. Research on this disease is progressing slowly due to the lack of suitable animal models. Our previous studies have shown that neonatal maternal deprivation (NMD) can induce chronic visceral pain in adult rats at the age of 7 weeks but not at 6 weeks [9, 10]. It seems that the age of 7 weeks is an important time point for the development of visceral hypersensitivity in rats with NMD. It is unknown whether 6-week-old NMD rats are more sensitive to environmental stimuli than age-matched controls
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