Role of brain-derived neurotrophic factor in the pathogenesis of distention-associated abdominal pain in bowel obstruction

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5 Scopus citations

Abstract

Background: Previous studies found that visceral sensitivity is increased in bowel obstruction (BO). We hypothesized that mechanical stress-induced expression of BDNF in smooth muscle cells (SMC) of the distended bowel plays a critical role in visceral hypersensitivity in BO by altering voltage-gated K+ channel (Kv) activity in sensory neurons. Methods: Partial colon obstruction was maintained in rats for 7 days. Colon-projecting neurons in the dorsal root ganglia (DRG, T13 to L2) were isolated for electrophysiological and gene expression studies. Key Results: Compared to controls, membrane excitability of colon-projecting DRG neurons was markedly enhanced in BO. The densities of total Kv and transient A-type (IA) K+ currents, but not sustained delayed IK current, were significantly reduced in the neurons in BO. The mRNA expression of IA subtype Kv1.4 in colon neurons was down-regulated in BO. Expression of BDNF mRNA and protein was dramatically increased in colonic smooth muscle of the distended segment, but not in the non-distended aboral segment. Mechanical stretch of colon SMC in vitro increased BDNF expression. Treatment with anti-BDNF antibody restored total Kv and IA currents of neurons from BO rats. Administration of Trk B inhibitor ANA-12 blocked BO-associated changes of neuronal excitability, Kv activity and gene expression in obstruction. Conclusions and Inferences: Mechanical stress-induced expression of BDNF in colon SMC plays a critical role in visceral hypersensitivity in BO by suppressing A-type K+ currents and gene expression in sensory nerve. These findings help to identify therapeutic targets for distention-associated abdominal pain in the gut.

Original languageEnglish (US)
Article numbere13373
JournalNeurogastroenterology and Motility
Volume30
Issue number10
DOIs
StatePublished - Oct 2018

Keywords

  • abdominal pain
  • mechanical stress
  • neurotrophin
  • smooth muscle cell
  • visceral sensitivity

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

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