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

Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society
Yu FuX Z Shi

Abstract

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. 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. 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 Kv 1.4 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...Continue Reading

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Citations

Apr 25, 2019·Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland·H NozawaS Ishihara
Nov 5, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Arjun SinghSatish Rattan
Jun 26, 2018·Frontiers in Integrative Neuroscience·Xuan-Zheng ShiShrilakshmi Hegde
Sep 28, 2018·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Sumei Liu
Feb 2, 2021·Frontiers in Psychiatry·Thomas Jan KonturekMiriam Goebel-Stengel
Apr 29, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·You-Min LinXuan-Zheng Shi
Jun 3, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Arjun Singh, Satish Rattan

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