Work

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

Year: 2018

Type: article

Abstract: Background Previous studies found that visceral sensitivity is increased in bowel obstruction (BO). We hypothesized that mechanical stress‐induced expression ofBDNFin smooth muscle cells (SMC) of the distended bowel plays a critical role in visceral hypersensitivity inBOby 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‐projectingDRGneurons was markedly enhanced inBO. The densities of total Kvand transient A‐type (IA) K+currents, but not sustained delayedIKcurrent, were significantly reduced in the neurons inBO. ThemRNAexpression ofIAsubtype Kv1.4 in colon neurons was down‐regulated inBO. Expression ofBDNF mRNAand protein was dramatically increased in colonic smooth muscle of the distended segment, but not in the non‐distended aboral segment. Mechanical stretch of colonSMCin vitro increasedBDNFexpression. Treatment with anti‐BDNFantibody restored total KvandIAcurrents of neurons fromBOrats. Administration of Trk B inhibitorANA‐12 blockedBO‐associated changes of neuronal excitability, Kvactivity and gene expression in obstruction. Conclusions and Inferences Mechanical stress‐induced expression ofBDNFin colonSMCplays a critical role in visceral hypersensitivity inBOby 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.

Source: Neurogastroenterology & Motility

DOI: 10.1111/nmo.13373

Authors: Y. Fu, Y. M. Lin, J. H. Winston, R. Radhakrishnan, L.‐Y. M. Huang, X. Z. Shi

Institution: The University of Texas Medical Branch at Galveston

Language: English

Topic: Pain Mechanisms and Treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases