Persistent alterations in colonic afferent innervation in a rat model of postinfectious gut dysfunction: Role for changes in peripheral neurotrophic factors

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Abstract

Background

Visceral hypersensitivity in the inflamed gut is related partly to the effects of peripheral neurotrophic factors (NTFs) on local afferent neurons. However, alterations in sensory afferents of distant areas remain unexplored. Using the Trichinella spiralis infection model, which causes a jejunitis, we investigated the remodeling of colonic afferents and the potential role of NTFs.

Methods

Rats were infected with T. spiralis. Inflammatory-like changes, mucosal mast cells (MMCs) dynamics, and expression of nerve growth factor and glial cell line–derived NTFs (glial cell–derived neurotrophic factor, artemin, and neurturin) were determined in the colon up to day 30 postinfection. Functional responses of colonic afferents were determined assessing changes in the expression of sensory-related markers in thoracolumbar (TL)/lumbosacral (LS) dorsal root ganglias (DRGs) following intracolonic capsaicin.

Key Results

Trichinella spiralis induced an inflammatory-like response within the colon, partly resolved at day 30 postinfection, except for a persistent MMC infiltrate. While the jejunum of infected animals showed an up-regulation in the expression of NTFs, a transitory down-regulation was observed in the colon. Overall, T. spiralis effects on DRGs gene expression were restricted to a transient down-regulation of TPRV1. Stimulation with intracolonic capsaicin induced a down-regulation of TRPV1 levels in TL and LS DRGs, an effect enhanced in LS DRGs of infected animals, regardless the postinfection time considered.

Conclusions & Inferences

During intestinal inflammation, spread morphological and functional alterations, including remodeling of visceral afferents, are observed outside the primary region affected by the insult. Similar mechanisms might be operating in states of widespread alterations of visceral sensitivity.

We explored the remodeling of colonic afferents and the potential role of NTFs in Trichinella spiralis-infected rats. T. spiralis induced a colonic inflammatory-like response accompanied by a transient reduction in neurotrophic factor levels. The expression of transient receptor potential vanilloid subtype 1 (TRPV1) in dorsal root ganglia (DRG) was diminished at acute stages of the infection. Moreover, in infected animals, an enhanced down-regulation of TRPV1 levels in lumbosacral DRGs after stimulation with intracolonic capsaicin was observed.

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