Selection of agents modulating gastrointestinal pain
Inventors
Conolly, Eamonn • Kunze, Wolfgang • Bienenstock, John
Assignees
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Publication Number
US-11371985-B2
Publication Date
2022-06-28
Expiration Date
Abstract
The present embodiments relate to selection of agents effective in reducing or preventing gastrointestinal pain in a subject. Such an agent is selected and identified if it is capable of reducing spontaneous and/or induced transient receptor potential vanilloid 1 (TRPV1) activation.
Core Innovation
The invention relates to a selection method for agents, preferably lactic acid bacteria/probiotics, that reduce spontaneous and/or induced transient receptor potential vanilloid 1 (TRPV1) activation. The problem addressed is gastrointestinal pain associated with increased spontaneous and/or induced TRPV1 activation, and the need to prevent and/or reduce such pain by reducing TRPV1 activation locally within the gastrointestinal system of a subject.
The invention further provides a local TRPV1-modulation approach in which TRPV1 activation is assessed using TRPV1-expressing cells and/or ex vivo/nerve-based readouts. TRPV1 modulation is linked to regional and nerve-pathway specificity, including selective action in mesenteric afferent nerve bundles and/or in dorsal root ganglion (DRG) neurons in the gastrointestinal system.
The disclosed example involves a live probiotic Lactobacillus reuteri bacterial strain, for example L. reuteri DSM 17938, having the ability to reduce spontaneous and/or induced TRPV1 activation locally. Supporting findings include reduced mesenteric nerve spontaneous firing, reduced capsaicin/TRPV1 responses with partial insurmountable antagonism, reduced capsaicin-induced DRG Ca2+ influx, and moderation of gastric-distension–evoked bradycardia after oral feeding, with activity suggested to involve conditioned medium.
Claims Coverage
The patent portion provided includes one independent claim describing a method, with additional dependent refinements in claims clm-00002 through clm-00004. The independent claim contains inventive features centered on local treatment of gastrointestinal pain by peroral administration of a live Lactobacillus reuteri strain that selectively reduces TRPV1 activation in defined gastrointestinal neural structures.
Local treatment of gastrointestinal pain by peroral live probiotic targeting TRPV1
A method treating spontaneous and/or induced TRPV1 activation locally within the gastrointestinal system of a subject having gastrointestinal pain associated with increased spontaneous and/or induced TRPV1 activation by administering perorally a live probiotic Lactobacillus reuteri bacterial strain able to reduce spontaneous and/or induced TRPV1 activation locally in the gastrointestinal system.
Selective TRPV1 reduction in mesenteric afferent nerve bundles and/or DRG neurons
The reduction in spontaneous and/or induced TRPV1 activation by the live probiotic Lactobacillus reuteri bacterial strain occurs selectively in mesenteric afferent nerve bundles and/or in dorsal root ganglion (DRG) neurons in the gastrointestinal system.
Overall, the independent claim covers local gastrointestinal treatment of TRPV1-associated pain using a perorally administered live Lactobacillus reuteri strain that selectively reduces spontaneous and/or induced TRPV1 activation in mesenteric afferent nerve bundles and/or DRG neurons.
Stated Advantages
Reduces spontaneous and/or induced TRPV1 activation locally within the gastrointestinal system.
Prevents and/or reduces gastrointestinal pain associated with increased spontaneous and/or induced TRPV1 activation.
Shows regional/nerve-pathway specificity of TRPV1 modulation in mesenteric afferent nerve bundles and/or DRG neurons.
Documented Applications
Treatment of gastrointestinal pain associated with increased spontaneous and/or induced TRPV1 activation, including indications such as IBS, constipation, and infantile colic.
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