Selection of Agents Modulating Gastrointestinal Pain
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.
1 - 31 . (canceled)
32 . A method for selecting an agent for reducing gastrointestinal pain in a subject, said method comprising:
selecting an agent that reduces spontaneous and/or induced transient receptor potential vanilloid 1, TRPV1, activation, wherein said agent is a bacterial strain or conditioned medium from the bacterial strain.
33 . The method according to claim 32 , further comprising:
contacting a cell expressing TRPV1 with the bacterial strain or conditioned medium from the bacterial strain;
measuring spontaneous and/or induced TRPV1 activation in said cell following the contacting; and
selecting said bacterial strain or conditioned medium from the bacterial strain as an agent effective in reducing gastrointestinal pain when said measured spontaneous and/or induced TPRV1 activation is lower than control TPRV1 activation.
34 . The method according to claim 33 , wherein measuring said spontaneous and/or induced TRPV1 activation comprises measuring Ca2+ influx in said cell induced by capsaicin, pH change and/or heat.
35 . The method according to claim 33 , wherein measuring said spontaneous and/or induced TRPV1 activation comprises measuring temperature-gated ion-channel activity in said cell.
36 . The method according to claim 32 , further comprising:
contacting an ex vivo gastrointestinal segment with attached mesenteric tissue with the bacterial strain or conditioned medium from the bacterial strain;
measuring spontaneous and/or induced mesenteric afferent firing in said ex vivo gastrointestinal segment following the contacting; and
selecting said bacterial strain or conditioned medium from the bacterial strain as an agent effective in reducing gastrointestinal pain when said measured spontaneous and/or induced mesenteric afferent firing is lower than control mesenteric afferent firing.
37 . The method according to claim 32 , wherein the bacterial strain is a lactic acid bacterial strain and the conditioned medium is a conditioned medium from a lactic acid bacterial strain.
38 . The method according to claim 37 , wherein the lactic acid bacterial strain is a Lactobacillus reuteri strain and the conditioned medium is a conditioned medium from a Lactobacillus reuteri strain.
39 . The method according to claim 32 , wherein selecting said bacterial strain or conditioned medium from the bacterial strain comprises selecting a bacterial strain or conditioned medium from the bacterial strain that reduces spontaneous and/or induced TRPV1 activation and modulates gastrointestinal motility and/or mixing.
40 . A composition comprising:
a bacterial strain or conditioned medium from the bacterial strain, wherein the bacterial strain or conditioned medium from the bacterial strain reduces spontaneous and/or induced transient receptor potential vanilloid 1, TRPV1, activation; and
at least one additional component selected from a group consisting of a pharmaceutically acceptable carrier, a pharmaceutically acceptable diluent, a pharmaceutically acceptable excipient, a foodstuff, a food supplement and another therapeutic agent for use in reducing gastrointestinal pain in a subject, and any combination thereof.
41 . The composition according to claim 40 , wherein the composition comprises said another therapeutic agent and said another therapeutic agent modulates gastrointestinal motility and/or mixing in said subject.
42 . The composition according to claim 40 , wherein the bacterial strain is a lactic acid bacterial strain and the conditioned medium is a conditioned medium from a lactic acid bacterial strain.
43 . The composition according to claim 40 , wherein the bacterial strain is Lactobacillus reuteri and the conditioned medium is a conditioned medium from Lactobacillus reuteri.
44 . The composition according to claim 40 , wherein the bacterial strain is Lactobacillus reuteri DSM 17938 and the conditioned medium is a conditioned medium from Lactobacillus reuteri DSM 17938.
45 . A method of reducing gastrointestinal pain in a subject in need thereof, said method comprising administering an effective amount of the composition of claim 40 .
46 . The method of claim 45 , wherein the bacterial strain is a lactic acid bacterial strain and the conditioned medium is a conditioned medium from a lactic acid bacterial strain.
47 . The method of claim 45 , wherein the bacterial strain is Lactobacillus reuteri and the conditioned medium is a conditioned medium from Lactobacillus reuteri.
48 . The method according to claim 47 , wherein said bacterial strain is Lactobacillus reuteri DSM 17938 and the conditioned medium is a conditioned medium from Lactobacillus reuteri DSM 17938.
49 . The method according to claim 45 , wherein said subject is suffering from an intestinal motility disorder causing said gastrointestinal pain in said subject.
50 . The method according to claim 45 , wherein said subject is suffering from a disease selected from a group consisting of colic, irritable bowel syndrome, constipation causing said gastrointestinal pain in said subject, and any combination thereof.