Selection of Agents Modulating Gastrointestinal Pain

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.

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.