The @entity4412 channel in rodents is a major target for antinociceptive effect of the probiotic XXXX DSM 17938.

@entity1 @entity2951 @entity4412 @entity19 @entity141 @entity10263 @entity6374 @entity71149 @entity356 @entity158 @entity460 @entity35 @entity1168 @entity9854
Certain probiotic bacteria have been shown to reduce distension-dependent gut @entity158 , but the mechanisms involved remain obscure. Live luminal @entity6374 (DSM 17938) and its conditioned medium dose dependently reduced jejunal spinal nerve firing evoked by distension or @entity2951 , and 80% of this response was blocked by a specific @entity4412 channel antagonist or in @entity4412 knockout @entity19 . The specificity of DSM action on @entity4412 was further confirmed by its inhibition of @entity2951 -induced intracellular @entity460 increases in dorsal root ganglion neurons. Another @entity10263 with ability to reduce gut @entity158 did not modify this response. Prior feeding of @entity35 with @entity9854 inhibited the @entity1168 induced by @entity158 . These results offer a system for the screening of new and improved candidate bacteria that may be useful as novel therapeutic adjuncts in gut @entity158 . Certain bacteria exert visceral antinociceptive activity, but the mechanisms involved are not determined. @entity6374 DSM 17938 was examined since it may be antinociceptive in @entity1 . Since transient receptor potential vanilloid 1 ( @entity4412 ) channel activity may mediate nociceptive signals, we hypothesized that @entity4412 current is inhibited by DSM. We tested this by examining the effect of DSM on the firing frequency of spinal nerve fibres in @entity19 jejunal mesenteric nerve bundles following serosal application of @entity2951 . We also measured the effects of DSM on @entity2951 -evoked increase in intracellular @entity141 or ionic current in dorsal root ganglion (DRG) neurons. Furthermore, we tested the in vivo antinociceptive effects of oral DSM on @entity356 in @entity35 . Live DSM reduced the response of @entity2951 - and distension-evoked firing of spinal nerve action potentials (238    27.5% vs. 129    17%). DSM also reduced the @entity2951 -evoked @entity4412 ionic current in DRG neuronal primary culture from 83    11% to 41    8% of the initial response to @entity2951 only. Another @entity10263 ( @entity10263 JB-1) with known visceral anti-nociceptive activity did not have these effects. DSM also inhibited @entity2951 -evoked @entity141 increase in DRG neurons; an increase in @entity141 fluorescence intensity ratio of 2.36    0.31 evoked by @entity2951 was reduced to 1.25    0.04. DSM releasable products (conditioned medium) mimicked DSM inhibition of @entity2951 -evoked excitability. The @entity4412 antagonist @entity71149 or the use of @entity4412 knock-out @entity19 revealed that @entity4412 channels mediate about 80% of the inhibitory effect of DSM on mesenteric nerve response to high intensity gut distension. Finally, feeding with DSM inhibited perception in @entity35 of @entity158 . Our results identify a specific target channel for a probiotic with potential therapeutic properties.
