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• W2887932055 abstract "Abstract Background Sustained pain hypersensitivity is the hallmark of stressed colon which could be partially explained by central sensitization with synaptic plasticity, the key mechanism of memory. We previously identified that synaptic plasticity of enteric nerve system (ENS) contributed to peripheral pain maintaining in the gut. However, the mechanisms of enteric “memory” formation remain elusive. Methods In this study, rats were exposed to water avoidance stress (WAS) or sham stress (SS), with cromolyn sodium or physiological saline injected intraperitoneally 30 minutes before stress every day. The abdominal withdrawal reflex scores, mesenteric afferent nerve activity, enteric neural c‐fos expression, and enteric synaptic plasticity were assessed, and mast cell infiltration and degranulation. Furthermore, colonic mucosal mediators‐induced enteric synaptic plasticity and the role of mast cell‐derived nerve growth factor (NGF), tryptase, and histamine were investigated via ex vivo longitudinal muscle‐myenteric plexus (LMMP) organotypic culture. Key Results It is shown that mast cell stabilizing inhibited WAS‐induced visceral hypersensitivity through enhancing visceral pain threshold, decreasing spontaneous and distention‐induced mesenteric afferent firing, and downregulating enteric neural activation ( c‐fos ). Importantly, WAS led to evident enteric synaptic plasticity, but decreased by cromolyn. Water avoidance stress‐derived mucosal supernatants markedly enhanced the c‐fos expression and enteric synaptic plasticity in LMMP tissues, which could be eliminated by mast cell inhibition or NGF neutralization, but not tryptase or histamine blocking. Conclusions & Inferences In conclusion, mast cells/NGF pathway may be the key regulator of synaptic plasticity of ENS and participate in the formation of chronic stress‐induced sustained visceral hypersensitivity." @default.
• W2887932055 created "2018-08-22" @default.
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• W2887932055 date "2018-08-01" @default.
• W2887932055 modified "2023-10-14" @default.
• W2887932055 title "Sustained pain hypersensitivity in the stressed colon: Role of mast cell‐derived nerve growth factor‐mediated enteric synaptic plasticity" @default.
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• W2887932055 doi "https://doi.org/10.1111/nmo.13430" @default.
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