Electroacupuncture reduces visceral pain and anxiety associated with inflammatory bowel disease by inhibition of vHPC-to-mPFC pathway.

EA effectively treats gastrointestinal diseases, pain symptoms, and emotional disorder. Furthermore, vHPC and mPFC are two of the crucial nuclei involved in controlling chronic pain and anxiety-like behaviors. In the present study, it is investigated whether EA may reduce visceral pain and anxiety associated with inflammatory bowel disease (IBD) by inhibition of vHPC-to-mPFC pathway. We found that EA alleviated visceral hyperalgesia and anxiety in TNBS-treated IBD mice. EA decreased the numbers of c-Fos and neurogranin (labeled glutamatergic neurons) co-labeled neurons in both vHPC and mPFC. EA suppressed the activation of vHPC and mPFC pyramidal neurons associated with anxiety-like behaviors and EA suppressed the activation of vHPC neuronal response to von Frey filament. In addition, chemogenetic inhibition of the vHPC-to-mPFC pathway alleviated mechanical allodynia, visceral hyperalgesia and anxiety in IBD mice. However, chemogenetic activation of vHPC-to-mPFC pathway antagonized the effect of EA on anxiety and visceral hyperalgesia, but not on mechanical allodynia in IBD mice. In conclusion, our findings revealed that vHPC-to-mPFC pathway is involved in the inhibitory effect of EA on anxiety and pain sensitivity in IBD mice. EA may exert anti-anxiety effect via inhibition of vHPC-to-mPFC pathway. Thus, our study provides new information about the cellular circuits mechanisms of the therapeutic effect of EA on the comorbidity of visceral pain and anxiety induced by IBD.