Electroacupuncture Neural Stimulation Mitigates Bladder Dysfunction and Mechanical Allodynia in Cyclophosphamide Induced Cystitis through Downregulation of the BDNF-TrkB Signaling Pathway.

Central sensitization plays a critical role in bladder pain syndrome/interstitial cystitis (BPS/IC). Electroacupuncture (EA) nerve stimulation therapy has been broadly acknowledged as an effective means of alleviating chronic pathological pain. However, it remains to be explored whether EA is effective in mitigating pain-sensitive symptoms of BPS/IC and the mechanisms involved. This study aims to investigate the analgesic effect and mechanism of EA therapy. To achieve this goal, we employed several techniques: mechanical pain threshold tests to assess pain sensitivity, urodynamic studies to evaluate bladder function, Western blotting (WB) for protein analysis, immunofluorescence for visualizing, and transcriptomics. A rat cystitis model was established through a systemic intraperitoneal injection with cyclophosphamide (CYP). EA therapy was executed by stimulating the deep part of the hypochondriac point, where the 2nd-4th sacral nerves traverse. EA treatment was observed to effectively reduce mechanical allodynia, enhance urinary function, suppress the activation of microglial cells, and alleviate neuroinflammation. Additionally, EA demonstrated the capability to downregulate BDNF-TrkB signal transduction in the spinal dorsal horn. Transcriptome sequencing has indicated that EA therapy potentially inhibits excitatory neural transmission and modulates several pathways related to longevity. Furthermore, EA therapy has shown efficacy in treating conditions such as Huntington's disease, amyotrophic lateral sclerosis, and prion diseases. In conclusion, by regulating the BDNF-TrkB signaling, EA nerve stimulation can effectively alleviate bladder dysfunction and mechanical allodynia in cyclophosphamide-induced cystitis model. Our research elucidates the underlying mechanisms of EA therapy in treating bladder dysfunction and offers new theoretical insights for addressing painful sensitization in BPS.