A novel method of sacral nerve stimulation for colonic inflammation

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Abstract
Background: Vagal nerve stimulation has been reported to treat inflammation with promising results. The aims of our study were to optimize sacral nerve stimulation (SNS) methodologies for colonic inflammation in a rodent model of colitis and to investigate autonomic and cytokine mechanisms.Methods: Three major efforts were made in optimizing SNS: (a) to determine the best stimulation duration: SNS‐0.5h daily, SNS‐1h daily, and SNS‐3h daily with the parameters set at 5 Hz, 10 seconds on, 90 seconds off; (b) to determine the best stimulation position: bilateral, bipolar, and unipolar stimulation; (c) to determine the best stimulation parameters: our 5 Hz intermittent stimulation vs 14 Hz‐210 μs continuous stimulation. Inflammatory responses were assessed by the disease activity index (DAI), histological analyses, and the myeloperoxidase (MPO) activity. Levels of inflammatory cytokines, norepinephrine (NE), and pancreatic polypeptide (PP) in both plasma and colon tissues were assessed.Key Results: Both SNS‐1h and SNS‐3h significantly ameliorated intestinal inflammation; SNS‐1h was superior to SNS‐3h. Bipolar but not bilateral or unipolar stimulation improved the inflammation in colitis. SNS with 5 Hz intermittent stimulation but not the 14 Hz continuous SNS was better for treating colitis in rats. SNS with the optimized stimulation parameters increased vagal activity and decreased sympathetic activity.Conclusion & Inferences: Bipolar stimulation for 1 hour daily using intermittent 5 Hz parameters is most effective in improving colonic inflammation in TNBS‐treated rats by inhibiting pro‐inflammatory cytokines and increasing anti‐inflammatory cytokines via the modulation of the autonomic function.
Funding Information
  • Defense Advanced Research Projects Agency (N66001‐15‐2‐4059)

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