A novel method of sacral nerve stimulation for colonic inflammation.

Abstract

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. 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 5Hz, 10seconds on, 90seconds off; (b) to determine the best stimulation position: bilateral, bipolar, and unipolar stimulation; (c) to determine the best stimulation parameters: our 5Hz intermittent stimulation vs 14Hz-210μs 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. 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 5Hz intermittent stimulation but not the 14Hz 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 1hour daily using intermittent 5Hz 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.