The purpose of this study was to determine effects and mechanisms of sacral nerve stimulation (SNS) on visceral hypersensitivity in rodent models of colonic hypersensitivity. SNS was performed with different sets of parameters for 30 min in six regular rats. Visceral sensitivity was assessed by the measurement of electromyogram and abdominal withdrawal reflex before and after SNS. Real/sham SNS with optimized parameters was performed in 8 restraint stress-induced visceral hypersensitivity rats and 10 neonatal acetic acid-treated colonic hypersensitivity rats; acute effect of SNS was assessed by comparing electromyogram and heart rate variability. Neonatal acetic acid-treated rats were treated by SNS (n = 10) or sham-SNS (n = 10) daily for seven days for the assessment of the chronic effect of SNS. (1) When the stimulation amplitude was reduced from 90% of motor threshold to 65% or 40% motor threshold, SNS with certain parameters showed an inhibitory effect on abdominal withdrawal reflex. The best stimulation parameters for SNS were “14 Hz, 330 µs, and 40% motor threshold.” (2) SNS significantly reduced visceral hypersensitivity and improved autonomic function in restraint stress-induced rats. The inhibitory effect was blocked by naloxone. (3)Acute and chronic SNS significantly reduced visceral hypersensitivity and improved autonomic function in acetic acid-treated rats. SNS with reduced stimulation strength may be used to treat colonic hypersensitivity and the best stimulation parameters seem to be “14 Hz, 330 µs and 40% motor threshold”. SNS with optimized parameters improved visceral hypersensitivity in rodent models of colonic hypersensitivity mediated via the autonomic and opioid mechanisms.

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.

This study aims to investigate the role of transcutaneous neuromodulation (TN) on the regulation of gastrointestinal hormones and bile acids in patients with functional constipation (FC). Twenty FC patients were treated with TN for four weeks. The effects of TN on symptoms were evaluated by questionnaires. Plasma levels of serotonin (5-HT), motilin, somatostatin, and vasoactive intestinal peptide (VIP) were measured by ELISA and 12 individual bile acids assayed by liquid chromatography tandem mass spectrometry. Results were as follows. (1) TN treatment increased the frequency of spontaneous bowel movement, improved the Bristol Stool Score, and reduced Patient Assessment of Constipation Symptom score and Patient Assessment of Constipation Quality of Life score. (2) FC patients showed decreased plasma levels of 5-HT, motilin, and VIP and an increased plasma level of somatostatin (P < 0.05). Four-week TN treatment increased plasma levels of 5-HT and motilin and decreased the plasma level of somatostatin in the FC patients (P < 0.05). (3) Taurocholic deoxycholate, taurocholic acid, and taurocholic lithocholic acid were increased in the FC patients (P < 0.005) but reduced by TN treatment (P < 0.05). This study has suggested that the therapy may improve the symptoms of FC by alleviating the disorders of gastrointestinal hormones and bile acids.

Background/AimsIn a recent study of sacral nerve stimulation (SNS) for colonic inflammation, a possible spinal‐vagal pathway was implicated. The aim of this study was to provide evidence for such a pathway by investigating the effects of SNS on dysmotility of the stomach and duodenum that are not directly innervated by the sacral efferents.MethodsTwenty‐seven rats were chronically implanted with wire electrodes for SNS and gastrointestinal slow waves. SNS was performed in several acute sessions to investigate its effects on gastric/duodenal slow waves and emptying/transit impaired by glucagon and rectal distention (RD).Results(a) SNS increased the percentage of normal gastric slow waves impaired by glucagon (from 53.9% to 77.0%, P < .0001) and RD (from 64% to 78%, P = .037). This improvement was abolished by atropine. (b) Similar effects were observed with SNS on duodenal slow waves, which was also blocked by atropine. (c) SNS normalized delayed gastric emptying induced by glucagon (control: 61.3%, glucagon: 44.3%, glucagon + SNS: 65.8%) and RD (control: 61.3%, RD: 46.7%, RD + SNS: 64.3%). It also normalized small intestinal transit delayed by RD (P = .001, RD + SNS vs RD; P = .9, RD + SNS vs control). (4) Both glucagon and RD induced an increase in the sympathovagal ratio (P = .007, glucagon vs baseline; P < .001, RD vs baseline) and SNS decreased the ratio (P = .006, glucagon + SNS vs glucagon; P = .04, RD + SNS vs RD).ConclusionsNeuromodulation of the sacral nerve improves gastric and small intestinal pacemaking activity and transit impaired by glucagon and RD by normalizing the sympathovagal balance via a retrograde neural pathway from the sacral nerve to vagal efferents.