Effects of continuous microchip (MC) vagal neuromodulation on gastrointestinal function in rats.

Afferent fibers from gastrointestinal tract outnumber efferents ten times in vagal nerves. Modifying the afferent input makes possible to change discharge of vagal efferents affecting gastrointestinal functions in process known as neuromodulation (NM). Lately it has been used in the treatment of pain and hyperactive neurogenic bladder in urology. MC induced NM may therefore provide a concurrent to pharmacology tool, in treatment of gastrointestinal disorders. The aim of this study was to investigate the effects of long term neuromodulation procedure with use of MC on gastric motility, secretion and weight control in conscious rats. Experiments were performed on 30 Wistar male rats (250-350 g) divided in two groups: sham operated and microsurgically implanted with MC on left vagal nerve below diaphragm. Following stimulation parameters were used: frequency of 0.5-30 Hz, amplitude of 0.55 V, impulse duration of 10 ms in monophasic fashion. In both groups food intake and body weight were measured through the period of 2 weeks after recovery period. Then gastric fistula was implanted in gastric antrum and fasted gastric motility recorded with use of PowerLab system (Australia). Gastric emptying and secretion were also tested with use of phenol red and automatic titration methods. On the daily basis glucose level with standard test and leptin after MC implantation were measured. Recording of vagal activity in fasted rats showed burst of action potentials about 5 +/- 2.5 in period of 5000 sec, each burst with spike frequency up to 35 Hz. Food (5 ml of Intralipid--intragastrically) almost doubled amount of bursts to 12 +/- 5 in period of 5000 sec with increase in frequency at spike up to 50 Hz. MC induced vagal activity showed continuous spike activity similar to fed pattern. MC induced NM decreases daily food intake by 6% (33.6 +/- 4.8 vs control 35.5 +/- 4.8 g, p < 0.01). Body weight gain in rats before MC implantation decreased by 20% within 2 weeks after recovery (34.8 +/- 9.08 vs control 23.56 +/- 4.15 g). Fasting control glucose level also decreased of 5.5% (93.15 +/- 9.3 vs control 98.5 +/- 11.2 mg%, p < 0.05). Frequency of gastric contractions did not change significantly in MC versus control but amplitude of contractions increased of about 66.7% (2.0 +/- 0.8 vs 1.17 +/- 0.52) at the dominant frequency 0.08 Hz range and about 71.5% (1.17 +/- 0.35 vs 0.68 +/- 0.47, p < 0.05) at the frequency 0.12 Hz. in FFT analysis PowerLab (chart v = 4.01). BAO decreased by 29.25% without H+ concentration changes (0.2 +/- 0.14 vs 0.14 +/- 0.12 mmol/30 min, p < 0.05) but MAO did not change in MC rats (0.37 +/- 0.25 vs 0.42 +/- 0.28 mmol/30 min, p 0.05). Gastric emptying of isotonic solution increased by 10% (90.46 +/- 5.34 vs 80.39 +/- 9.95) percent of marker passing to duodenum/5 min, p < 0.0001). Our results suggest that MC induced NM affect brain-gut axis via influencing metabolic and gastric function and decreases body weight.