1. Spinal Cord Electrical Stimulation for Visceral Hypersensitivity in a Rodent Model of Functional Dyspepsia Geng-Qing Song and Jiande Chen Veterans Research Foundation, VA Medical Center, Oklahoma City, OK, USA and Division of Gastroenterology University of Texas Medical Branch, Galveston

2. Disclosure  Research grant from Boston Scientific Inc.  President, Transtimulation Research Inc.

3. Functional GI Diseases Functional dyspepsia and gastroparesis (25%) Irritable bowel syndrome (5-20%) Gastric esophageal reflux (14%) Pain is one of major issues No medical therapies…

4. SCS for Visceral Pain  Visceral pain is common in patients with functional GI diseases; no effective medication therapies  Few animal and human studies have explored potential of SCS for IBS with promising but limited data  FD and gastroparesis are common; visceral pain and gastric hypomotility are major pathological factors in FD  SCS has been reported to improve gastric motility due to its inhibitory effect on sympathetic activity.

5. SCS Improved Gastric Emptying of Solids in both Regular and Diabetic Rats

6. Aims To assess the SCS effects on visceral pain in a rodent model of FD with gastric hyperalgesia.

7. Rodent Model of FD with gastric hypersensitivity  FD rats: 10 days old SD received 0.2 ml 0.1% iodoacetamide (IA) in 2% sucrose daily for 6 days and were then allowed to grow adult age (8-11 weeks)

8. Animal Preparation  SCS electrodes: epidural space at T9/T10  EMG electrodes: at the neck  Gastric balloon: for gastric distention.  SCS parameters: 50/100 Hz ; 0.2 ms; 90% of the motor threshold

9. Exp.1: Effects of SCS on Gastric Hypersensitivity EMG Control Recovery 20 min SCS EMG+SCS  Gastric balloon was rapidly inflated to 20, 40, 60, and 80 mmHg for a 20-s stimulation period followed by a 2- min rest and then the procedure was repeated for one more time.

10. Exp.2: Effects of SCS on Autonomic Function 20 min Baseline 20 min GD 20 min SCS  An electrocardiogram (ECG) was recorded.  Autonomic functions were assessed by the spectral analysis of the heart rate variability which was derived from the ECG.  Blood samples were taken for norepineprine (NE)  SCS parameters: 0.2ms/50Hz with 90% MT. Two recording electrodes One reference electrode 20 min GD+SCS ECG recording

11. Results

12. SCS reduced visceromotor (EMG) response * * *, P<0.05 vs. baseline Both 50 and 100 Hz SCS reduced EMG substantially

13. Effects of FD and SCS on sympathovagal balance * (P<0.05 vs. baseline); ** (P<0.05 vs. the corresponding GD) * ** FD rats showed a significant increase in sympathovagal ratio during GD, this was inhibited by SCS.

14. SCS suppressed GD-induced NE increase * (P<0.05 vs. control and baseline); ** (P<0.05 vs. control and the corresponding GD) * ** * * FD rats showed a significant increase in NE during GD, this was inhibited by SCS.

15. Conclusions  SCS at T9-T10 with appropriate parameters ameliorates gastric hyperalgesia induced by GD in a rodent model of FD by inhibiting sympathetic activity.  Combined with its prokinetic effect shown before, SCS may be a potential therapy for functional dyspepsia.  More efforts should be made to explore GI applications of SCS.