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

Disclosure

Research grant from Boston Scientific Inc. President, Transtimulation Research Inc.

Functional GI Diseases

Functional dyspepsia

and gastroparesis (25%)Irritable

bowel syndrome

(5-20%)

Gastric esophageal

reflux (14%)

Pain is one of major issuesNo medical therapies…

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.

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

Aims

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

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)

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

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.

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

electrode20 min

GD+SCS

ECG recording

Results

SCS reduced visceromotor (EMG) response

**

*, P<0.05 vs. baseline

Both 50 and 100 Hz SCS reduced EMG substantially

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.

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.

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 .