Using Electrical Bursts to Get the Gut Moving

Biomedical engineers at Duke University have demonstrated a new nerve stimulation technique that relieves constipation. By stimulating the sacral nerve using a pattern of electrical bursts, the team showed they could regulate the movement of the colon to effectively treat constipation in rats.

The technique, which was recently licensed by Boston Scientific, is described in a paper published November 5 in the journal Science Translational Medicine.

Much like breathing, digestion happens subconsciously thanks to signaling through the parasympathetic nervous system—a portion of the “autonomic” nervous system that controls many bodily functions without conscious thought. Two of the main centers of this system are the vagus nerve, which controls organs in the chest and upper abdomen, and the sacral nerves, which control organs in the pelvic region.

When lines of communication between the brain and these critical nerve centers break down, a wide variety of gastrointestinal disorders can occur. While most can be treated through traditional medications or electrical stimulation, colonic dysmotility, one of the primary causes of constipation, has remained challenging.

“We know that electrically stimulating the sacral nerves can both increase and decrease the movement of the colon,” said Warren Grill, the James B. Duke Distinguished Professor of Biomedical Engineering. “The pervading practice was to use the stimulation parameters to treat both incontinence and constipation, but we’ve seen clinically that that parameters that effectively treat chronic diarrhea are not effective at treating constipation.”  

Bradley Barth, a former PhD student in the Grill lab, had a hypothesis as to why. During earlier work, the duo found that muscles in the gut experience a recovery period after contracting, which could last anywhere from five to fifteen seconds. This meant that there was a window of time when the tissue was unable to contract, even in response to additional stimulation.  

Existing electrical stimulation therapies for gut-related issues often use a continuous train of electric pulses. Based on their previous work, Barth and Grill realized that this constant stimulation was not giving the gut muscles enough time to recover, which could slow them down and even make constipation worse.

To get around this challenge, the team developed a pattern of electrical stimulation with intermittent bursts. They then tested this pattern using a combination of computer models, colon tissue samples, and animal models. The results showed that stimulation delivered in these patterned bursts was much more effective at treating constipation in rats compared to standard constant stimulation.

Barth and Grill then went further, systematically testing variations of stimulation frequency, stimulation duration, and the time between electrical bursts to determine the minimum effective parameters needed to relieve constipation. This work provides guidelines as to how these stimulation pattern might be used clinically in human patients. The initial results caught the eye of industry experts at Axonics, a company that uses neuromodulation techniques and implants to treat overactive bladder and incontinence. The company established a sponsored research agreement with Grill and his team to determine how they could incorporate burst-pattern stimulation into their existing devices. Shortly after this initial work was finished, Axonics was acquired by Boston Scientific, which licensed the intellectual property.

“Our mantra in the lab is ‘from understanding comes innovation,’ and this discovery of the time it takes gut muscles to recover from stimulation and the subsequent development of burst-patterned stimulation is an example of that approach in practice,” said Grill.

“We can incorporate these burst-patterned stimulation parameters into existing implanted pulse generators by reprogramming them to provide patients with more effective therapy without additional surgery,” added Barth. “These sacral nerve stimulation devices have already been in use for over 20 years for issues like incontinence and over-active bladder, so the associated risks are well characterized and the barriers to adopting our novel stimulation programming is low.”

Beyond potential industry collaborations, Grill and Barth are also interested in exploring their stimulation patterns in larger animal models and establishing clinical collaborations to continue to test and improve the technology for diverse patient populations.

“We see a lot of overlap in patient populations between incontinence and constipation, and many patients deal with changing and sometimes contradictory symptoms,” Barth said. “There’s a lot of potential to translate this work into an effective therapy, especially if we can reprogram the same device to treat the specific symptoms a patient may be experiencing at any given time.”

This work was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK119795), by the Department of Biomedical Engineering at Duke University, and by Axonics, Inc. in the form of a sponsored research agreement.

Bradley Barth and Warren Grill are inventors of licensed patent applications (application number 19/275,099 entitled Systems and methods related to neuromodulation of gastrointestinal dysmotility), owned by Duke University, and they and Duke University have and may continue to receive royalty payments from this licensed intellectual property.

Bradley B. Barth, Warren M. Grill, “Burst-patterned stimulation restores colonic motility in preclinical models.” Science Translational Medicine. November 5, 2025 .DOI:10.1126/scitranslmed.adu4615