A bidirectional switch to treat colonic dysmotility

Severe constipation can be life-threatening and disproportionately affects patients who may not benefit from conventional treatments. Sacral nerve stimulation (SNS) is an alternative to laxatives and pharmaceuticals, and it modulates propulsive action in the colon. Conventional SNS failed to treat slow-transit constipation. I hypothesized bursts of nerve stimulation interleaved by quiescent periods increase colonic transit more effectively than continuous nerve stimulation. I electrically stimulated the colon directly in computational models and the isolated mouse colon to characterize properties of the colonic motor complex (CMC), and I used optical and fluorescent imaging, electromyography, and manometry to compare the effect of pelvic and sacral nerve stimulation on colonic motility. I developed a computational model of colonic motility and compared the effects of burst and conventional nerve stimulation on pellet velocity and colonic emptying under normal and slow transit conditions. Burst nerve stimulation evoked more frequent calcium and pressure waves, and increased fecal pellet output than continuous nerve stimulation in the isolated mouse colon, anesthetized rat, and computational model, respectively. Burst nerve stimulation with optimized burst frequency, duration, and interval more effectively produced prokinetic motility than continuous nerve stimulation, suggesting that burst SNS may be a viable clinical treatment for severe and slow transit constipation.