The enteric nervous system (ENS) regulates stretching and contraction of muscles in the gastrointestinal tract (gut motility), which is critical for digestion. Gastrointestinal disorders resulting from irregular gut motility affect more than a quarter of the world’s population. One method of treating irregular organ function is neurostimulation, in which targeted electrical current is used to stimulate the ENS. However, this method has seen limited success for gastrointestinal disorders, because we don’t understand how electrical stimulation affects the ENS and gut motility. Current computational models that simulate the effects of electrical stimulation of the ENS are incomplete, which makes predicting the effects of different ENS stimulation patterns difficult in living organisms.

In a study funded by the NIH Common Fund SPARC Program, investigators Warren Grill and Xiling Shen developed a computational model of the ENS and used this model to assess neurostimulation strategies for regulating gut motility. The neuromechanical model included a network of parts involved in gut motility - enteric neurons, smooth muscle fibers, and interstitial cells of Cajal (ICCs, cells that act as electrical pacemakers and promote smooth muscle contraction during digestion). The team simulated intestinal tract motility by passing a virtual pellet that stimulates sensory neurons and responds to smooth muscle contractions through the ENS computer model. They found that simulated current pulses at a frequency of 0.5 Hz were more effective at regulating the pacemaker frequency of ICCs, and accelerating gut motility, than higher pulse frequencies that are more commonly used. They validated this model in experiments with rats, in which bead propulsion through the gut was measured during electrical stimulation of the colon and found to behave as predicted from the simulation. The results of this study have implications for the neurostimulation treatment of gastrointestinal disorders resulting from reduced gut motility.

Reference: Electrical stimulation of gut motility guided by an in silico model. Barth, BB, Henriquez, CS, Grill, WM, and Shen, X. Dec 2017. J. Neural Eng. 14(6): 066010.