Mechanisms of disease: the pathological basis of gastroparesis--a review of experimental and clinical studies.

The pathogenesis of gastroparesis is complicated and poorly understood. This lack of understanding remains a major impediment to the development of effective therapies for this condition. Most of the scientific information available on the pathogenesis of gastroparesis has been derived from experimental studies of diabetes in animals. These studies suggest that the disease process can affect nerves (particularly those producing nitric oxide, but also the vagus nerve), interstitial cells of Cajal and smooth muscle. By contrast, human data are sparse, outdated and generally inadequate for the validation of data obtained from experimental models. The available data do, however, suggest that multiple cellular targets are involved. In practice, though, symptoms seldom correlate with objective measures of gastric function and there is still a lot to learn about the pathophysiology of gastroparesis. Future studies should focus on understanding the molecular pathways that lead to gastric dysfunction, in animal models and in humans, and pave the way for the development of rational therapies.