Interstitial cells of Cajal and inflammation-induced motor dysfunction in the mouse small intestine

Background & Aims: Interstitial cells of Cajal (ICC) play an important role in the control of gastrointestinal motility. We aimed to determine a poten tial role for ICC in the pathophysiology of inflammation-induced motor diso rders. Methods: Effects of Trichinella spiralis infection on electrical pac emaker activity, the structure of ICC associated with Auerbach's plexus, an d in vivo motor patterns were studied in the mouse small intestine. Results : Between days 1 and 15 after infection, structural damage occurred in the network of ICC, particularly in the processes connecting ICC to each other and to smooth muscle cells. This was associated with desynchronization of e lectrical pacemaker activity. Abnormal stow wave activity occurred, includi ng doubling of frequency and electrical quiescence, leading to the developm ent of ectopic pacemaker activity in vivo. In vivo motor patterns in the sm all intestine changed from consistent peristaltic contractile activity in c ontrol animals to periods of quiescence alternating with both orally and ab orally propagating contractile activity in the presence of inflammation. Si xty days after infection, all parameters studied had returned to normal val ues. Conclusions: inflammation-induced alterations in the network of ICC of the small intestine associated with Auerbach's plexus lead to disorganizat ion of motor patterns. Because of the strong temporal correlation between d amage to the ICC network, electrical uncoupling, the appearance of ectopic pacemaker activity, and the occurrence of retrograde peristalsis, it is con cluded that ICC can play a major role in inflammation-induced motor disturb ances.