Nematode-induced Jejunal Inflammation in the Ferret Causes Long-term Changes in Excitatory Neuromuscular Responses

Enteric infections in animals and humans have proven the link between mucosal inflammation and gastrointestinal motor dysfunction. The goal of the present investigation was to study the long-term effects of mucosal inflammation on the neuromuscular functions of the small intestine in a ferret model of primary Trichinella spiralis infection. Myeloperoxidase activity and isometric contractions of isolated jejunal muscles were studied on days 8, 30, and 60 postinfection (PI). The peak increase in myeloperoxidase activity seen on day 8 PI returned to normal levels by day 60 PI. Contractions of the longitudinal and circular muscles evoked by electrical field stimulation of enteric nerves on day 8 PI showed no difference when compared with uninfected controls. However, during this enteric phase of the infection, neurally mediated responses were characterized by a disturbance in the balance between cholinergic and nonadrenergic, noncholinergic (NANC) excitation with both a reduction of cholinergic and a reciprocal enhancement of NANC neurotransmission. On days 30 and 60 PI the amplitude of neurally mediated responses and the balance between cholinergic and NANC excitation were restored in the circular but not in the longitudinal muscle. In addition, there were changes in the effector function involving smooth muscle hyperresponsiveness to high K+ or carbachol on days 8, 30, and 60 PI. However, a significant reduction in EC50 for carbachol was found only on day 60 PI. The results demonstrate that T. spiralis infection results in alterations of muscle contractility and enteric neurotransmission that persist after the resolution of mucosal inflammation.