Changes in the tissue concentrations of several neuropeptides in porcine intestines and intestine-innervating ganglia in the course of porcine proliferative enteropathy

Inflammatory processes are associated with changes in the interplay of different pro- and anti-inflammatory factors, including neuropeptides, in tissue. This study was performed to investigate the influence of proliferative enteropathy on the concentration of several neuropeptides known to be involved in the regulation of the inflammatory process in porcine intestine and intestine-innervating ganglia. The concentration of galanin, vasoactive intestinal polypeptide, somatostatin, neuropeptide Y, substance P and calcitonin gene-related peptide were assayed with ELISA in the coeliac-superior mesenteric ganglion, inferior mesenteric ganglion, selected dorsal root ganglia, ileum and the descending colon in healthy and sick pigs. The concentrations of the studied neuropeptides were higher in sick animals. Statistically significant differences were found for coeliac-superior mesenteric ganglion (galanin, vasoactive intestinal polypeptide, somatostatin and neuropeptide Y), inferior mesenteric ganglion (galanin, somatostatin and neuropeptide Y), dorsal root ganglia (galanin, somatostatin, neuropeptide Y and calcitonin gene-related peptide), ileum (galanin and somatostatin) and the descending colon (galanin, somatostatin and neuropeptide Y). The data clearly show the influence of the inflammatory process on the concentration of some of the studied neuropeptides present in inflamed tissues and ganglia innervating the inflamed gut. These changes must be associated with the role the studied neuropeptides play in the inflammatory process.

Enhanced excitability of guinea pig inferior mesenteric ganglion neurons during and following recovery from chemical colitis

Postganglionic sympathetic neurons in the prevertebral ganglia (PVG) provide ongoing inhibitory tone to the gastrointestinal tract and receive innervation from mechanosensory intestinofugal afferent neurons primarily located in the colon and rectum. This study tests the hypothesis that colitis alters the excitability of PVG neurons. Intracellular recording techniques were used to evaluate changes in the electrical properties of inferior mesenteric ganglion (IMG) neurons in the trinitrobenzene sulfonic acid (TNBS) and acetic acid models of guinea pig colitis. Visceromotor IMG neurons were hyperexcitable 12 and 24 h, but not 6 h, post-TNBS during “acute” inflammation. Hyperexcitability persisted at 6 days post-TNBS during “chronic” inflammation, as well as at 56 days post-TNBS when colitis had resolved. In contrast, there was only a modest decrease in the current required to elicit an action potential at 24 h after acetic acid administration. Vasomotor neurons from inflamed preparations exhibited normal excitability. The excitatory effects of XE-991, a blocker of the channel that contributes to the M-type potassium current, and heteropodatoxin-2, a blocker of the channel that contributes to the A-type potassium current, were unchanged in TNBS-inflamed preparations, suggesting that these currents did not contribute to hyperexcitability. Riluzole, an inhibitor of persistent sodium currents, caused tonic visceromotor neurons to accommodate to sustained current pulses, regardless of the inflammatory state of the preparation, and restored a normal rheobase in neurons from TNBS-inflamed preparations but did not alter the rheobase of control preparations, suggesting that enhanced activity of voltage-gated sodium channels may contribute to colitis-induced hyperexcitability. Collectively, these data indicate that enhanced sympathetic drive as a result of hyperexcitable visceromotor neurons may contribute to small bowel dysfunction during colitis.