Influence of nifedypine on the hyperalgesic action of duodenal distention in sheep.

The aim of this study was to determine the influence of nifedypine--competitive antagonist of voltage-gated dependent L-type Ca2+ channels (VGCCs)--on inhibition of reticulo-ruminal motility, heart beats, respiratory rates and other nociceptive behavior symptoms caused by duodenal distention (DD). The animals, which were under general anesthesia, had duodenal and ruminal fistulas and intracerebroventriculary (i.c.v.) cannulas inserted into the lateral ventricle. Reticulo-ruminal contractions were recorded mechanographically using an electronic tensometer. The frequency of reticulo-ruminal contractions was determined by the number of mechanograms with 5 min intervals prior to and after DD (for 180 min). The duodenal distention was performed using a rubber balloon (10 cm length), which was inserted via the duodenal fistula and filled with 40 ml water. Five min DD caused immediate and almost complete inhibition of reticulo-ruminal contractions, nociceptive behavior symptoms, tachycardia and hyperventilation. Nifedypine per se did not change the reticulo-ruminal motility, general behavior or clinical symptoms; however, doses of 1 and 2 mg of nifedypine in toto infused i.c.v 10 minutes before DD prevented all signs of reticulo-ruminal disorders, as well as the general nociceptive behavior. Nifedypine inhibited particularly clinical symptoms such as tachycardia and hyperventilation. The observed antinociceptive action of VGCCs type-L blockers suggests that these channels play a crucial role in the modulation of acute visceral hyperalgesia. Nifedipine can be useful in controlling acute visceral pain associated, for example, with different kinds of colic.