Blockade of digestion by famotidine pretreatment does not interfere with the opioid-enhancing effect of ingested amniotic fluid.

Ingestion of placenta or amniotic fluid by rats has been shown to enhance ongoing opioid-mediated antinociception, but does not, by itself, produce antinociception. This enhancement is produced by an active substance(s) in placenta and amniotic fluid that we have termed POEF for placental opioid-enhancing factor. Previous research has shown that enhancement requires mediation by the gastrointestinal system: gastric vagotomy blocks enhancement produced by ingested placenta; amniotic fluid injected SC or IP does not produce enhancement. The present study was designed to distinguish between two possible explanations for the blockade of the POEF effect produced by gastric vagotomy: that afferent information arising in vagal gastric receptors conveys the critical information to the CNS, or that disruption of vagal efferent action on digestion blocks the manufacture or activation of the POEF molecule in the gut. Famotidine is an H2-histamine receptor antagonist that reduces gastric acid and pepsin secretion to an extent at least as great as gastric vagotomy. Rats treated with either famotidine or a vehicle were fed placenta or a control substance, then stimulated with vaginal/cervical probing to produce antinociception that is partly opioid mediated. Famotidine did not block POEF enhancement of vaginal/cervical stimulation-induced analgesia in a tail flick latency test. These results suggest that enhancement by POEF does not require normal digestive processes or other processes inhibited by famotidine.