Opioid Effects on Inflammatory and Regenerative Marker Expression in Rat Intestine

Opioids can have profound effects on the human gastrointestinal system, such as opioid-induced constipation. Conversely, the mammalian intestine is an organ that experiences constant regeneration, which is maintained by intestinal stem cells located in intestinal crypts. However, the exact impact of opioids on intestinal proliferation and regeneration is poorly characterized. This study focused on the effects of opioids on the epithelial regeneration of rat intestines. Specifically, it was examined how oxycodone administration altered inflammatory and regenerative marker genes expression levels. Moreover, in order to address whether oxycodone intoxication and withdrawal led to differential expression, treatment and control cohorts each were split into two groups, one receiving an acute naloxone injection to precipitate withdrawal and the other a saline injection as vehicle control. The mRNA expression levels of the stem cell/regenerative marker Lgr5 and the inflammatory marker IL-6 were analyzed by quantitative reverse transcription PCR. Additionally, we have begun protein-based analyses. We found increased expression levels of IL-6 in the small intestine of oxycodone-treated rats. In contrast, oxycodone administration led to upregulation of Lgr5 in the colon, which appeared to be reduced during naloxone-initiated withdrawal. Our preliminary results show that oxycodone may affect inflammatory and regenerative gene expression in rat intestine. Future analyses will include additional marker genes as well as protein expression detection methods. Furthermore, correlations with opioid-induced gut microbiota changes will be explored.