Role of NOC/oFQ in impaired opioid-induced pial artery dilation following brain injury

Abstract

Previous studies in piglets show that opioid-induced pial artery dilation was impaired following fluid percussion brain injury (FPI). This study was designed to determine the role of the newly described opioid nociceptin orphanin FQ (NOC/oFQ) in such impaired dilation to other opioids after FPI. CSF NOC/oFQ concentration was elevated from 70±6 to 444±56 pg/ml (≈10 −10 M) within 1 h of FPI. Coadministration of NOC/oFQ (10 −10 M) with methionine enkephalin (10 −10, 10 −8, 10 −6 M) attenuated pial dilation induced by this opioid (7±1, 13±2, and 19±2 vs. 2±1, 6±1, and 7±2%) under non-brain injury conditions. Similar inhibition by NOC/oFQ was observed for leucine enkephalin and dynorphin. Methionine enkephalin (10 −10, 10 −8, 10 −6 M)-induced pial artery dilation was also inhibited within 1 h of FPI, but such responses were partially restored in animals pretreated with the NOC/oFQ receptor antagonist [F/G] NOC/oFQ (1–13) NH 2 (10 −6 M) (8±1, 14±1, and 21±1 vs. 1±1, 3±1, and 4±1 vs. 7±1, 11±1, and 17±1% for sham control, FPI and FPI pretreated with the NOC/oFQ receptor antagonist). Leucine enkephalin and dynorphin-induced pial artery dilation were similarly altered by FPI and partially restored by [F/G] NOC/oFQ (1–13) NH 2. These data indicate that the NOC/oFQ released by FPI contributes to impaired dilation to other opioids observed following this insult.