Centrally Administered Nociceptin/Orphanin FQ and the Neuroprotective Effect of Electroacupuncture Against Cerebral Ischemia Following Middle Cerebral Artery Occlusion/Reperfusion in Rats

Background: Nociceptin/orphanin FQ (N/OFQ) is a non-classical opioid peptide that has extensive physiological functions including regulating cerebral circulation. But the impact of these regulations in cerebral ischemia is unknown. Objective: To observe the effects of N/OFQ on the infarction volume and effects of electroacupuncture (EA) against cerebral ischemia. Design, Setting, and Subjects: A randomized controlled animal experiment of 62 male rats with a middle cerebral artery occlusion. The study was conducted at the Department of Neurology, The Second Affiliated Hospital of Qingdao University Medical College, People's Republic of China. Intervention: The rats were randomly assigned to 1 of 9 groups (3 intracerebroventrical N/OFQ at different dosages, 3 EA with or without additional intervention, and 3 varying control groups). Main Outcome Measure: The somatosensory evoked potential and the brain infarct volume were observed. Results: P1 amplitude of the evoked potential decreased with the latency unchanged after middle cerebral artery occlusion. The N/OFQ dosage of 0.1 mu g centrally administered had no effect but 1 or 10 mg of N/OFQ aggravated the ischemic evoked potential. The decreased evoked potential restored at 1 hour postreperfusion of the artery, but 1 and 10 mg of N/OFQ slowed the recoveries, and 10 mg of N/OFQ postponed evoked potential recovery until 3 hours after reperfusion. Somatosensory evoked potential responses to N/OFQ showed a doseeffect response. Both 1 and 10 mg of N/OFQ enlarged the brain infarct volume. EA decreased the infarction volume; however, the brain infarction volume in the EA+N/OFQ group was larger than that in EA+ACSF (artificial cerebrospinal fluid) group (P< .01). Conclusions: This study provides pathological evidence of the effect of N/OFQ centrally administered on the cerebral circulation, which aggravated the focal cerebral ischemia in a rat occlusion model. EA improved the somatosensory evoked potential and reduced the brain infarction volume, but this effect was blocked by N/OFQ.