Nociceptin/Orphanin FQ Modulates Cortical Activity and Trigeminal Nociception

Alterations in the levels of nociceptin/orphanin FQ (N/OFQ) have been reported in patients with primary headaches, including migraines and cluster headaches. These clinical observations suggest that N/OFQ is involved in the pathogenesis of primary headaches.The present study was conducted to determine the role of N/OFQ in the control of trigeminal nociception and cortical excitation.Cortical spreading depression (CSD) was elicited in Wistar rats by cortical application of potassium chloride, and electrocorticograms were recorded. N/OFQ was administered via an intracisternal injection. The presence of CSD-evoked trigeminal nociception was determined with Fos and transient receptor potential vanilloid 1 (TRPV1) immunoreactivity.Nociceptin/orphanin FQ produced a biphasic effect on CSD generation, characterized by an initial attenuation followed by delayed potentiation. The amplitude of CSD waves were lower in the initial period but increased in the later period. The total number of CSD waves recorded in 1 hour was greater in the N/OFQ-treated group. Exposure to N/OFQ significantly increased the number of Fos-immunoreactive cells in the trigeminal nucleus caudalis and the number of TRPV1-immunoreactive cells in the trigeminal ganglia, indicating the enhancement of trigeminal nociception.These results indicate that N/OFQ can lead to biphasic effect characterized by an initial inhibition, and delay potentiation that eventually intensify CSD-evoked trigeminal nociception.