Cellular neurophysiological actions of nociceptin/orphanin FQ

Cellular actions of nociceptin/orphanin FQ (N/OFQ) resemble those of mu-, d elta-, and kappa-opioids, i.e. activation of inwardly rectifying K+ conduct ance, inhibition of high-voltage-activated Ca2+ channel currents, and imped iment of neurotransmitter release. Differences in ORL1 and mu-receptor dist ribution lead to: 1) more widespread actions of N/OFQ on periaqueductal gra y neurons than opioids acid 2) differential effects of N/OFQ and opioids in the brainstem. Also, unlike opioids, N/OFQ inhibits T-type Ca2+ channel cu rrent in sensory neurons. Opioids and N/OFQ may modulate glutamate response s in different ways, and certain actions of N/OFQ are potentiated following nerve injury whereas those of mu-opioids are attenuated. Agonists at ORL, receptors may therefore be of clinical interest in the management of neurop athic pain. (C) 2000 Elsevier Science Inc. All rights reserved.