Abstract
Cellular actions of nociceptin/orphanin FQ (N/OFQ) resemble those of μ-, δ-, and κ-opioids, i.e. activation of inwardly rectifying K + conductance, inhibition of high-voltage-activated Ca 2+ channel currents, and impediment of neurotransmitter release. Differences in ORL 1 and μ-receptor distribution lead to: 1) more widespread actions of N/OFQ on periaqueductal gray neurons than opioids and 2) differential effects of N/OFQ and opioids in the brainstem. Also, unlike opioids, N/OFQ inhibits T-type Ca 2+ channel current in sensory neurons. Opioids and N/OFQ may modulate glutamate responses in different ways, and certain actions of N/OFQ are potentiated following nerve injury whereas those of μ-opioids are attenuated. Agonists at ORL 1 receptors may therefore be of clinical interest in the management of neuropathic pain.
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