Abstract
Nociceptin/orphanin FQ (N/OFQ), a 17-amino acid neuropeptide structurally similar to opioid peptides, selectively binds to opioid receptor-like (ORL1) receptor, which has the structure related to classical opioid receptors, but it does not bind opioid ligands. The functions of the N/OFQ system are still under active investigation. The N/OFQ, similarly to traditional opioids, produces membrane hyperpolarization through the opening of potassium channels and activation the ORL1 receptor inhibits adenylyl cyclase activity. In the central nervous system, N/OFQ affects feeding, anxiolytic activity, memory and locomotion but particularly influences sensory perception. In the periphery, N/OFQ inhibits neurogenic contractions in various tissues and affects the function of the cardiovascular and renal systems. N/OFQ is localized in the central nervous system in structures related to nociceptive processes and plays a role in peptidergic signaling of the primary afferent neurons which may be particularly relevant to pain control. Many studies have shown that exogenous application of N/OFQ into the central and peripheral nervous system of rats and mice induces both pro- and antinociceptive effects depending on the drug dose, route of administration, pain stimulus or animal species. The aim of the present review was to demonstrate contribution of both central and peripheral ORL1 receptors as well as various ORL1 ligands to the acute nociceptive stimulation and in chronic pain processes, e.g., inflammation and neuropathy. Moreover, intensive search for both agonists and antagonists of ORL1 receptor opened new experimental and therapeutic possibilities. The novel ligands of ORL1 receptor with high potency and selectivity corroborated a well-documented contribution of this receptor to pain perception, and their potential use in clinical practice has been postulated.