Nociceptin

Nociceptin, or nociceptin/orphanin FQ (N/OFQ), is a neuropeptide that serves as the endogenous ligand for the nociceptin receptor (OPRL1; ORL1). It is produced from the PNOC gene as part of the larger prepronociceptin precursor. The receptor is a G protein-coupled receptor that mainly signals through Gi/o proteins, inhibiting adenylyl cyclase and altering ion channels to decrease neuronal excitability.

The nociceptin system participates in pain modulation at spinal and supraspinal levels. N/OFQ can produce analgesia in some settings, but can also facilitate pain in others, depending on the brain region, dose, and model. It interacts with other opioid systems and can influence morphine analgesia.

Beyond pain, N/OFQ modulates stress and anxiety, learning and memory, feeding and energy homeostasis, and neuroendocrine and autonomic functions. It also affects reward pathways and may influence addictive behaviors, as well as inflammatory and immune processes.

Anatomically, PNOC is expressed in several brain areas, including the hypothalamus, amygdala, periaqueductal gray, and brainstem, with additional expression in peripheral tissues. N/OFQ is conserved across mammals and can be detected in various bodily fluids.

Discovery: Orphanin FQ was identified in 1995 as the endogenous ligand for the orphan receptor later named ORL1; the ligand was subsequently renamed nociceptin/orphanin FQ.