Nociceptin or orphanin FQ, a 17 amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 neuropeptide

Neuropeptide

Neuropeptides are small protein-like molecules used by neurons to communicate with each other. They are neuronal signaling molecules, influence the activity of the brain in specific ways and are thus involved in particular brain functions, like analgesia, reward, food intake, learning and...

, is the endogenous ligand

Ligand

In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...

 for the nociceptin receptor

Nociceptin receptor

The nociceptin receptor or NOP also known as the orphanin FQ receptor or kappa-type 3 opioid receptor is a protein that in humans is encoded by the OPRL1 gene. The nociceptin receptor is a G protein-coupled receptor whose natural ligand is known as nociceptin or orphanin FQ, a 17 amino acid...

 (NOP, ORL-1). It is derived from the prepronociceptin protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

, as are a further 2 peptides, nocistatin & NocII. The gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 coding for prepronociceptin is located on Ch8p21 in humans.

Nociceptin is an opioid-related peptide

Peptide

Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

, but it does not act at the classic opioid receptors and its actions are not antagonized by the opioid

Opioid

An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...

 antagonist

Receptor antagonist

A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

 naloxone

Naloxone

Naloxone is an opioid antagonist drug developed by Sankyo in the 1960s. Naloxone is a drug used to counter the effects of opiate overdose, for example heroin or morphine overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory...

. Nociceptin is a potent anti-analgesic

Analgesic

An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....

. Nociceptin is widely distributed in the CNS

Central nervous system

The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

; it is found in many regions of the hypothalamus

Hypothalamus

The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

, brainstem, and forebrain

Prosencephalon

In the anatomy of the brain of vertebrates, the prosencephalon is the rostral-most portion of the brain. The prosencephalon, the mesencephalon , and rhombencephalon are the three primary portions of the brain during early development of the central nervous system...

, as well as in the ventral horn

Anterior horn (spinal cord)

The anterior horn of the spinal cord is the ventral grey matter section of the spinal cord. The anterior horn contains motor neurons that affect the axial muscles while the posterior horn receives information regarding touch and sensation...

 and dorsal horn of the spinal cord

Spinal cord

The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...

. Nociceptin acts at the Nociceptin receptor

Nociceptin receptor

The nociceptin receptor or NOP also known as the orphanin FQ receptor or kappa-type 3 opioid receptor is a protein that in humans is encoded by the OPRL1 gene. The nociceptin receptor is a G protein-coupled receptor whose natural ligand is known as nociceptin or orphanin FQ, a 17 amino acid...

 (NOP1), formerly known as ORL-1. The receptor is also widely distributed in the brain, including in the cortex

Cerebral cortex

The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...

, anterior olfactory nucleus

Anterior olfactory nucleus

The anterior olfactory nucleus is a portion of the forebrain of vertebrates.It is involved in olfaction.-Location:...

, lateral septum

Septal nuclei

The septal area are structures that lie below the rostrum of corpus callosum in front of lamina terminalis , composed of medium-size neurons grouped into medial, lateral, and posterior groups...

, hypothalamus

Hypothalamus

The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

, hippocampus

Hippocampus

The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

, amygdala

Amygdala

The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...

, central gray

Periaqueductal gray

Periaqueductal gray is the gray matter located around the cerebral aqueduct within the tegmentum of the midbrain. It plays a role in the descending modulation of pain and in defensive behaviour...

, pontine nuclei

Pons

The pons is a structure located on the brain stem, named after the Latin word for "bridge" or the 16th-century Italian anatomist and surgeon Costanzo Varolio . It is superior to the medulla oblongata, inferior to the midbrain, and ventral to the cerebellum. In humans and other bipeds this means it...

, interpeduncular nucleus

Interpeduncular fossa

The Interpeduncular fossa is a somewhat lozenge-shaped area of the base of the brain, limited in front by the optic chiasma, behind by the antero-superior surface of the pons, antero-laterally by the converging optic tracts, and postero-laterally by the diverging cerebral peduncles.The structures...

, substantia nigra

Substantia nigra

The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...

, raphe complex

Raphe nuclei

The raphe nuclei are a moderate-size cluster of nuclei found in the brain stem. Their main function is to release serotonin to the rest of the brain...

, locus coeruleus, and spinal cord

Spinal cord

The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...

.

The N/OFQ-NOP system is found in central and peripheral nervous tissue, where it is well placed to modulate nociception

Nociception

Nociception is defined as "the neural processes of encoding and processing noxious stimuli." It is the afferent activity produced in the peripheral and central nervous system by stimuli that have the potential to damage tissue...

. Indeed, there is some evidence that nociceptin may be involved in the phenomenon of opioid-induced hyperalgesia

Opioid-induced hyperalgesia

Opioid-induced hyperalgesia or opioid-induced abnormal pain sensitivity is a phenomenon associated with the long term use of opioids such as morphine, hydrocodone, oxycodone, and methadone. Over time, individuals taking opioids can develop an increasing sensitivity to noxious stimuli, even...

.