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Nociceptin Receptor Antagonists
Nociceptin/orphanin FQ (N/OFQ), a 17-amino acid neuropeptide, is the endogenous ligand for the nociceptin receptor (NOP, ORL-1). Nociceptin acts as a potent anti-analgesic, effectively counteracting the effect of pain-relievers; it's activation is associated with brain functions such as pain sensation and fear learning. The gene coding for prepronociceptin is located on Ch8p21 in humans. Nociceptin is derived from the prepronociceptin protein, as are a further two peptides, nocistatin and NocII, both of which inhibit N/OFQ receptor function. Nociceptin is the first example of reverse pharmacology; the NOP receptor was discovered before the endogenous ligand which was discovered by two separate groups in 1995. Roles of nociceptin Since its discovery, nociceptin has been of great interest to researchers. Nociceptin is a peptide related to the opioid class of compounds (ex. morphine and codeine), but it does not act at the classic opioid receptors (namely, mu, kappa, and delta o ...
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Amino Acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha amino acids appear in the genetic code. Amino acids can be classified according to the locations of the core structural functional groups, as Alpha and beta carbon, alpha- , beta- , gamma- or delta- amino acids; other categories relate to Chemical polarity, polarity, ionization, and side chain group type (aliphatic, Open-chain compound, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid '' residues'' form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling life ...
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Cerebral Cortex
The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of allocortex. It is separated into two cortices, by the longitudinal fissure that divides the cerebrum into the left and right cerebral hemispheres. The two hemispheres are joined beneath the cortex by the corpus callosum. The cerebral cortex is the largest site of neural integration in the central nervous system. It plays a key role in attention, perception, awareness, thought, memory, language, and consciousness. The cerebral cortex is part of the brain responsible for cognition. In most mammals, apart from small mammals that have small brains, the cerebral cortex is folded, providing a greater surface area in the confined volume of the cranium. Apart from minimising brain and cranial volume, cortical folding is crucial for the brain ...
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Central Nervous System
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all parts of the bodies of bilaterally symmetric and triploblastic animals—that is, all multicellular animals except sponges and diploblasts. It is a structure composed of nervous tissue positioned along the rostral (nose end) to caudal (tail end) axis of the body and may have an enlarged section at the rostral end which is a brain. Only arthropods, cephalopods and vertebrates have a true brain (precursor structures exist in onychophorans, gastropods and lancelets). The rest of this article exclusively discusses the vertebrate central nervous system, which is radically distinct from all other animals. Overview In vertebrates, the brain and spinal cord are both enclosed in the meninges. The meninges provide a barrier to chemicals dissolv ...
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Hyperalgesia
Hyperalgesia ( or ; 'hyper' from Greek ὑπέρ (huper, “over”), '-algesia' from Greek algos, ἄλγος (pain)) is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves and can cause hypersensitivity to stimulus. Prostaglandins E and F are largely responsible for sensitizing the nociceptors. Temporary increased sensitivity to pain also occurs as part of sickness behavior, the evolved response to infection. Types Hyperalgesia can be experienced in focal, discrete areas, or as a more diffuse, body-wide form. Conditioning studies have established that it is possible to experience a learned hyperalgesia of the latter, diffuse form. The focal form is typically associated with injury, and is divided into two subtypes: * ''Primary hyperalgesia'' describes pain sensitivity that occurs directly in the damaged tissues. * ''Secondary hyperalgesia'' describes pain sensitivity that occurs in surrounding undamaged tissues. ...
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Nociception
Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the sensory nervous system's process of encoding noxious stimuli. It deals with a series of events and processes required for an organism to receive a painful stimulus, convert it to a molecular signal, and recognize and characterize the signal in order to trigger an appropriate defense response. In nociception, intense chemical (e.g., capsaicin present in Chili pepper or Cayenne pepper), mechanical (e.g., cutting, crushing), or thermal (heat and cold) stimulation of sensory neurons called nociceptors produces a signal that travels along a chain of nerve fibers via the spinal cord to the brain. Nociception triggers a variety of physiological and behavioral responses to protect the organism against an aggression and usually results in a subjective experience, or perception, of pain in sentient beings. Detection of noxious stimuli Potentially damaging mechanical, thermal, and chemical stimuli are detected ...
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Locus Coeruleus
The locus coeruleus () (LC), also spelled locus caeruleus or locus ceruleus, is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system. The locus coeruleus, which in Latin means "blue spot", is the principal site for brain synthesis of norepinephrine (noradrenaline). The locus coeruleus and the areas of the body affected by the norepinephrine it produces are described collectively as the locus coeruleus-noradrenergic system or LC-NA system. Norepinephrine may also be released directly into the blood from the adrenal medulla. Anatomy The locus coeruleus (LC) is located in the posterior area of the rostral pons in the lateral floor of the fourth ventricle. It is composed of mostly medium-size neurons. Melanin granules inside the neurons of the LC contribute to its blue colour. Thus, it is also known as the nucleus pigmentosus pontis, meaning "heavily pigmented nucleus of the pons." The n ...
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Substantia Nigra
The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although the substantia nigra appears as a continuous band in brain sections, anatomical studies have found that it actually consists of two parts with very different connections and functions: the pars compacta (SNpc) and the pars reticulata (SNpr). The pars compacta serves mainly as a projection to the basal ganglia circuit, supplying the striatum with dopamine. The pars reticulata conveys signals from the basal ganglia to numerous other brain structures. Structure The substantia nigra, along with four other nuclei, is part ...
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Interpeduncular Fossa
The interpeduncular fossa is a deep depression of the ventral surface of the midbrain between the two crura cerebri. It has been found in humans and macaques, but not in rats or mice, showing that this is a relatively new evolutionary region. Anatomy The interpeduncular fossa is a somewhat rhomboid-shaped area of the base of the brain. Features The lateral wall of the interpeduncular fossa bears a groove - the oculomotor sulcus - from which rootlets of the oculomotor nerve emerge from the substance of the brainstem and aggregate into a single fascicle. Anatomical relations The ventral tegmental area lies at the depth of the interpeduncular fossa. Boundaries The interpeduncular fossa is 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 floor of interpeduncular fossa, from behind forward, are the posterior perforated substance, ...
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Pons
The pons (from Latin , "bridge") is part of the brainstem that in humans and other bipeds lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum. The pons is also called the pons Varolii ("bridge of Varolius"), after the Italian anatomist and surgeon Costanzo Varolio (1543–75). This region of the brainstem includes neural pathways and tracts that conduct signals from the brain down to the cerebellum and medulla, and tracts that carry the sensory signals up into the thalamus.Saladin Kenneth S.(2007) Anatomy & physiology the unity of form and function. Dubuque, IA: McGraw-Hill Structure The pons is in the brainstem situated between the midbrain and the medulla oblongata, and in front of the cerebellum. A separating groove between the pons and the medulla is the inferior pontine sulcus. The superior pontine sulcus separates the pons from the midbrain. The pons can be broadly divided into two parts: the basilar part of the pons (ventral ...
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Periaqueductal Gray
The periaqueductal gray (PAG, also known as the central gray) is a brain region that plays a critical role in autonomic function, motivated behavior and behavioural responses to threatening stimuli. PAG is also the primary control center for descending pain modulation. It has enkephalin-producing cells that suppress pain. The periaqueductal gray is the gray matter located around the cerebral aqueduct within the tegmentum of the midbrain. It projects to the nucleus raphe magnus, and also contains descending autonomic tracts. The ascending pain and temperature fibers of the spinothalamic tract send information to the PAG via the spinomesencephalic tract (so-named because the fibers originate in the spine and terminate in the PAG, in the mesencephalon or midbrain). This region has been used as the target for brain-stimulating implants in patients with chronic pain. Role in analgesia Stimulation of the periaqueductal gray matter of the midbrain activates enkephalin-releasing ne ...
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Amygdala
The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex vertebrates, including humans. Shown to perform a primary role in the processing of memory, decision making, and emotional responses (including fear, anxiety, and aggression), the amygdalae are considered part of the limbic system. The term "amygdala" was first introduced by Karl Friedrich Burdach in 1822. Structure The regions described as amygdala nuclei encompass several structures of the cerebrum with distinct connectional and functional characteristics in humans and other animals. Among these nuclei are the basolateral complex, the cortical nucleus, the medial nucleus, the central nucleus, and the intercalated cell clusters. The basolateral complex can be further subdivided into the lateral, the basal, and the accessory basal nucle ...
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