In physiology, nociception, also nocioception; from Latin nocere 'to harm/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 to trigger an appropriate defensive response.
The brainstem is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is continuous with the thalamus of the diencephalon through the tentorial notch, and sometimes the diencephalon is included in the brainstem.
The midbrain or mesencephalon is the uppermost portion of the brainstem connecting the diencephalon and cerebrum with the pons. It consists of the cerebral peduncles, tegmentum, and tectum.
The raphe nuclei are a moderate-size cluster of nuclei found in the brain stem. They have 5-HT1 receptors which are coupled with Gi/Go-protein-inhibiting adenyl cyclase. They function as autoreceptors in the brain and decrease the release of serotonin. The anxiolytic drug Buspirone acts as partial agonist against these receptors. Selective serotonin reuptake inhibitor (SSRI) antidepressants are believed to act in these nuclei, as well as at their targets.
A nociceptor is a sensory neuron that responds to damaging or potentially damaging stimuli by sending "possible threat" signals to the spinal cord and the brain. The brain creates the sensation of pain to direct attention to the body part, so the threat can be mitigated; this process is called nociception.
The spinothalamic tract is a nerve tract in the anterolateral system in the spinal cord. This tract is an ascending sensory pathway to the thalamus. From the ventral posterolateral nucleus in the thalamus, sensory information is relayed upward to the somatosensory cortex of the postcentral gyrus.
Dopaminergic pathways in the human brain are involved in both physiological and behavioral processes including movement, cognition, executive functions, reward, motivation, and neuroendocrine control. Each pathway is a set of projection neurons, consisting of individual dopaminergic neurons.
The ventral tegmental area (VTA), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is the origin of the dopaminergic cell bodies of the mesocorticolimbic dopamine system and other dopamine pathways; it is widely implicated in the drug and natural reward circuitry of the brain. The VTA plays an important role in a number of processes, including reward cognition and orgasm, among others, as well as several psychiatric disorders. Neurons in the VTA project to numerous areas of the brain, ranging from the prefrontal cortex to the caudal brainstem and several regions in between.
β-Endorphin (beta-endorphin) is an endogenous opioid neuropeptide and peptide hormone that is produced in certain neurons within the central nervous system and peripheral nervous system. It is one of three endorphins that are produced in humans, the others of which include α-endorphin and γ-endorphin.
The reticular formation is a set of interconnected nuclei in the brainstem that spans from the lower end of the medulla oblongata to the upper end of the midbrain. The neurons of the reticular formation make up a complex set of neural networks in the core of the brainstem. The reticular formation is made up of a diffuse net-like formation of reticular nuclei which is not well-defined. It may be seen as being made up of all the interspersed cells in the brainstem between the more compact and named structures.
Some philosophers, such as Jeremy Bentham, Baruch Spinoza, and Descartes, have hypothesized that the feelings of pain and pleasure are part of a continuum.
The zona incerta (ZI) is a horizontally elongated small nucleus that separates the larger subthalamic nucleus from the thalamus. Its connections project extensively over the brain from the cerebral cortex down into the spinal cord.
The nucleus raphe magnus (NRM) is one of the seven raphe nuclei. It is situated in the pons in the brainstem, just rostral to the nucleus raphe obscurus.
The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA), contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cognitive and physical processes, such as promoting feeding behavior and arousal, reducing pain perception, and regulating body temperature, digestive functions, and blood pressure, among many others. Clinically significant disorders that involve dysfunctions of the orexinergic projection system include narcolepsy, motility disorders or functional gastrointestinal disorders involving visceral hypersensitivity, and eating disorders.
The ventrobasal complex (VB) is a relay nucleus of the thalamus for nociceptive stimuli received from nociceptive nerves. The VB consists of the ventral posteromedial nucleus (VPM) and the ventral posterolateral nucleus (VPL). In some species, the ventral posterolateral nucleus, pars caudalis is also a part of the VB. The VB gets inputs from the spinothalamic tract, medial lemniscus, and corticothalamic tract. The main output of the VB is the primary somatosensory cortex.
Cannabinoid receptor 1 (CB1), is a G protein-coupled cannabinoid receptor that in humans is encoded by the CNR1 gene. The human CB1 receptor is expressed in the peripheral nervous system and central nervous system. It is activated by endogenous cannabinoids called endocannabinoids, a group of retrograde neurotransmitters that include lipids, such as anandamide and 2-arachidonoylglycerol (2-AG); plant phytocannabinoids, such as docosatetraenoylethanolamide found in wild daga, the compound THC which is an active constituent of the psychoactive drug cannabis; and synthetic analogs of THC. CB1 is antagonized by the phytocannabinoid tetrahydrocannabivarin (THCV).
Sleep onset is the transition from wakefulness into sleep. Sleep onset usually transits into non-rapid eye movement sleep but under certain circumstances it is possible to transit from wakefulness directly into rapid eye movement sleep.
The rostral ventromedial medulla (RVM), or ventromedial nucleus of the spinal cord, is a group of neurons located close to the midline on the floor of the medulla oblongata. The rostral ventromedial medulla sends descending inhibitory and excitatory fibers to the dorsal horn spinal cord neurons. There are 3 categories of neurons in the RVM: on-cells, off-cells, and neutral cells. They are characterized by their response to nociceptive input. Off-cells show a transitory decrease in firing rate right before a nociceptive reflex, and are theorized to be inhibitory. Activation of off-cells, either by morphine or by any other means, results in antinociception. On-cells show a burst of activity immediately preceding nociceptive input, and are theorized to be contributing to the excitatory drive. Neutral cells show no response to nociceptive input.
The rostromedial tegmental nucleus (RMTg), also known as the tail of the ventral tegmental area (tVTA), is a GABAergic nucleus which functions as a "master brake" for the midbrain dopamine system. This region was discovered by the researchers, M. Barrot, J.Kaufling and T. Jhou. It is poorly differentiated from the rest of the ventral tegmental area (VTA) and possesses robust functional and structural links to the dopamine pathways. Notably, both acute and chronic exposure to psychostimulants have been shown to induce FosB and ΔFosB expression in the RMTg; no other drug type has been shown to induce these proteins in the RMTg.
