Nociception is the sensory nervous system's response to certain harmful or harmful stimuli. In nociception, intense chemical, mechanical, or thermal stimulation of sensory nerve cells 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 and results in a subjective experience of pain in sentient beings. Damaging mechanical and chemical stimuli are detected by nerve endings called nociceptors, which are found in the skin, on internal surfaces such as the periosteum, joint surfaces, in some internal organs; the concentration of nociceptors varies throughout the body. Some nociceptors are unspecialized free nerve endings that have their cell bodies outside the spinal column in the dorsal root ganglia. Nociceptors are categorized according to the axons which travel from the receptors to the spinal cord or brain. Nociceptors have a certain threshold. Once this threshold is reached a signal is passed along the axon of the neuron into the spinal cord.
Nociceptive threshold testing deliberately applies a noxious stimulus to a human or animal subject in order to study pain. In animals, the technique is used to study the efficacy of analgesic drugs and to establish dosing levels and period of effect. After establishing a baseline, the drug under test is given and the elevation in threshold recorded at specified time points; when the drug wears off, the threshold should return to the baseline value. In some conditions, excitation of pain fibers becomes greater as the pain stimulus continues, leading to a condition called hyperalgesia; the gate control theory of pain, proposed by Patrick David Wall and Ronald Melzack, postulates that nociception is "gated" by non-nociceptive stimuli such as vibration. Thus, rubbing a bumped knee seems to relieve pain by preventing its transmission to the brain. Pain is "gated" by signals that descend from the brain to the spinal cord to suppress incoming nociception information. Nociception can cause generalized autonomic responses before or without reaching consciousness to cause pallor, tachycardia, lightheadedness and fainting.
This overview discusses proprioception, thermoception and nociception as they are all integrally connected. Proprioception is determined by using standard mechanoreceptors. Proprioception is covered within the somatosensory system as the brain processes them together. Thermoception refers to stimuli of moderate temperatures 24–28 °C, as anything beyond that range is considered pain and moderated by nociceptors. TRP and potassium channels each respond to different temperatures which create action potentials in nerves which join the mechano system in the posterolateral tract. Thermoception, like proprioception, is covered by the somatosensory system. TRP channels that detect noxious stimuli relay that info to nociceptors that generate an action potential. Mechanical TRP channels react to depression of their cells, thermal TRP change shape in different temperatures, chemical TRP act like taste buds, signalling if their receptors bond to certain elements/chemicals. Laminae 3-5 make up nucleus proprius in spinal grey matter.
Lamina 2 makes up substantia gelatinosa of unmyelinated spinal grey matter. Substantia conveys intense, poorly localized pain. Lamina 1 project to the parabrachial area and periaqueductal grey, which begins the suppression of pain via neural and hormonal inhibition. Lamina 1 receive input from thermoreceptors via the posterolateral tract. Marginal nucleus of the spinal cord are the only unsuppressible pain signals; the parabrachial area integrates taste and pain info relays it. Parabrachial checks if the pain is being received in normal temperatures and if the gustatory system is active. Ao fibers synapse on laminae 1 and 5 while Ab synapses on 1, 3, 5, C. C fibers synapse on lamina 2; the amygdala and hippocampus encode the memory and emotion due to pain stimuli. The hypothalamus signals for the release of hormones. Periaqueductal grey hormonally signals reticular formation’s raphe nuclei to produce serotonin that inhibits laminae pain nuclei. Lateral spinothalamic tract aids in localization of pain.
Spinoreticular and spinotectal tracts are relay tracts to the thalamus that aid in the perception of pain and alertness towards it. Fibers cross over via the spinal anterior white commissure. Lateral lemniscus is the first point of integration of pain information. Inferior colliculus aids in sound orienting to pain stimuli. Superior colliculus receives IC’s input, integrates visual orienting info, uses the balance topographical map to orient the body to the pain stimuli. Inferior cerebellar peduncle integrates proprioceptive info and outputs to the vestibulocerebellum; the peduncle is not part of the lateral-spinothalamic-tract-pathway.
Operant conditioning is a learning process through which the strength of a behavior is modified by reinforcement or punishment. It is a procedure, used to bring about such learning. Although operant and classical conditioning both involve behaviors controlled by environmental stimuli, they differ in nature. In operant conditioning, stimuli present when a behavior is rewarded or punished come to control that behavior. For example, a child may learn to open a box to get the sweets inside, or learn to avoid touching a hot stove. Operant behavior is said to be "voluntary": for example, the child may face a choice between opening the box and petting a puppy. In contrast, classical conditioning involves involuntary behavior based on the pairing of stimuli with biologically significant events. For example, sight of sweets may cause a child to salivate, or the sound of a door slam may signal an angry parent, causing a child to tremble. Salivation and trembling are not operants; the study of animal learning in the 20th century was dominated by the analysis of these two sorts of learning, they are still at the core of behavior analysis.
Operant conditioning, sometimes called instrumental learning, was first extensively studied by Edward L. Thorndike, who observed the behavior of cats trying to escape from home-made puzzle boxes. A cat could escape from the box by a simple response such as pulling a cord or pushing a pole, but when first constrained, the cats took a long time to get out. With repeated trials ineffective responses occurred less and successful responses occurred more so the cats escaped more and more quickly. Thorndike generalized this finding in his law of effect, which states that behaviors followed by satisfying consequences tend to be repeated and those that produce unpleasant consequences are less to be repeated. In short, some consequences strengthen some consequences weaken behavior. By plotting escape time against trial number Thorndike produced the first known animal learning curves through this procedure. Humans appear to learn many simple behaviors through the sort of process studied by Thorndike, now called operant conditioning.
That is, responses are retained when they lead to a successful outcome and discarded when they do not, or when they produce aversive effects. This happens without being planned by any "teacher", but operant conditioning has been used by parents in teaching their children for thousands of years. B. F. Skinner is referred to as the father of operant conditioning, his work is cited in connection with this topic, his 1938 book "The Behavior of Organisms: An Experimental Analysis", initiated his lifelong study of operant conditioning and its application to human and animal behavior. Following the ideas of Ernst Mach, Skinner rejected Thorndike's reference to unobservable mental states such as satisfaction, building his analysis on observable behavior and its observable consequences. Skinner believed that classical conditioning was too simplistic to be used to describe something as complex as human behavior. Operant conditioning, in his opinion, better described human behavior as it examined causes and effects of intentional behavior.
To implement his empirical approach, Skinner invented the operant conditioning chamber, or "Skinner Box", in which subjects such as pigeons and rats were isolated and could be exposed to controlled stimuli. Unlike Thorndike's puzzle box, this arrangement allowed the subject to make one or two simple, repeatable responses, the rate of such responses became Skinner's primary behavioral measure. Another invention, the cumulative recorder, produced a graphical record from which these response rates could be estimated; these records were the primary data that Skinner and his colleagues used to explore the effects on response rate of various reinforcement schedules. A reinforcement schedule may be defined as "any procedure that delivers reinforcement to an organism according to some well-defined rule"; the effects of schedules became, in turn, the basic findings from which Skinner developed his account of operant conditioning. He drew on many less formal observations of human and animal behavior. Many of Skinner's writings are devoted to the application of operant conditioning to human behavior.
In 1948 he published Walden Two, a fictional account of a peaceful, productive community organized around his conditioning principles. In 1957, Skinner published Verbal Behavior, which extended the principles of operant conditioning to language, a form of human behavior, analyzed quite differently by linguists and others. Skinner defined new functional relationships such as "mands" and "tacts" to capture some essentials of language, but he introduced no new principles, treating verbal behavior like any other behavior controlled by its consequences, which included the reactions of the speaker's audience. Operant behavior is said to be "emitted", thus one may ask. The answer to this question is like Darwin's answer to the question of the origin of a "new" bodily structure, namely and selection; the behavior of an individual varies from moment to moment, in such aspects as the specific motions involved, the amount of force applied, or the timing of the response. Variations that lead to reinforcement are strengthened, if reinforcement is consistent, the behavior tends to remain stable.
However, behavioral variability can itself be altered through the manipulation
Transcutaneous electrical nerve stimulation
Transcutaneous electrical nerve stimulation is the use of electric current produced by a device to stimulate the nerves for therapeutic purposes. TENS, by definition, covers the complete range of transcutaneously applied currents used for nerve excitation although the term is used with a more restrictive intent, namely to describe the kind of pulses produced by portable stimulators used to treat pain; the unit is connected to the skin using two or more electrodes. A typical battery-operated TENS unit is able to modulate pulse width and intensity. TENS is applied at high frequency with an intensity below motor contraction or low frequency with an intensity that produces motor contraction. While the use of TENS has proved effective in clinical studies, there is controversy over which conditions the device should be used to treat. TENS devices available to the domestic market are used as a non-invasive nerve stimulation intended to reduce both acute and chronic pain. One review from 2007 felt that the evidence supports a benefit in chronic musculoskeletal pain Results from a task force on neck pain in 2008 found no clinically significant benefit to TENS for the treatment of neck pain when compared to a placebo treatment.
A 2010 review did not find evidence to support the use of TENS for chronic low back pain. There is tentative evidence; as of 2015, the efficacy of TENS therapy for phantom limb pain is not known as no randomized controlled trials have been performed. In principle, an adequate intensity of stimulation is necessary to achieve pain relief with TENS. An analysis of treatment fidelity showed that higher fidelity trials tended to have a positive outcome. A few studies have shown objective evidence that TENS may modulate or suppress pain signals in the brain. One used evoked cortical potentials to show that electric stimulation of peripheral A-beta sensory fibers reliably suppressed A-delta fiber nociceptive processing. Two other studies used functional magnetic resonance imaging: one showed that high-frequency TENS produced a decrease in pain-related cortical activations in patients with carpal tunnel syndrome, while the other showed that low-frequency TENS decreased shoulder impingement pain and modulated pain-induced activation in the brain.
A head-mounted TENS device called Cefaly was approved by the United States Food and Drug Administration, on March 11, 2014, for the prevention of migraines. The Cefaly device was found effective in preventing migraine attacks in a randomized sham-controlled trial; this was the first TENS device. A study performed on healthy human subjects demonstrates that repeated application of TENS can create analgesic tolerance and reduce its efficacy. Studies have stated that TENS "has been shown not to be effective in postoperative and labour pain." TENS has been extensively used in non-odontogenic orofacial pain relief. In addition, TENS and ultra low frequency-TENS are employed in diagnosis and treatment of temporomandibular joint dysfunction. Further clinical studies are required to determine its efficacy. Electrical stimulation for pain control was used in ancient Rome, 63 A. D, it was reported by Scribonius Largus that pain was relieved by standing on an electrical fish at the seashore. In the 16th through the 18th century various electrostatic devices were used for headache and other pains.
Benjamin Franklin was a proponent of this method for pain relief. In the 19th century a device called the electreat, along with numerous other devices were used for pain control and cancer cures. Only the electreat survived into the 20th century, but was not portable, had limited control of the stimulus. Development of modern TENS unit is credited to C. Norman Shealy; the first modern, patient-wearable TENS was patented in the United States in 1974. It was used for testing the tolerance of chronic pain patients to electrical stimulation before implantation of electrodes in the spinal cord dorsal column; the electrodes were attached to an implanted receiver, which received its power from an antenna worn on the surface of the skin. Although intended only for testing tolerance to electrical stimulation, many of the patients said they received so much relief from the TENS itself that they never returned for the implant. A number of companies began manufacturing TENS units after the commercial success of the Medtronic device became known.
The neurological division of Medtronic, founded by Don Maurer, Ed Schuck and Charles Ray, developed a number of applications for implanted electrical stimulation devices for treatment of epilepsy, Parkinson's disease, other disorders of the nervous system. Today many people confuse TENS with electrical muscle stimulation. EMS and TENS devices look similar, with both using long electric lead electrodes. TENS is for blocking pain; as reported, TENS has different effects on the brain. A recent RCT shown that sensory ULF-TENS applied on the skin proximally to trigeminal nerve, reduced the effect of acute mental stress assessed by heart rate variability. There are several anatomical locations where TENS electrodes are contraindicated: Over the eyes due to the risk of increasing intraocular pressure Transcerebrally On the front of the neck due to the risk of an acute hypotension or a laryngospasm Through the chest using an anterior and posterior electrode positions, or other transthoracic appli
Stress, either physiological or biological, is an organism's response to a stressor such as an environmental condition. Stress is the body's method of reacting to a condition such as a threat, challenge or physical and psychological barrier. Stimuli that alter an organism's environment are responded to by multiple systems in the body; the autonomic nervous system and hypothalamic-pituitary-adrenal axis are two major systems that respond to stress. The sympathoadrenal medullary axis may activate the fight-or-flight response through the sympathetic nervous system, which dedicates energy to more relevant bodily systems to acute adaptation to stress, while the parasympathetic nervous system returns the body to homeostasis; the second major physiological stress, the HPA axis regulates the release of cortisol, which influences many bodily functions such as metabolic and immunological functions. The SAM and HPA axes are regulated by several brain regions, including the limbic system, prefrontal cortex, amygdala and stria terminalis.
Through these mechanisms, stress can alter memory functions, immune function and susceptibility to diseases. Definitions of stress differ. One system suggests there are five types of stress labeled "acute time-limited stressors", "brief naturalistic stressors", "stressful event sequences", "chronic stressors", "distant stressors". An acute time-limited stressor involves a short-term challenge, while a brief natural stressor involves an event, normal but challenging. A stressful event sequence is a stressor that occurs, continues to yield stress into the immediate future. A chronic stressor involves exposure to a long-term stressor, a distant stressor is a stressor, not immediate. Stress and illness may have intersecting components. Several studies indicate such a link, while theories of the stress–illness link suggest that both acute and chronic stress can cause illness, lead to changes in behavior and in physiology. Behavioral changes can include smoking, changes in eating habits and physical activity.
Physiological changes can include changes in sympathetic activation or HPA activity, immunological function. However, there is much variability in the link between illness; the HPA axis regulates many bodily functions, both behavioral and physiological, through the release of glucocorticoid hormones. The HPA axis activity varies with a spike in the morning; the axis involves the release of corticotropin releasing hormone and vasopressin from the hypothalamus which stimulates the pituitary to secrete ACTH. ACTH may stimulate the adrenal glands to secrete cortisol; the HPA axis is subject to negative feedback regulation as well. The release of CRH and VP are regulated by descending glutaminergic and GABAergic pathways from the amygdala, as well as noradrenergic projections. Increased cortisol acts to increase blood glucose, blood pressure, surpasses lysosomal, immunological activity. Under other circumstances the activity may differ. Increased cortisol favors habit based learning, by favoring memory consolidation of emotional memories.
Selye demonstrated that stress decreases adaptability of an organism and proposed to describe the adaptability as a special resource, adaptation energy. One study considered adaptation energy as an internal coordinate on the "dominant path" in the model of adaptation. Stress can make the individual more susceptible to physical illnesses like the common cold. Stressful events, such as job changes, may result in insomnia, impaired sleeping, physical and psychological health complaints. Research indicates the type of stressor and individual characteristics such as age and physical well-being before the onset of the stressor can combine to determine the effect of stress on an individual. An individual's personality characteristics and childhood experiences with major stressors and traumas may dictate their response to stressors. Chronic stress and a lack of coping resources available or used by an individual can lead to the development of psychological issues such as delusions and anxiety; this is true regarding chronic stressors.
These are stressors that may not be as intense as an acute stressor like a natural disaster or a major accident, but they persist over longer periods of time. These types of stressors tend to have a more negative effect on health because they are sustained and thus require the body's physiological response to occur daily; this depletes the body's energy more and occurs over long periods of time when these microstressors cannot be avoided. See allostatic load for further discussion of the biological process by which chronic stress may affect the body. For example, studies have found that caregivers those of dementia patients, have higher levels of depression and worse physical health than non-caregivers; when humans are under chronic stress, permanent changes in their physiological and behavioral responses may occur. Chronic stress can include events such as caring for a spouse with dementia, or may result from brief focal events that have long term effects, such as experiencing a sexual assault.
Studies have shown that psychological stress may directly contribute to the disproportionately high rates of coronary heart disease morbidity and mortality and its etiologic risk factors. Acute and chronic stress have been shown to raise serum lipids and are associated with clinical coronary events. However, it is possible for individuals to exhibit hardiness—a term
The respiratory system is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies depending on the size of the organism, the environment in which it lives and its evolutionary history. In land animals the respiratory surface is internalized as linings of the lungs. Gas exchange in the lungs occurs in millions of small air sacs called alveoli in mammals and reptiles, but atria in birds; these microscopic air sacs have a rich blood supply, thus bringing the air into close contact with the blood. These air sacs communicate with the external environment via a system of airways, or hollow tubes, of which the largest is the trachea, which branches in the middle of the chest into the two main bronchi; these enter the lungs where they branch into progressively narrower secondary and tertiary bronchi that branch into numerous smaller tubes, the bronchioles. In birds the bronchioles are termed parabronchi.
It is the bronchioles, or parabronchi that open into the microscopic alveoli in mammals and atria in birds. Air has to be pumped from the environment into the alveoli or atria by the process of breathing which involves the muscles of respiration. In most fish, a number of other aquatic animals the respiratory system consists of gills, which are either or external organs, bathed in the watery environment; this water flows over the gills by a variety of passive means. Gas exchange takes place in the gills which consist of thin or flat filaments and lammelae which expose a large surface area of vascularized tissue to the water. Other animals, such as insects, have respiratory systems with simple anatomical features, in amphibians the skin plays a vital role in gas exchange. Plants have respiratory systems but the directionality of gas exchange can be opposite to that in animals; the respiratory system in plants includes anatomical features such as stomata, that are found in various parts of the plant.
In humans and other mammals, the anatomy of a typical respiratory system is the respiratory tract. The tract is divided into a lower respiratory tract; the upper tract includes the nose, nasal cavities, sinuses and the part of the larynx above the vocal folds. The lower tract includes the lower part of the larynx, the trachea, bronchi and the alveoli; the branching airways of the lower tract are described as the respiratory tree or tracheobronchial tree. The intervals between successive branch points along the various branches of "tree" are referred to as branching "generations", of which there are, in the adult human about 23; the earlier generations, consisting of the trachea and the bronchi, as well as the larger bronchioles which act as air conduits, bringing air to the respiratory bronchioles, alveolar ducts and alveoli, where gas exchange takes place. Bronchioles are defined as the small airways lacking any cartilagenous support; the first bronchi to branch from the trachea are the right and left main bronchi.
Second only in diameter to the trachea, these bronchi enter the lungs at each hilum, where they branch into narrower secondary bronchi known as lobar bronchi, these branch into narrower tertiary bronchi known as segmental bronchi. Further divisions of the segmental bronchi are known as 4th order, 5th order, 6th order segmental bronchi, or grouped together as subsegmental bronchi. Compared to the, on average, 23 number of branchings of the respiratory tree in the adult human, the mouse has only about 13 such branchings; the alveoli are the dead end terminals of the "tree", meaning that any air that enters them has to exit via the same route. A system such as this creates dead space, a volume of air that fills the airways after exhalation and is breathed back into the alveoli before environmental air reaches them. At the end of inhalation the airways are filled with environmental air, exhaled without coming in contact with the gas exchanger; the lungs contract during the breathing cycle, drawing air in and out of the lungs.
The volume of air moved in or out of the lungs under normal resting circumstances, volumes moved during maximally forced inhalation and maximally forced exhalation are measured in humans by spirometry. A typical adult human spirogram with the names given to the various excursions in volume the lungs can undergo is illustrated below: Not all the air in the lungs can be expelled during maximally forced exhalation; this is the residual volume of about 1.0-1.5 liters. Volumes that include the residual volume can therefore not be measured by spirometry, their measurement requires special techniques. The rates at which air is breathed in or out, either through the mouth or nose, or into or out of the alveoli are tabulated below, together with how they are calculated; the number of breath cycles per minute is known as the respiratory rate. In mammals, inhalation at rest is due to the contraction of the diaphragm; this is an upwardly domed sheet of muscle that separates the thoracic cavity from the abdominal cavity.
When it contracts the sheet flattens. The contracting diaphragm pushes, but because the pelvic floo