Theories of pain
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For as long as humans have felt pain, they have devised explanations for its existence and sought soothing agents to dull or end the agony. Clay tablets dating back to 5,000 BC have been discovered that mention the cultivation and use of the opium poppy to bring joy and relieve pain. Homer, the Greek writer, described Telemachus, a man who used opium to relieve pain and forget his worries in his epic, The Odyssey, written in 800 BC.  While some cultures investigated analgesics and permitted or encouraged their use, others saw pain as a necessary, integral sensation. The pain was used by physicians in the nineteenth century as a diagnostic tool, with the theory that a more significant amount of personally perceived pain was correlated to greater internal vitality, and as a treatment in and of itself, inflicting pain on their patients to rid the patient of evil and unbalanced humor.  This article focuses on how pain has been perceived throughout time and culture and how malleable an individual’s perception of pain can be due to factors such as situation, visual perception of the pain, and previous experience with pain.
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Theories from the beginning
Because of the relatively recent discovery of neurons and how they conduct and interpret signals, including sensations like pain, within the body, various theories about the causes of pain and its role or function have been proposed. Even within seemingly small groups, such as the ancient Greeks, competing theories about the root cause of pain existed. When enumerating the five senses, Aristotle did not include a sense of pain; he, like Plato before him, saw pain and pleasure as emotions rather than sensations (“passions of the soul”).  On the other hand, Hippocrates believed that pain was caused by an imbalance in a person’s vital fluids. Aristotle did not believe that the brain played any role in pain processing then and instead identified the heart as the central organ for pain sensation.  He was the primary proponent of the cardio-centric theory of the soul, which contrasted with the encephalo-centric proposals of, among others, Hippocrate, who explicitly considered the brain to be the source of “our pains, grief, anxieties, and tears” (Hippocrates, in W.H.S. Jones (Ed. ), The Sacred Disease, vol. 2, The Loeb Classical Library, Cambridge, 1923). The debate between encephalocentrists and cardio centrists lasted well into the Renaissance, with the Aristotelic cardio-centric vision dominating among philosophers despite being challenged by eminent doctors like Galen (Crivellato E, Ribatti D. Soul, mind, brain: Greek philosophy and the birth of neuroscience. Brain Research Bulletin 71 (2007) 327-336).
Early Modern Period and the Middle Ages
Avicenna proposed in the 11th century that there were several feeling senses, including touch, pain, and titillation.
René Descartes’ portrait
Pain may be viewed as a punishment or a test from God in a religious context. However, this religious perspective did not prevent Early Modern Physicians from being concerned about the problem of pain: they attempted to cure it with pain-killers known as “anodynes,” discussed the problem of phantom pain, described in the 16th century by surgeon Ambroise Paré, and proposed detailed descriptions of the signs of pain. 
René Descartes proposed in his Treatise of Man (published posthumously, 1664) that the body was more like a machine and that pain was a disturbance that traveled down nerve fibers until it reached the brain.
 This theory changed pain perception from a spiritual experience to a physical, mechanical sensation, implying that a cure could be discovered by researching and locating pain fibers within the body.
The theory of specificity
Descartes’ pain pathway: “Particles of heat” (A) activate a patch of skin (B) connected by a fine thread (cc) to a valve in the brain (de), where this activity opens the valve, allowing animal spirits to flow from a cavity (F) into the muscles, causing them to flinch from the stimulus, turn the head and eyes toward the affected body part, and move the hand and turn the body protectively.
 The specificity theory states that pain is “a specific sensation with its sensory apparatus independent of touch and other senses”, emerged in the nineteenth century but was foreshadowed by Avicenna and Descartes’ work.
In 1811, Scottish anatomist Charles Bell proposed that different sensory receptors are adapted to respond to only one type of stimulus.
 After establishing that a single stimulus type (e.g., a blow, an electric current) can produce different sensations depending on the type of nerve stimulated, Johannes Müller hypothesized in 1839 that there is a specific energy unique to each of the five nerve types that serve Aristotle’s five senses and that the type of energy determines the type of sensation each nerve produces.  He considered itching, pleasure, pain, heat, cold, and touch variations of the single sense he referred to as “feeling and touch.”  Müller’s doctrine ended the ancient belief that nerves carried actual properties or incorporeal copies of the perceived object, ushering in the modern era of sensory psychology and prompting others to ask, do the nerves evoke the various qualities of touch and feel have specific characteristics? 
In 1831, Filippo Pacini isolated receptors in the nervous system that detect pressure and vibrations. In 1852, Georg Meissner and Rudolf Wagner described receptors sensitive to light touch, and Wilhelm Krause discovered a receptor sensitive to gentle vibration in 1860.  In 1858, Moritz Schiff established the specificity theory of pain by demonstrating that touch and pain sensations traveled to the brain via separate spinal cord pathways.  Magnus Blix reported in 1882 that when specific spots on the skin are stimulated, they elicit sensations of either cold or heat, and proposed that “the different sensations of cool and warm are caused by stimulation of different, specific receptors in the skin.”  Max von Frey discovered and described these heat and cold receptors, and in 1896, he reported finding “pain spots” on human subjects’ skin.  Von Frey proposed that there are low-threshold cutaneous spots that elicit touch and high-threshold cutaneous spots that elicit pain and that pain is a distinct cutaneous sensation that is independent of touch, heat, and cold and is associated with free nerve endings. 
Intensive theoretical study
Erasmus Darwin supported the idea advanced in Plato’s Timaeus in the first volume of his 1794 Zoonomia, or the Laws of Organic Life, that pain is an emotional state produced by more robust than normal stimuli such as intense light, pressure, or temperature.
 In 1874, Wilhelm Erb argued that pain could be caused by any sensory stimulus that is intense enough, and his formulation of the hypothesis became known as the intensive theory. 
Alfred Goldscheider (1884) demonstrated the existence of specific heat and cold sensors by inducing heat and cold sensations by penetrating and electrically stimulating different nerve trunks while bypassing their receptors. Despite his failure to find specific pain-sensitive spots on the skin, Goldscheider concluded in 1895 that the available evidence supported pain specificity, a position he held until a series of experiments by Bernhard Naunyn in 1889.  Naunyn prodded the skin of tabes dorsalis patients at a rate of 60-600 times per second, below their touch threshold (e.g., with a hair), causing unbearable pain in 6-20 seconds. He obtained similar results when using other stimuli, such as electricity, to produce rapid, sub-threshold stimulation, and concluded that pain is the result of summation. In 1894, Goldscheider extended the intensive theory, proposing that each tactile nerve fiber can elicit three distinct qualities of sensation – tickle, touch, and pain – the quality depending on the intensity of stimulation; and extended Naunyn’s summation idea, proposing that, over time, activity from peripheral fibers may accumulate in the dorsal horn of the spinal cord and “spill over” to a pain-signaling spinal cord fiber once a threshold of   In his 1896 textbook, British psychologist Edward Titchener stated, “excessive stimulation of any sense organ or direct injury to any sensory nerve occasioned the common sensation of pain.” 
Theories at odds
By the mid-1890s, physiologists (particularly von Frey) and clinicians backed specificity, while psychologists backed the intensive theory. However, following the publication of a series of clinical observations by Henry Head in England between 1893 and 1896, and von Frey’s experiments between 1894 and 1897, psychologists migrated to specificity almost en masse. By the end of the century, most physiology and psychology textbooks presented pain specificity as fact, with Titchener in 1898 now placing “the sensation of pain” alongside that of pressure, heat, and cold. Though Goldscheider’s elaboration of intensive theory was no longer prominent in textbooks, it stood its ground in opposition to von Frey’s specificity at the research frontiers. It was supported by some influential theorists well into the mid-twentieth century.  
In 1943, William Kenneth Livingston proposed a summation theory, claiming that high-intensity signals arriving at the spinal cord from nerve or tissue damage set up a reverberating, self-exciting loop of activity in a pool of interneurons and that once a threshold of activity is crossed, these interneurons activate “transmission” cells, which carry the signal to the brain’s pain mechanism; and that the reverberating interneuron activity spreads to other spinal RW Gerard made a similar proposal in 1951, claiming that intense peripheral nerve signaling could cause a temporary failure of inhibition in spinal cord neurons, allowing them to fire as synchronized pools with signal volleys strong enough to activate the pain mechanism. 
Building on John Paul Nafe’s 1934 suggestion that different cutaneous qualities result from different temporal and spatial stimulation patterns, DC Sinclair and G Weddell’s 1955 “peripheral pattern theory” proposed that all skin fiber endings (except for those innervating hair cells) are identical. That pain is produced by intense stimulation of these fibers.
 Willem Noordenbos discovered in 1953 that a signal carried from the site of injury along large diameter “touch, pressure, or vibration” fibers can inhibit the signal carried by thinner “pain” fibers, with the ratio of significant fiber signal to thin fiber signal determining pain intensity; thus, we rub a smack. This was interpreted as evidence that the stimulation pattern (in this case, of large and thin fibers) modulates pain intensity. 
Theory of gate control
The theory of gate control is the main topic of this article.
Ronald Melzack and Patrick Wall published their “gate control” pain theory in the Science article “Pain Mechanisms: A New Theory” in 1965.
 The authors proposed that both thin (pain) and large diameter (touch, pressure, vibration) nerve fibers carry information from the site of injury to two destinations in the dorsal horn of the spinal cord: transmission cells, which carry the pain signal up to the brain, and inhibitory interneurons, which block transmission cell activity. Transmission cells are activated by activity in both thin and large-diameter fibers. Thin fiber activity inhibits inhibitory cells (allowing the transmission cell to fire), whereas considerable diameter fiber activity excites inhibitory cells (tending to inhibit transmission cell activity). As a result, the greater the ratio of large fiber (touch, pressure, vibration) activity to thin fiber activity at the inhibitory cell, the less pain is felt. The authors created a neural “circuit diagram” to explain why we smack each other.  They imagined not only a signal traveling from the site of injury to the inhibitory and transmission cells and then up the spinal cord to the brain but also a signal traveling directly up the cord to the brain (bypassing the inhibitory and transmission cells) and then triggering a signal back down the spinal cord to modulate inhibitory cell activity, depending on the state of the brain (and so pain intensity). The theory provided a physiological explanation for the previously observed psychological effect on pain perception. 
Theories of the present day
A biopsychosocial occurrence
The International Association for the Study of Pain sought a consensus definition of pain in 1975, eventually settling on “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” as the final definition.
 This definition makes it clear that while pain is understood to be a physical phenomenon, a person’s emotional state and the context or situation associated with the pain influence the perception of the nociceptive or harmful event.
The Shoshone Indians’ Sun Dance
Modern research has gathered substantial evidence to support the theory that pain is a biopsychosocial phenomenon that encompasses culture, nociceptive stimuli, and the environment in the experience and perception of pain. The Sun Dance, for example, is a Native American ritual performed by traditional groups. Cuts are made into the chest of a young man during this ritual. Leather strips are threaded through the cuts, and poles are tied to the leather. This ritual lasts for hours and undoubtedly generates a significant amount of nociceptive signaling, but the pain may not be perceived as harmful. The ritual is centered on overcoming and transcending the effects of pain, where the pain is either welcomed or not perceived at all. 
Pain perception and visual input
Additional research has revealed that pain perception is influenced by various contextual factors, including vision. Researchers discovered that when a subject views the area of their body being stimulated, the subject reports less pain.  One study, for example, used heat stimulation on their subjects’ hands. When the subject was instructed to look at their hand during the painful heat stimulus, the subject reported an analgesic effect and a higher temperature pain threshold. Furthermore, as the view of their hand was increased, so did the analgesic effect, and vice versa. This study demonstrated how visual input influences pain perception.
The use of functional magnetic resonance imaging (fMRI) to study brain activity confirms the link between visual perception and pain perception. It has been discovered that the brain regions that convey pain perception also encode the size of visual inputs.  The magnitude-related insula of the insular cortex functions to perceive the size of visual stimulation and integrate that concept across various sensory systems, including pain perception. This area also overlaps with the nociceptive-specific insula, a section of the insula that processes nociception selectively, implying that the two areas interact and interface. This interaction informs the individual about the amount of relative pain they are experiencing, resulting in a subjective perception of pain based on the current visual stimulus.
Humans have always sought to understand why they suffer and how that occurs. The pain was once thought to be the work of evil spirits, but it is now recognized as a neurological signal. However, pain perception is not absolute and can be influenced by various factors, such as the context surrounding the painful stimulus, visual perception, and an individual’s personal pain history.
Description of the Theory of Pain