User:Anthonyhcole/Pain

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Anthonyhcole/Pain

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.^[1] It is the feeling common to such experiences as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone".^[2]

Pain motivates us to withdraw from damaging or potentially damaging situations, protect the damaged body part while it heals, and avoid those situations in the future.^[3] It is initiated by stimulation of nociceptors in the peripheral nervous system, or by damage to or malfunction of the peripheral or central nervous systems.^[4]

Most pain resolves promptly once the painful stimulus is removed and the body has healed, but sometimes pain persists despite removal of the stimulus and apparent healing of the body; and sometimes pain arises in the absence of any detectable stimulus, damage or pathology.^[5]

Pain is the most common reason for physician consultation in the United States.^[6] It is a major symptom in many medical conditions, and can significantly interfere with a person's quality of life and general functioning.^[7] Social support, hypnotic suggestion, excitement in sport or war, distraction, and appraisal can all significantly modulate pain's intensity or unpleasantness.^[8][9]

The International Association for the Study of Pain (IASP) classification system recommends describing pain according to five categories: duration and severity, anatomical location, body system involved, cause, and temporal characteristics (intermittent, constant, etc.).^[12] This system has been criticized by Woolf and others as inadequate for guiding research and treatment,^[13] and an additional category based on neurochemical mechanism has been proposed.^[14]

Pain is usually transitory, lasting only until the noxious stimulus is removed or the underlying damage or pathology has healed, but some painful conditions, such as rheumatoid arthritis, peripheral neuropathy, cancer and idiopathic pain, may persist for years. Pain that lasts a long time is called chronic, and pain that resolves quickly is called acute. Traditionally, the distinction between acute and chronic pain has relied upon an arbitrary interval of time from onset; the two most commonly used markers being 3 months and 6 months since the onset of pain,^[14] though some theorists and researchers have placed the transition from acute to chronic pain at 12 months.^[15] Others apply acute to pain that lasts less than 30 days, chronic to pain of more than six months duration, and subacute to pain that lasts from one to six months.^[16] A popular alternative definition of chronic pain, involving no arbitrarily fixed durations is "pain that extends beyond the expected period of healing."^[14] Chronic pain may be divided into "cancer" and "benign".^[16]

Pain can be classed according to its location in the body, as in headache, low back pain and pelvic pain; or according to the body system involved, i.e., myofascial pain (emanating from skeletal muscles or the fibrous sheath surrounding them), rheumatic (emanating from the joints and surrounding tissue), causalgia ("burning" pain in the skin of the arms or, sometimes, legs; thought to be the product of peripheral nerve damage), neuropathic pain (caused by damage to or malfunction of any part of the nervous system), or vascular (pain from blood vessels).^[14]

The crudest example of classification by cause simply distinguishes "somatogenic" pain (arising from a perturbation of the body) from "psychogenic" pain (arising from a perturbation of the mind: when a thorough physical exam, imaging, and laboratory tests fail to detect the cause of pain, it is assumed to be the product of psychic conflict or psychopathology).^[14] Somatogenic pain is divided into "nociceptive" (caused by activation of nociceptors) and "neuropathic" (caused by damage to or malfunction of the nervous system).^[17]

Nociceptive pain is initiated by stimulation of nociceptors, and may be classified according to the mode of noxious stimulation; the most common categories being "thermal" (heat or cold), "mechanical" (crushing, tearing, etc.) and "chemical" (iodine in a cut, chili powder in the eyes).

Nociceptive pain may also be divided into "superficial somatic" and "deep", and deep pain into "deep somatic" and "visceral". Superficial somatic pain is initiated by activation of nociceptors in the skin or superficial tissues, and is sharp, well-defined and clearly located. Examples of injuries that produce superficial somatic pain include minor wounds and minor (first degree) burns. Deep somatic pain is initiated by stimulation of nociceptors in ligaments, tendons, bones, blood vessels, fasciae and muscles, and is dull, aching, poorly-localized pain; examples include sprains and broken bones. Visceral pain originates in the viscera (organs) and often is extremely difficult to locate, and several visceral regions produce "referred" pain when injured, where the sensation is located in an area distant from the site of injury or pathology.^[18]

Neuropathic pain is caused by damage to or malfunction of the nervous system, and is divided into "peripheral" (originating in the peripheral nervous system) and "central" (originating in the brain or spinal cord).^[19] Peripheral neuropathic pain is often described as “burning,” “tingling,” “electrical,” “stabbing,” or “pins and needles.” ^[20] Bumping the "funny bone" elicits peripheral neuropathic pain.

Psychogenic pain, also called psychalgia or somatoform pain, is a sensation of pain caused, increased, or prolonged by mental, emotional, or behavioral factors.^[21][22] Headache, back pain, and stomach pain are sometimes diagnosed as psychogenic.^[21] Sufferers are often stigmatized, because both medical professionals and the general public tend to think that pain from a psychological source is not "real". However, specialists consider that it is no less actual or hurtful than pain from any other source.^[23]

People with long term pain frequently display psychological disturbance, with elevated scores on the Minnesota Multiphasic Personality Inventory scales of hysteria, depression and hypochondriasis (the "neurotic triad"). Some investigators have argued that it is this neuroticism that causes acute injuries to turn chronic, but clinical evidence points the other way, to chronic pain causing neuroticism. When long term pain is relieved by therapeutic intervention, scores on the neurotic triad and anxiety fall, often to normal levels. Self-esteem, often low in chronic pain patients, also shows striking improvement once pain has resolved.^[24]

“The term 'psychogenic' assumes that medical diagnosis is so perfect that all organic causes of pain can be detected; regrettably, we are far from such infallability... All too often, the diagnosis of neurosis as the cause of pain hides our ignorance of many aspects of pain medicine.” Ronald Melzack, 1996.^[24]

Phantom pain is the sensation of pain from a part of the body that has been lost or from which the brain no longer receives physical signals. It is a type of neuropathic pain. Phantom limb pain is a common experience of amputees. One study found that eight days after amputation, 72 per cent of patients had phantom limb pain, and six months later, 65 percent reported it.^[25] Some experience continuous pain that varies in intensity or quality; others experience several bouts a day, or it may occur only once every week or two. It is described as shooting, crushing, burning or cramping. If the pain is continuous for a long period, parts of the intact body may become sensitized, so that touching them evokes pain in the phantom limb, or phantom limb pain may accompany urination or defecation.^[26]

Local anesthetic injections into the nerves or sensitive areas of the stump may relieve pain for days, weeks or, sometimes permanently, despite the drug wearing off in a matter of hours; and small injections of hypertonic saline into the soft tissue between vertebrae produces local pain that radiates into the phantom limb for ten minutes or so and may be followed by hours, weeks or even longer of partial or total relief from phantom pain. Vigorous vibration or electrical stimulation of the stump, or current from electrodes surgically implanted onto the spinal cord all produce relief in some patients.^[26]

Paraplegia, the loss of sensation and voluntary motor control after serious spinal cord damage, may be accompanied by root ("girdle") pain at the level of the spinal cord damage, visceral pain evoked by a filling bladder or bowel, or, in five to ten per cent of paraplegics, phantom body pain in areas of complete sensory loss. Phantom body pain is initially described as burning or tingling but may evolve into severe crushing or pinching pain, fire running down the legs, or a knife twisting in the flesh. Onset may be immediate or may not occur until years after the disabling injury. Surgical treatment rarely provides lasting relief.^[26]

Pain science acknowledges, in a puzzling challenge to IASP definition,^[1] that pain may be experienced as a sensation devoid of any unpleasantness: this happens in a syndrome called pain asymbolia or pain dissociation, caused by conditions like lobotomy, cingulotomy or morphine analgesia. Typically, such patients report that they have pain but are not bothered by it, they recognize the sensation of pain but are mostly or completely immune to suffering from it.^[27]

The ability to experience pain is essential for protection from injury, and recognition of the presence of injury. Episodic analgesia may occur under special circumstances, such as in the excitement of sport or war: a soldier on the battlefield may feel no pain for many hours from a traumatic amputation or other severe injury.^[28] However, insensitivity to pain may also be acquired following conditions such as spinal cord injury, diabetes mellitus, or more rarely Hansen's Disease (leprosy).^[29] A small number of people suffer from congenital analgesia ("congenital insensitivity to pain"), a genetic defect that puts these individuals at constant risk from the consequences of unrecognized injury or illness. Children with this condition suffer carelessly repeated damage to their tongue, eyes, joints, skin, and muscles. They may attain adulthood, but have a shortened life expectancy.

Experimental subjects challenged by acute pain and patients in chronic pain experience impairments in attention control, working memory, mental flexibility, problem solving, and information processing speed.^[30]

In his 1664 Treatise of Man, René Descartes traced a pain pathway. "Particles of heat" (A) activate a spot of skin (B) attached by a fine thread (cc) to a valve in the brain (de) where this activity opens the valve, allowing the animal spirits to flow from a cavity (F) into the muscles that then flinch from the stimulus, turn the head and eyes toward the affected body part, and move the hand and turn the body protectively. The underlying premise of this model - that pain is the direct product of a noxious stimulus activating a dedicated pain pathway, from a receptor in the skin, along a thread or chain of nerve fibers to the pain center in the brain, to a mechanical behavioral response - remained the dominant perspective on pain until the mid-nineteen sixties.^[31]

Specificity theory (dedicated pain receptor and pathway) has been challenged by the theory, proposed initially in 1874 by Wilhelm Erb, that a pain signal can be generated by stimulation of any sensory receptor, provided the stimulation is intense enough: the pattern of stimulation (intensity over time and area), not the receptor type, determines whether nociception occurs. Alfred Goldscheider (1894) proposed that over time, activity from many sensory fibers might accumulate in the dorsal horns of the spinal cord and begin to signal pain once a certain threshold of accumulated stimulation has been crossed. In 1953, Willem Noordenbos observed that a signal carried from the area of injury along large diameter "touch, pressure or vibration" fibers may inhibit the signal carried by the thinner "pain" fibers - the ratio of large fiber signal to thin fiber signal determining pain intensity; hence, we rub a smack. This was taken as a demonstration that pattern of stimulation (of large versus thin fibers in this instance) modulates pain intensity.^[32]

This all set the scene for Melzack and Wall's classic 1965 Science article "Pain Mechanisms: A New Theory".^[33] Here the authors proposed that the large diameter ("touch, pressure, vibration") and thin ("pain") fibers meet at two places in the dorsal horn of the spinal cord: the "transmission" (T) cells, and the "inhibitory" cells. Both large fiber signals and thin fiber signals excite the T cells, and when the output of the T cells exceeds a critical level, pain begins. The job of the inhibitory cells is to inhibit activation of the T cells. The T cells are the gate on pain, and inhibitory cells can shut the gate. If your large diameter and thin fibers have been activated by a noxious event, they will be exciting T cells (opening the pain gate). At the same time, the large diameter fibers will be exciting the inhibitory cells (tending to close the gate), while the thin fibers will be impeding the inhibitory cells (tending to leave the gate open). So, the more large fiber activity relative to thin fiber activity, the less pain you will feel. They had conceived a neural "circuit diagram" to explain why we rub a smack.^[31]

The authors then added the most enduring and influential element of their theory: a pain modulating signal coming down from the brain to the dorsal horn. They pictured the large fiber signals traveling, not only from the site of injury to the inhibitory and T cells in the dorsal horn, but also up to the brain where, depending on the state of the brain, they may trigger a signal back down to the dorsal horn to further modulate inhibitory cell activity and so pain intensity. This model provided a neuroscientific rationale for taking seriously the effect of motivation and cognition on pain intensity.^[31]

In 1968 Melzack and Casey described pain in terms of its three dimensions: "Sensory-discriminative" (sense of the intensity, location, quality and duration of the pain), "Affective-motivational" (unpleasantness and urge to escape the unpleasantness), and "Cognitive-evaluative" (cognitions such as appraisal, cultural values, distraction and hypnotic suggestion).^[9] They theorized that pain intensity (the sensory discriminative dimension) and unpleasantness (the affective-motivational dimension) are not simply determined by the magnitude of the painful stimulus, but “higher” cognitive activities (the cognitive-evaluative dimension) can influence perceived intensity and unpleasantness. Cognitive activities "may affect both sensory and affective experience or they may modify primarily the affective-motivational dimension. Thus, excitement in games or war appears to block both dimensions of pain, while suggestion and placebos may modulate the affective-motivational dimension and leave the sensory-discriminative dimension relatively undisturbed." (p. 432) The paper ended with a call to action: "Pain can be treated not only by trying to cut down the sensory input by anesthetic block, surgical intervention and the like, but also by influencing the motivational-affective and cognitive factors as well." (p. 435)

Specificity, the theory that pain is transmitted from specific pain receptors along dedicated pain fibers to a pain center in the brain, has withstood the challenge from pattern theory, though the "pain center" in the brain has become an elaborate neural network. Wilhelm Erb's (1874) early pattern theory hypothesis, that a pain signal can be generated by intense enough stimulation of any sensory receptor, has been soundly disproved.^[34] A-delta and C peripheral nerve fibers carry information regarding the state of the body to the dorsal horn of the spinal cord.^[35] Some of these A-delta and C fibers (nociceptors) respond only to painfully intense stimuli, while others do not differentiate noxious from non-noxious stimuli.^[34] A.D.Craig and colleagues have identified fibers dedicated to carrying A-delta fiber pain signals, and others dedicated to carrying C fiber pain signals up the spinal cord to the thalamus in the brain.^[36] There is a specific pain pathway from nociceptor to brain. Pain-related activity in the thalamus spreads to the insular cortex (thought to embody, among other things, the feeling that distinguishes pain from other homeostatic emotions such as itch and nausea) and anterior cingulate cortex (thought to embody, among other things, the motivational element of pain);^[35] and pain that is distinctly located also activates the primary and secondary somatosensory cortices.^[37][38]

The gate control theory has not fared well. Most of the dorsal horn interneurons identified by Melzack and Wall as inhibitory are in fact excitatory,^[34] and Koji Inui and colleagues have recently shown that pain reduction due to non-noxious touch or vibration can result from activity within the cerebral cortex, with minimal contribution at the spinal level.^[39] Melzack and Casey's 1968 picture of the dimensions of pain is as influential today as ever, firmly framing theory and guiding research in the functional neuroanatomy and psychology of pain.

Pain is part of the body's defense system, producing a reflexive retraction from the painful stimulus, and tendencies to protect the affected body part while it heals, and avoid that harmful situation in the future.^[3][40] It is an important part of animal life, vital to healthy survival. People with congenital insensitivity to pain have reduced life expectancy.^[41] Idiopathic pain (pain that persists after the trauma or pathology has healed, or that arises without any apparent cause), may be an exception to the idea that pain is helpful to survival, although John Sarno argues that such pain is psychogenic, enlisted as a protective distraction to keep dangerous emotions unconscious.^[42] It is not clear what the survival benefit of some extreme forms of pain (e.g. toothache) might be, and the intensity of some forms of pain (for example as a result of injury to fingernails or toenails) seems to be out of all proportion to any survival benefits.

Variations in pain threshold or in pain tolerance occur between individuals for various reasons including cultural background, ethnicity, genetics, and gender. In pain science, thresholds are measured by gradually increasing the intensity of a stimulus such as electric current or heat applied to the body. The "pain perception threshold" is the point at which the stimulus begins to hurt, and the "tolerance threshold" is reached when the subject acts to stop the pain. There is significant variation in pain perception and tolerance thresholds between cultural groups. For example, people of Mediterranean origin report as painful certain radiant heat intensities that northern Europeans describe as warmth, and Italian women tolerate less electric shock than Jewish or Native American women. Some individuals in all cultures have considerably higher than normal pain perception and tolerance thresholds. For instance, patients who experience painless heart attacks have significantly higher pain thresholds for electric shock, heat and arm-muscle cramp than those who experience painful heart attacks.^[43]

A person's self report is the most reliable measure of pain, with health care professionals tending to underestimate severity.^[44] A definition of pain widely employed in nursing, emphasizing its subjective nature and the importance of believing patient reports, was introduced by Margo McCaffery in 1968: "Pain is whatever the experiencing person says it is, existing whenever he says it does".^[45][46] To assess intensity, the patient may be asked to locate their pain on a scale of 0 to 10, with 0 being no pain at all, and 10 the worst pain they have ever felt. Quality can be established by having the patient complete the McGill Pain Questionnaire indicating which words best describe their pain.^[7]

The Multidimensional Pain Inventory (MPI) is a questionnaire designed to assess the psychosocial state of a person with chronic pain. Analysis of MPI results by Turk and Rudy (1988) found three classes of chronic pain patient: "(a) dysfunctional, people who perceived the severity of their pain to be high, reported that pain interfered with much of their lives, reported a higher degree of psychological distress caused by pain, and reported low levels of activity; (b) interpersonally distressed, people with a common perception that significant others were not very supportive of their pain problems; and (c) adaptive copers, patients who reported high levels of social support, relatively low levels of pain and perceived interference, and relatively high levels of activity."^[47] Combining the MPI characterization of the person with their IASP multiaxial pain profile is recommended for deriving the most useful case description.^[14]

See also: Pain and dementia and Pain in babies

When a person is non-verbal and cannot self report pain, observation becomes critical, and specific behaviors can be monitored as pain indicators. Behaviors such as facial grimacing and guarding indicate pain, as well as an increase or decrease in vocalizations, changes in routine behavior patterns and mental status changes. Patients experiencing pain may exhibit withdrawn social behavior and possibly experience a decreased appetite and decreased nutritional intake. A change in condition that deviates from baseline such as moaning with movement or when manipulating a body part, and limited range of motion are also potential pain indicators. In patients who possess language but are incapable of expressing themselves effectively, such as those with dementia, an increase in confusion or display of aggressive behaviors, including agitation, may signal that discomfort exists, and further assessment is necessary.

Infants feel pain but they lack the language needed to report it, so communicate distress by crying. A non-verbal pain assessment should be conducted involving the parents, who will notice changes in the infant not obvious to the health care provider. Pre-term babies are more sensitive to painful stimuli than full term babies.^[48]

An aging adult may not respond to pain in the way that a younger person would. Their ability to recognize pain may be blunted by illness or the use of multiple prescription drugs. Depression may also keep the older adult from reporting they are in pain. The older adult may also quit doing activities they love because it hurts too much. Decline in self-care activities (dressing, grooming, walking, etc.) may also be indicators that the older adult is experiencing pain. The older adult may refrain from reporting pain because they are afraid they will have to have surgery or will be put on a drug they become addicted to. They may not want others to see them as weak, or may feel there is something impolite or shameful in complaining about pain, or they may feel the pain is deserved punishment for past transgressions.^[49]

Cultural barriers can also keep a person from telling someone they are in pain. Religious beliefs may prevent the individual from seeking help. They may feel certain pain treatment is against their religion. They may not report pain because they feel it is a sign that death is near. Many people fear the stigma of addiction and avoid pain treatment so as not to be prescribed addicting drugs. Many Asians do not want to lose respect in society by admitting they are in pain and need help, believing the pain should be borne in silence, while other cultures feel they should report pain right away and get immediate relief.^[48] Gender can also be a factor in reporting pain. Gender differences are usually the result of social and cultural expectations, with women expected to be emotional and show pain and men stoic, keeping pain to themselves.^[48]

Pain is a symptom of many medical conditions. Knowing the time of onset, location, intensity, pattern of occurrence (continuous, intermittent, etc.), exacerbating and relieving factors, and quality (burning, sharp, etc.) of the pain will help the examining physician to accurately diagnose the problem. For example, chest pain described as extreme heaviness may indicate myocardial infarction, while chest pain described as tearing may indicate aortic dissection.^[50][51]

Medicine treats injury and pathology to promote healing and pain to relieve suffering. Acute pain is usually managed by one practitioner with medications such as analgesics. Management of long term pain, however, frequently benefits from the coordinated efforts of a pain management team.^[52]

Inadequate treatment of pain is widespread in medicine.^[53] Though all ages, ethnicities and genders are undertreated, African and Hispanic Americans as well as women are more often inadequately treated.^[54][55][56]

Suggestion can significantly affect pain intensity. About 35% of people report marked relief after receiving a saline injection they believe to have been morphine. The placebo effect is more pronounced in people who are anxious. Anxiety reduction may, therefore, account for some of the effect. Placebos are more effective on intense pain than mild pain; and they produce progressively weaker effects with repeated administration.^[57]

Individuals with more social support experience less cancer pain, take less pain medication, are less likely to suffer from chest pain after coronary artery bypass surgery, report less labor pain and are less likely to use epidural anesthesia during childbirth.^[58]

To feel pain, one must be conscious of the pain. It is possible for many chronic pain sufferers to become so absorbed in an activity or entertainment that the pain is no longer felt, or is greatly diminished.^[59]

Pain is the most common reason that people use complementary and alternative medicine.^[60][61] An analysis of the 13 highest quality studies of pain treatment with acupuncture, published in January 2009 in the British Medical Journal, concluded there is little difference in the effect of real, sham and no acupuncture.^[62] There is interest in the relationship between vitamin D and pain, but the evidence so far from controlled trials for such a relationship, other than in osteomalacia, is unconvincing.^[63] A 2007 review of 13 studies found evidence for the efficacy of hypnosis in the reduction of pain in some conditions, though the number of patients enrolled in the studies was low, bringing up issues of power to detect group differences, and most lacked credible controls for placebo and/or expectation. The authors concluded that "although the findings provide support for the general applicability of hypnosis in the treatment of chronic pain, considerably more research will be needed to fully determine the effects of hypnosis for different chronic-pain conditions." (p. 283)^[64]

Pain is the main reason for visiting the emergency department in more than 50% of cases^[65] and is present in 30% of family practice visits.^[66] Chronic pain is believed to affect 12-80% ^[vague] of the population.^[67]

The nature or meaning of physical pain has been diversely understood by religious or secular traditions from antiquity to modern times.^[68][69]

Physical pain is an important political topic in relation to various issues, including pain management policy, drug control, animal rights, torture, pain compliance. In various contexts, the deliberate infliction of pain in the form of corporal punishment is used as retribution for an offence, or for the purpose of disciplining or reforming a wrongdoer, or to deter attitudes or behaviour deemed unacceptable. In some cultures, extreme practices such as mortification of the flesh or painful rites of passage are highly regarded.

Philosophy of pain is a branch of philosophy of mind that deals essentially with physical pain. Identity theorists assert that the mental state of pain is completely identical with some physiological state. Functionalists consider that pain as a mental state is constituted solely by its functional role, by its causal relations to other mental states, sensory inputs, and behavioral outputs.

More generally, it is often as a part of pain in the broad sense, i.e., suffering, that physical pain is dealt with in culture, religion, philosophy, or society.

The most reliable method for assessing pain in most humans is by asking a question: a person may report pain that cannot be detected by any known physiological measure. However, like infants (Latin infans meaning "unable to speak"), non-human animals cannot answer questions about whether they feel pain; thus the defining criterion for pain in humans cannot be applied to them. Philosophers and scientists have responded to this difficulty in a variety of ways. René Descartes for example argued that animals lack consciousness and therefore do not experience pain and suffering in the way that humans do.^[70][71] Bernard Rollin of Colorado State University, the principal author of two U.S. federal laws regulating pain relief for animals,^[72] writes that researchers remained unsure into the 1980s as to whether animals experience pain, and that veterinarians trained in the U.S. before 1989 were simply taught to ignore animal pain.^[73] In his interactions with scientists and other veterinarians, he was regularly asked to "prove" that animals are conscious, and to provide "scientifically acceptable" grounds for claiming that they feel pain.^[73] Carbone writes that the view that animals feel pain differently is now a minority view. Academic reviews of the topic are more equivocal, noting that although the argument that animals have at least simple conscious thoughts and feelings has strong support,^[74] some critics continue to question how reliably animal mental states can be determined.^[71][75] The ability of invertebrate species of animals, such as insects, to feel pain and suffering is also unclear.^[76][77]

The presence of pain in an animal cannot be known for certain, but it can be inferred through physical and behavioral reactions.^[78] Specialists currently believe that all vertebrates can feel pain, and that certain invertebrates, like the octopus, might too.^[79][80] As for other animals, plants, or other entities, their ability to feel physical pain is at present a question beyond scientific reach, since no mechanism is known by which they could have such a feeling. In particular, there are no known nociceptors in groups such as plants, fungi, and most insects,^[81] except for instance in fruit flies.^[82]

In vertebrates, endogenous opioids are neurochemicals that moderate pain by interacting with opiate receptors. Opioids and opiate receptors occur naturally in crustaceans and, although at present no certain conclusion can be drawn,^[83] their presence indicates that lobsters may be able to experience pain.^[83][84] Opioids may mediate their pain in the same way as in vertebrates.^[84] Veterinary medicine uses, for actual or potential animal pain, the same analgesics and anesthetics as used in humans.^[85]

• Pain Journal of the IASP
• Pain Stanford Encyclopedia of Philosophy