Pain

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Pain is the unpleasant and aversive feeling common to such experiences as stubbing a toe, burning a finger, putting iodine on a cut and bumping the "funny bone".[1] The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage".[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] Cultural values, hypnotic suggestion, and cognitive activities such as distraction or appraisal can all significantly modulate pain's intensity and unpleasantness.[6]

Pain is the single most frequent reason for physician consultation in the United States.[7] It is a major symptom in many medical conditions, and can significantly interfere with a person's quality of life and general functioning.[8] Pain medicine is a subspecialty under such medical specialties as anesthesiology, physiatry, neurology, and psychiatry.[9] The study of pain has in recent years attracted many different fields including pharmacology, neurobiology, nursing, dentistry, physiotherapy, and psychology.

Pain
ICD-10 R52
ICD-9 338
DiseasesDB 9503
MedlinePlus 002164
MeSH D010146
Etymology : "Pain (n.) 1297, "punishment," especially for a crime; also (c.1300) "condition one feels when hurt, opposite of pleasure," from O.Fr. peine, from L. poena "punishment, penalty" (in L.L. also "torment, hardship, suffering"), from Gk. poine "punishment," from PIE *kwei- "to pay, atone, compensate" (...)."

Contents

[edit] Types of pain

[edit] Chronic and acute

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,[10] though some theorists and researchers have placed the transition from acute to chronic pain at 12 months.[11] 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.[12] A popular alternative definition of chronic pain, involving no arbitrarily fixed durations is "pain that extends beyond the expected period of healing."[10]

[edit] Classification based on region

Pain can be classed according to its location in the body. Headache, low back pain and pelvic pain are examples.[10]

[edit] Classification based on etiology (cause)

The crudest example of this system 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 physical cause of pain, it is assumed to be the product of psychic conflict or psychopathology.[10] Portenoy divided somatogenic pain into "nociceptive" (caused by activation of nociceptors) and "neuropathic" (caused by damage to or malfunction of the nervous system).[13]

[edit] Classification of nociceptive pain

[edit] Depth

Nociceptive pain can be divided into three types that have distinct organic origins and felt qualities: superficial, deep and visceral. Superficial somatic pain (or cutaneous pain) is caused by injury to the skin or superficial tissues and is a sharp, well-defined, clearly localized pain of short duration. Examples of injuries that produce cutaneous pain include minor wounds and minor (first degree) burns. Deep somatic pain originates from ligaments, tendons, bones, blood vessels, fasciae and muscles, and is a dull, aching, poorly-localized pain of longer duration than cutaneous pain; examples include sprains, broken bones and myofascial pain. Visceral pain originates from the viscera (organs) and is usually more aching or cramping and of a longer duration than somatic pain. Visceral pain may be well-localized, but is often extremely difficult to locate, and several visceral regions produce "referred" pain when injured, where the sensation is located in an area completely unrelated to the site of injury.[14]

[edit] Modality

Nociceptive pain is also classified according to the type of noxious stimulation. The most common categories are thermal (heat or cold), mechanical (crushing, tearing, etc.) and chemical.

[edit] Classification based on body system

"Friction proposed the use of five categories - namely, myofascial, rheumatic, causalgic, neurologic, or vascular."[10]

[edit] IASP Multidiaxial classification system

The International Association for the Study of Pain (IASP) synthesizes much of the above and recommends describing pain according to five categories, or axes:

  • its anatomical location (neck, lower back, etc.)
  • the body system involved (gastrointestinal, nervous, etc.)
  • temporal characteristics (intermittent, constant, etc.)
  • intensity and time since onset
  • etiology (cause)[15]

[edit] Classification based on Mechanism

The IASP system has been criticized by Woolfe and others as inadequate for guiding research and treatment.[16] They propose the development of an additional category based, not on symptoms or underlying conditions, but on the type of neural activity generating the pain.[10]

[edit] Classification based on the MPI

The Multidimensional Pain Inventory (MPI) consists of a set of empirically derived scales designed to assess chronic pain patients' psychosocial state. Turk and Rudy[17] found three types of chronic pain patient: "(a) dysfunctional, patients 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, patients 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."[10] Turk and Okifuji recommend combining MPI characterization of the patient with the IASP multiaxial profile of their pain to arrive at the most useful case description.[10]

[edit] Evolution of the Theory

[edit] Specificity Theory

Descartes' pain pathway.

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.[18]

[edit] Pattern Theory

This 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.[19]

[edit] Gate Control Theory

This all set the scene for Melzack and Wall's classic 1965 Science article "Pain Mechanisms: A New Theory".[20] Here the authors proposed that the large diameter and thin 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 ("touch, pressure, vibration") and thin ("pain") 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.[18]

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 T cell activity and so pain intensity. This model provided a neuroscientific rationale for taking seriously the effect of motivation and cognition on pain.[18]

[edit] The Dimensions of Pain

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,
  • "Cognitive-evaluative" - cognitions such as appraisal, cultural values, distraction and hypnotic suggestion.[21]

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)

[edit] Theory today

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.[22] A-delta and C peripheral nerve fibers carry information regarding the state of the body to the dorsal horn of the spinal cord.[23] Some of these A-delta and C fibers, called nociceptors respond only to painfully intense stimuli, while others do not differentiate noxious from non-noxious stimuli.[22] A.D.Craig and colleagues have identified fibers in the spinal cord dedicated to carrying A-delta fiber pain signals, and others dedicated to carrying C fiber pain signals, from the dorsal horn, up the spinal cord and brain stem, to the thalamus in the brain.[24] 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);[23] and pain that is distinctly located also activates the primary and secondary somatosensory cortices.[25][26]

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,[22] 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.[27] 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.

[edit] Evolutionary and behavioral role

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][28] It is an important part of animal life, vital to healthy survival. People with congenital insensitivity to pain have significantly reduced life expectancy.[29] 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.[30] 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.

[edit] Pain in health care

[edit] Pain as an aid to diagnosis

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 underlying trauma or pathology.

Patient report is the most reliable measure of these factors; health professionals tend to underestimate pain.[31] 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".[32][33] 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.[8] For example, chest pain described as extreme heaviness may indicate myocardial infarction, while chest pain described as tearing may indicate aortic dissection.[34][35]

[edit] Assessment of pain in nonverbal patients

When a patient 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 in or decreased vocalizations, changes in routine behavior patterns and mental status changes.[36] 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 that are vocal but incapable of expressing themselves effectively, such as those with a dementia related diagnosis, an increase in confusion or display of aggressive behaviors, including agitation, may signal that discomfort exists, and further assessment is necessary.[37]

Infants feel pain. Pre-term babies are more sensitive to painful stimuli than full term babies. They lack the verbal skills needed to report pain, so communicate distress by crying. A non-verbal pain assessment should be conducted which should involve the parents, who may have noted changes in the infant not obvious to the health care provider.[38]

[edit] Other barriers to reporting pain

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.[39]

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. Studies have shown that pain is under-treated in north American minorities compared to whites. Many Asians do not want to lose respect in society by admitting they are in pain and need help, believing the pain should be born in silence, while other cultures feel they should report pain right away and get immediate relief.[40] The healthcare provider's cultural background may affect their response to the individual's complaint of pain. This may interfere with treatment of pain.[41] 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.[42]

[edit] Medical treatment and management of pain

Medicine treats injury and pathology to support and speed healing; and treats distressing symptoms, including pain, to relieve suffering during the healing process. When a painful injury or pathology is resistant to treatment and persists, when pain persists after the injury or pathology has healed, and when medical science cannot identify the cause of pain, the task of medicine is to relieve pain. Pain usually resolves promptly once the underlying trauma or pathology has healed, and is treated by one practitioner, with drugs such as analgesics and (occasionally) anxiolytics. The effective management of long term pain, however, frequently requires the coordinated efforts of an interdisciplinary pain management team. The typical pain management team includes a medical practitioner, a clinical psychologist, a physiotherapist, an occupational therapist, and a nurse practitioner.[43] [44]

It is often recognized that a great number of patients suffering from chronic pain are being under-treated because physicians fail to provide comprehensive pain treatment - either due to inadequate training, personal biases or fear of prescription drug abuse.[45]

[edit] Complementary and alternative medicine

A survey of American adults found pain was the most common reason that people use complementary and alternative medicine. Traditional Chinese medicine views pain as a 'blocked' qi, akin to electrical resistance, with treatments such as acupuncture claimed as more effective for nontraumatic pain than traumatic pain. Although the mechanism is not fully understood, acupuncture may stimulate the release of large quantities of endogenous opioids.[46] Pain treatment may be sought through the use of nutritional supplements such as curcumin, glucosamine, chondroitin, bromelain and omega-3 fatty acids. There is interest in the relationship between vitamin D and pain, but the evidence for its relationship to pain, other than in osteomalacia, from controlled trials appears unconvincing.[47] Hypnosis as well as diverse perceptional techniques provoking altered states of consciousness have proven to be of important help in the management of some types of pain in some people.[48] Physical manipulation and exercise are showing interesting results in some pain conditions.[49]

[edit] Special cases

[edit] Phantom pain

Phantom pain is the sensation of pain from a limb or organ that has been lost or from which a person no longer receives physical signals. Phantom limb pain is an experience almost universally reported by amputees and quadriplegics. Phantom pain is a type of neuropathic pain.

[edit] Pain asymbolia

Pain science acknowledges, in a puzzling challenge to IASP definition,[2] 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.[50]

[edit] Insensitivity to pain

The ability to experience pain is essential for protection from injury, and recognition of the presence of injury. Insensitivity to pain may occur in special circumstances, such as for an athlete in the heat of the action, or for an injured soldier happy to leave the battleground. This phenomenon is now explained by the gate control theory. However, insensitivity to pain may also be an acquired impairment following conditions such as spinal cord injury, diabetes mellitus, or more rarely Hansen's Disease (leprosy).[51] A few people can also suffer from congenital insensitivity to pain, or congenital analgesia, a rare genetic defect that puts these individuals at constant risk from the consequences of unrecognized injury or illness. Children with this condition suffer carelessly repeated damages to their tongue, eyes, bones, skin, muscles. They may attain adulthood, but they have a shortened life expectancy.

[edit] Psychogenic pain

Psychogenic pain, also called psychalgia or somatoform pain, is physical pain that is caused, increased, or prolonged by mental, emotional, or behavioral factors.[52][53] Psychogenic pain commonly manifests as headache, back pain, or stomach pain.[52] 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 other sources.

[edit] Society and culture

The okipa ceremony as witnessed by George Catlin, circa 1835.

Physical pain has been diversely understood or defined from antiquity to modern times.[54]

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 pain only with regard to its causal relation to other mental states, sensory inputs, and behavioral outputs.

Religious or secular traditions usually define the nature or meaning of physical pain in every society.[55] Sometimes, extreme practices are highly regarded: mortification of the flesh, painful rites of passage, walking on hot coals, etc.

Variations in pain threshold or in pain tolerance occur between individuals for various reasons including genetics, cultural background, ethnicity and sex.

Physical pain is an important political topic in relation to various issues, including distribution of resources for pain management, drug control, animal rights, torture, pain compliance (see also pain beam, pain maker, pain ray). Corporal punishment is the deliberate infliction of pain intended to punish a person or change his behavior. More generally, it is rather as a part of pain in the broad sense, i.e., suffering, that physical pain is dealt with in cultural, religious, philosophical, or social issues.

[edit] In non-humans

Portrait of René Descartes by Jan Baptist Weenix 1647-1649

As explained above, 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.[56][57] Bernard Rollin of Colorado State University, the principal author of two U.S. federal laws regulating pain relief for animals,[58] 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.[59] 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.[59] 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,[60] some critics continue to question how reliably animal mental states can be determined.[57][61] The ability of invertebrate species of animals, such as insects, to feel pain and suffering is also unclear.[62][63]

Currently the most prevalent attitude is that the presence of pain in an animal, or another human for that matter, cannot be known for certain, but it can be inferred through physical and behavioral reactions.[64] Specialists currently believe that all vertebrates can feel pain, and that certain invertebrates, like the octopus, might too.[65][66] 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,[67] except for instance in fruit flies.[68]

In vertebrates, endogenous opioids are neurochemicals that moderate pain by interacting with opiate receptors. Opioid peptides and opiate receptors occur naturally in crustaceans, and although “at present no certain conclusion can be drawn,”[69] some have interpreted their presence as an indication that lobsters may be able to experience pain.[69][70] The aforementioned Scottish paper holds that lobsters' opioids may "mediate pain in the same way" as in vertebrates.[70] Veterinary medicine uses, for actual or potential animal pain, the same analgesics and anesthetics as used in humans.[71]

[edit] References

  1. ^ The examples represent respectively the three classes of nociceptive pain - mechanical, thermal and chemical - and neuropathic pain.
  2. ^ a b "IASP definition, full entry". http://www.iasp-pain.org/AM/Template.cfm?Section=General_Resource_Links&Template=/CM/HTMLDisplay.cfm&ContentID=3058#Pain. Retrieved 6 October 2009. 
    This often quoted definition was first published in 1979 by IASP in 'Vol 6 of the journal Pain, page 250. It is derived from a definition of pain given earlier by Harold Merskey: "An unpleasant experience that we primarily associate with tissue damage or describe in terms of tissue damage or both." Merskey, H. (1964) An Investigation of Pain in Psychological Illness, DM Thesis, Oxford.
  3. ^ a b Lynn, B. (1984). "Cutaneous nociceptors". in Holden, Arun V.. The neurobiology of pain. Manchester, UK: Manchester University Press. p. 106. ISBN 0-7190-0996-0. http://books.google.com.au/books?id=S7rnAAAAIAAJ&pg=PA106&dq=%22behaviour+designed+to+protect+the+affected+part%22&lr=&client=firefox-a&cd=1#v=onepage&q=%22behaviour%20designed%20to%20protect%20the%20affected%20part%22&f=true. 
  4. ^ Woolf, C.J.; Mannion, R.J. (1999). "Neuropathic pain: aetiology, symptoms, mechanisms and management". The Lancet 353: 1959-1064. PMID 10371588. http://meagherlab.tamu.edu/M-Meagher/%20Health%20Psyc%20630/Readings%20630/Pain%20mech%20read/Woolf%20Lancet%2099.pdf. 
  5. ^ Raj, P. Prithvi (2007). "Taxonomy and classification of pain". in Kreitler, Shulamith; Beltrutti, Diego; Lamberto, Aldo et al.. The handbook of chronic pain. New York: Nova Science Publishers Inc.. ISBN 1-60021-044-9. http://books.google.com.au/books?id=ZG4Svh_UL3UC&pg=PA41&lpg=PA41&dq=%22for+a+significant+number+of+patients+the+pain+never+goes+away.%22+%22but+in+quite+a+few+cases+there+is+no+known+etiology%22&source=bl&ots=3fQ0epQ_NE&sig=IC0YSJv1jwlvloFV9X0DkoWn-tY&hl=en&ei=BS42S6D1J4rg7APW2d2OBg&sa=X&oi=book_result&ct=result&resnum=1&ved=0CAgQ6AEwAA#v=onepage&q=%22for%20a%20significant%20number%20of%20patients%20the%20pain%20never%20goes%20away.%22%20%22but%20in%20quite%20a%20few%20cases%20there%20is%20no%20known%20etiology%22&f=true. 
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  8. ^ a b Breivik, H; Borchgrevink, PC; Allen, SM et al. (2008). "Assessment of pain". British journal of anaesthesia 101 (1): 17-24. doi:10.1093/bja/aen103. PMID 18487245. http://bja.oxfordjournals.org/cgi/reprint/101/1/17.pdf. 
  9. ^ From the American Board of Medical Specialties website: "Pain Medicine is the medical discipline concerned with the diagnosis and treatment of the entire range of painful disorders. (...) Due to the vast scope of the field, Pain Medicine is a multidisciplinary subspecialty (...)."
  10. ^ a b c d e f g h Turk, D.C; Okifuji, A (2001). "Pain terms and taxonomies of pain". in Loeser, J.D; Bonica, J.J.. Bonica's management of pain (3 ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 0683304623. http://books.google.com.au/books?id=TyNEicOiJqQC&pg=RA1-PA18&lpg=RA1-PA18&dq=%22pain+terms+and+taxonomies+of+pain%22&source=bl&ots=wY5rALdI9X&sig=GEaC5_Puz6DbuiGzdrvMLH5w5N0&hl=en&ei=pvs_S8KaJ4rg7APXkajFCg&sa=X&oi=book_result&ct=result&resnum=1&ved=0CAgQ6AEwAA#v=onepage&q=%22pain%20terms%20and%20taxonomies%20of%20pain%22&f=true. 
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