Pain

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Symptom/Sign: Pain
Classifications and external resources
ICD-10 R52
ICD-9 338
DiseasesDB 9503
MedlinePlus 002164
MeSH D010146

Pain, in the sense of physical pain,[1] is a typical sensory experience that may be described as the unpleasant awareness of a noxious stimulus or bodily harm. Individuals get acquainted to pain through various daily hurts and aches, and occasionally through more serious injuries or illnesses. For scientific and clinical purposes, pain is defined by the International Association for the Study of Pain (IASP) as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage".[2][3]

Pain is highly subjective to the individual experiencing it. A definition that is widely used in nursing was first given as early as 1968 by Margo McCaffery: "'Pain is whatever the experiencing person says it is, existing whenever he says it does".[4][5]

Pain of any type is the most frequent reason for physician consultation in the United States, prompting half of all Americans to seek medical care annually.[6] It is a major symptom in many medical conditions, significantly interfering with a person's quality of life and general functioning. Diagnosis is based on characterizing pain in various ways, according to duration, intensity, type (dull, burning or stabbing), source, or location in body. Usually pain stops without treatment or responds to simple measures such as resting or taking an analgesic, and it is then called ‘acute’ pain. But it may also become intractable and develop into a condition called chronic pain, in which pain is no longer considered a symptom but an illness by itself. The study of pain has in recent years attracted many different fields such as pharmacology, neurobiology, nursing sciences, dentistry, physiotherapy, and psychology. Pain medicine is a separate subspecialty[7] figuring under some medical specialties like anesthesiology, physiatry, neurology, psychiatry.

Pain is part of the body's defense system, triggering a reflex reaction to retract from a painful stimulus, and helps adjust behaviour to increase avoidance of that particular harmful situation in the future. Given its significance, physical pain is also linked to various cultural, religious, philosophical, or social issues.

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" (...)."
Online Etymology Dictionary

Contents

[edit] Clarification on the use of certain pain-related terms

  • The word pain used without a modifier usually refers to physical pain, but it may also refer to pain in the broad sense, i.e. suffering. The latter includes physical pain and mental pain, or any unpleasant feeling, sensation, and emotion. It may be described as a private feeling of unpleasantness and aversion associated with harm or threat of harm in an individual. Care should be taken to make the appropriate distinction when required between the two meanings. For instance, philosophy of pain is essentially about physical pain, while a philosophical outlook on pain is rather about pain in the broad sense. Or, as another quite different instance, nausea or itch are not 'physical pains', but they are unpleasant sensory or bodily experience, and a person 'suffering' from severe or prolonged nausea or itch may be said 'in pain'.
  • Nociception, the unconscious activity induced by a harmful stimulus in sense receptors, peripheral nerves, spinal column and brain, should not be confused with physical pain, which is a conscious experience.[8]
  • Qualifiers, such as mental, emotional, psychological, and spiritual, are often used for referring to more specific types of pain or suffering. In particular, 'mental pain' may be used in relationship with 'physical pain' for distinguishing between two wide categories of pain. A first caveat concerning such a distinction is that it uses 'physical pain' in a sense that normally includes not only the 'typical sensory experience' of 'physical pain' but also other unpleasant bodily experience such as itch or nausea. A second caveat is that the terms physical or mental should not be taken too literally: physical pain, as a matter of fact, happens through conscious minds and involves emotional aspects, while mental pain happens through physical brains and, being an emotion, it involves important bodily physiological aspects.
  • The term unpleasant or unpleasantness commonly means painful or painfulness in a broad sense. It is also used in (physical) pain science for referring to the affective dimension of pain, usually in contrast with the sensory dimension. For instance: “Pain-unpleasantness is often, though not always, closely linked to both the intensity and unique qualities of the painful sensation.”[9] Pain science acknowledges, in a puzzling challenge to IASP definition, that pain may be experienced as a sensation devoid of any unpleasantness: see below pain asymbolia.[10]
  • Suffering is sometimes used in the specific narrow sense of physical pain, but more often it refers to mental pain, or more often yet to pain in the broad sense. Suffering is described as an individual's basic affective experience of unpleasantness and aversion associated with harm or threat of harm.

The terms pain and suffering are often used together in different senses which can become confusing, for example:

  • being used as synonyms;
  • being used in contradistinction to one another: e.g. "pain is inevitable, suffering is optional", or "pain is physical, suffering is mental";
  • being used to define each other: e.g. "pain is physical suffering", or "suffering is severe physical or mental pain".

To avoid confusion: this article is about physical pain in the narrow sense of a typical sensory experience associated with actual or potential tissue damage. This excludes pain in the broad sense of any unpleasant experience, which is covered in detail by the article Suffering.

[edit] Mechanism

Stimulation of a nociceptor, due to a chemical, thermal, or mechanical event that has the potential to damage body tissue, may cause nociceptive pain.

Damage to the nervous system itself, due to disease or trauma, may cause neuropathic (or neurogenic) pain.[11] Neuropathic pain may refer to peripheral neuropathic pain, which is caused by damage to nerves, or to central pain, which is caused by damage to the brain, brainstem, or spinal cord.

Nociceptive pain and neuropathic pain are the two main kinds of pain when the primary mechanism of production is considered. A third kind may be mentioned: see below the rare case of psychogenic pain.

Nociceptive pain may be classified further in three types that have distinct organic origins and felt qualities.[12]

  1. Superficial somatic pain (or cutaneous pain) is caused by injury to the skin or superficial tissues. Cutaneous nociceptors terminate just below the skin, and due to the high concentration of nerve endings, produce a sharp, well-defined, localized pain of short duration. Examples of injuries that produce cutaneous pain include minor wounds, and minor (first degree) burns.

  2. Deep somatic pain originates from ligaments, tendons, bones, blood vessels, fasciae, and muscles. It is detected with somatic nociceptors. The scarcity of pain receptors in these areas produces a dull, aching, poorly-localized pain of longer duration than cutaneous pain; examples include sprains, broken bones, and myofascial pain.

  3. Visceral pain originates from body's viscera, or organs. Visceral nociceptors are located within body organs and internal cavities. The even greater scarcity of nociceptors in these areas produces pain that is usually more aching or cramping and of a longer duration than somatic pain. Visceral pain may be well-localized, but often it is extremely difficult to localize, and several injuries to visceral tissue exhibit "referred" pain, where the sensation is localized to an area completely unrelated to the site of injury.

Nociception is the unconscious afferent activity produced in the peripheral and central nervous system by stimuli that have the potential to damage tissue. It should not be confused with pain, which is a conscious experience.[8] It is initiated by nociceptors that can detect mechanical, thermal or chemical changes above a certain threshold. All nociceptors are free nerve endings of fast-conducting myelinated A delta fibers or slow-conducting unmyelinated C fibers, respectively responsible for fast, localized, sharp pain and slow, poorly-localized, dull pain. Once stimulated, they transmit signals that travel along the spinal cord and within the brain. Nociception, even in the absence of pain, may trigger withdrawal reflexes and a variety of autonomic responses such as pallor, diaphoresis, bradycardia, hypotension, lightheadedness, nausea and fainting.[13]

Brain areas that are particularly studied in relation with pain include the somatosensory cortex which mostly accounts for the sensory discriminative dimension of pain, and the limbic system, of which the thalamus and the anterior cingulate cortex are said to be especially involved in the affective dimension.

The gate control theory of pain describes how the perception of pain is not a direct result of activation of nociceptors, but instead is modulated by interaction between different neurons, both pain-transmitting and non-pain-transmitting. In other words, the theory asserts that activation, at the spine level or even by higher cognitive brain processes, of nerves or neurons that do not transmit pain signals can interfere with signals from pain fibers and inhibit or modulate an individual's experience of pain.

Pain may be experienced differently depending on genotype; as an example individuals with red hair may be more susceptible to pain caused by heat,[14] but redheads with a non-functional melanocortin 1 receptor (MC1R) gene are less sensitive to pain from electric shock.[15] Gene Nav1.7 has been identified as a major factor in the development of the pain-perception systems within the body. A rare genetic mutation in this area causes non-functional development of certain sodium channels in the nervous system, which prevents the brain from receiving messages of physical damage, resulting in congenital insensitivity to pain.[16] The same gene also appears to mediate a form of pain hyper-sensitivity, while other mutations may be the root of paroxysmal extreme pain disorder.[16][17]

[edit] Evolutionary and behavioral role

Pain is part of the body's defense system, triggering mental and physical behavior to end the painful experience. It promotes learning so that repetition of the painful situation will be less likely.

Despite its unpleasantness, pain is an important part of the existence of humans and other animals; in fact, it is vital to healthy survival (see below Insensitivity to pain). Pain encourages an organism to disengage from the noxious stimulus associated with the pain. Preliminary pain can serve to indicate that an injury is imminent, such as the ache from a soon-to-be-broken bone. Pain may also promote the healing process, since most organisms will protect an injured region in order to avoid further pain.

Interestingly, the brain itself is devoid of nociceptive tissue, and hence cannot experience pain. Thus, a headache is not due to stimulation of pain fibers in the brain itself. Rather, the membrane surrounding the brain and spinal cord, called the dura mater, is innervated with pain receptors, and stimulation of these dural nociceptors is thought to be involved to some extent in producing headache pain. The vasoconstriction of pain-innervated blood vessels in the head is another common cause. Some evolutionary biologists have speculated that this lack of nociceptive tissue in the brain might be because any injury of sufficient magnitude to cause pain in the brain has a sufficiently high probability of being fatal that development of nociceptive tissue therein would have little to no survival benefit.

Chronic pain, in which the pain becomes pathological rather than beneficial, may be an exception to the idea that pain is helpful to survival, although some specialists believe that psychogenic chronic pain exists as a protective distraction to keep dangerous repressed emotions such as anger or rage unconscious.[18] 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) seem to be out of all proportion to any survival benefits.

[edit] Diagnosis

To establish an understanding of an individual's pain, health-care practitioners will typically try to establish certain characteristics of the pain:

  • Quality
  • Intensity
  • Localization
  • Radiation
  • Frequency and Duration
  • Onset and Offset
  • Exacerbating Factors
  • Ameliorating Factors

By using the gestalt of these characteristics, the source or cause of the pain can often be established. A complete diagnosis of pain will require also to look at the patient's general condition, symptoms, and history of illness or surgery. The physician may order blood tests, X-rays, scans, EMG, etc. Pain clinics may investigate the person's psychosocial history and situation.

Pain assessment also uses the concepts of pain threshold, the least experience of pain which a subject can recognize, and pain tolerance, the greatest level of pain which a subject is prepared to tolerate. Among the most frequent technical terms for referring to abnormal perturbations in pain experience, there are:

  • allodynia, pain due to a stimulus which does not normally provoke pain,
  • hyperalgesia, an increased response to a stimulus which is normally painful,
  • hypoalgesia, diminished pain in response to a normally painful stimulus.[19]

[edit] Verbal characterization

The quality of the pain remains a key characteristic, and is often the first question a practitioner will ask. Typical descriptions of pain quality include sharp, stabbing, tearing, squeezing, cramping, burning, lancinating (electric-shock like), or heaviness. It may be experienced as throbbing, dull, nauseating, shooting or a combination of these. Indeed, individuals who are clearly in extreme distress such as from a myocardial infarction may not describe the sensation as pain, but instead as an extreme heaviness on the chest. Another individual with pain in the same region and with the same intensity may describe the pain as tearing which would lead the practitioner to consider aortic dissection. Inflammatory pain is commonly associated with some degree of itch sensation, leading to a chronic urge to rub or otherwise stimulate the affected area. The difference between these diagnoses and many others rests on the quality of the pain. The McGill Pain Questionnaire is an instrument often used for verbal assessment of pain.

[edit] Intensity

Pain may range in intensity from slight through severe to agonizing and can appear as constant or intermittent. The threshold of pain varies widely between individuals. Many attempts have been made to create a pain scale that can be used to quantify pain, for instance on a numeric scale that ranges from 1 to 10 points. The purpose of these scales is to monitor an individual's pain over time, allowing care-givers to see how a patient responds to therapy for example. Accurate quantification can also allow researchers to compare results between groups of patients.

[edit] Localization

Pains are usually called according to their subjective localization in a specific area or region of the body: headache, toothache, shoulder pain, abdominal pain, back pain, joint pain, myalgia, etc. Localization is not always accurate in defining the problematic area, although it will often help narrow the diagnostic possibilities. Some pain sensations may be diffuse (radiating) or referred. Radiation of pain occurs in neuralgia when stimulus of a nerve at one site is perceived as pain in the sensory distribution of that nerve. Sciatica, for instance, involves pain running down the back of the buttock, leg and bottom of foot that results from compression of a nerve root in the lumbar spine. Referred pain usually happens when sensory fibres from the viscera enter the same segment of the spinal cord as somatic nerves i.e. those from superficial tissues. The sensory nerve from the viscera stimulates the nearby somatic nerve so that the pain localization in the brain is confused. A well-known example is when heart damage is perceived as pain the left shoulder or arm.[20]

[edit] Management

Main article: Pain management

Medical management of pain has given rise to a distinction between acute pain and chronic pain. Acute pain is 'normal' pain, it is felt when hurting a toe, breaking a bone, having a toothache, or walking after an extensive surgical operation. Chronic pain is a 'pain illness', it is felt day after day, month after month, and seems impossible to heal.

In general, physicians are more comfortable treating acute pain, which usually is caused by soft tissue damage, infection and/or inflammation among other causes. It is usually treated simultaneously with pharmaceuticals, commonly analgesics, or appropriate techniques for removing the cause and for controlling the pain sensation. The failure to treat acute pain properly may lead to chronic pain in some cases.[21]

General physicians have only elementary training in chronic pain management. Often, patients suffering from it are referred to various medical specialists. Though usually caused by an injury, an operation, or an obvious illness, chronic pain may as well have no apparent cause, or may be caused by a developing illness or imbalance. This disorder can trigger multiple psychological problems that confound both patient and health care providers, leading to various differential diagnoses and to patient's feelings of helplessness and hopelessness. Multidisciplinary pain clinics are growing in number since a few decades.

[edit] Anesthesia

Anesthesia is the condition of having the feeling of pain and other sensations blocked by drugs that induces a lack of awareness. It may be a total or a minimal lack of awareness throughout the body (i.e. general anesthesia), or a lack of awareness in a part of the body (i.e. regional or local anesthesia).

[edit] Analgesia

Analgesia is an alteration of the sense of pain without loss of consciousness. The body possesses an endogenous analgesia system, which can be supplemented with painkillers or analgesic drugs to regulate nociception and pain. Analgesia may occur in the central nervous system or in peripheral nerves and nociceptors. The perception of pain can also be modified by the body according to the gate control theory of pain.

The endogenous central analgesia system is mediated by 3 major components : the periaquaductal grey matter, the nucleus raphe magnus and the nociception inhibitory neurons within the dorsal horns of the spinal cord, which act to inhibit nociception-transmitting neurons also located in the spinal dorsal horn. The peripheral regulation consists of several different types of opioid receptors that are activated in response to the binding of the body's endorphins. These receptors, which exist in a variety of areas in the body, inhibit firing of neurons that would otherwise be stimulated to do so by nociceptors.[citation needed]

The gate control theory of pain postulates that nociception is "gated" by non-noxious stimuli such as vibration. Thus, rubbing a bumped knee seems to relieve pain by preventing its transmission to the brain. Pain is also "gated" by signals that descend from the brain to the spinal cord to suppress (and in other cases enhance) incoming nociceptive information.

[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.[22]

Pain treatment may be sought through the use of nutritional supplements such as curcumin, glucosamine, chondroitin, bromelain and omega-3 fatty acids.

Hypnosis as well as diverse perceptional techniques provoking altered states of consciousness have proven to be of important help in the management of all types of pain.[23]

Some kinds of physical manipulation or exercise are showing interesting results as well.[24]

[edit] Special cases

[edit] Phantom pain

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

[edit] Pain asymbolia

Pain science acknowledges, in a puzzling challenge to IASP definition,[3] 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.[10]

[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[25]. 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, or psychalgia, is pain which to the sufferer is indistinct from actual physical pain, but which is caused by a psychological process. It occurs rarely, and generally in persons with a mental disorder. Currently, it is considered as physical pain, in conformity with IASP definition of pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" (emphasis added).[3]

Physical pain accompanying or induced by heartache, rejection, depression, or other such mental events, is not usually considered as psychogenic pain.

[edit] Pain as pleasure

See algolagnia and sadomasochism.

[edit] Society and culture

Physical pain has been diversely understood or defined from antiquity to modern times.[26]

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 physical state caused by various physiological causes. Functionalists consider pain to be defined completely by its causal role and nothing else.

Religious or secular traditions usually define the nature or meaning of physical pain in every society.[27] 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 because of genetics, but also according to cultural, ethnical, or gender background.

Physical pain is an important political topic in relation with various issues, including resources distribution for pain management, drug control, 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 a his/her behavior. Historically speaking, most punishments, whether in judicial, domestic, or educational settings, were corporal in basis.

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 other species

It is not scientifically possible to prove whether an animal, or a human for that matter, experiences pain or not. However, the presence of pain can be inferred through physical and behavioral reactions.[28] Specialists currently believe that all vertebrates can feel pain, and that certain invertebrates, like the octopus, might too. As for other animals, plants, or other entities, their ability to feel physical pain is presently a question beyond the scientific reach.

Veterinary medicine uses, for actual or potential animal pain, the same analgesics and anesthetics as used in humans.[29]


[edit] Notes and references

  1. ^ See section Clarification on the use of certain pain-related terms.
  2. ^ This often quoted definition was first published in 1979 by IASP in Pain journal, number 6, 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 c See IASP Pain Terminology. The whole entry on the term pain itself reads like this:

    Pain. An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Note: The inability to communicate verbally does not negate the possibility that an individual is experiencing pain and is in need of appropriate pain-relieving treatment. Pain is always subjective. Each individual learns the application of the word through experiences related to injury in early life. Biologists recognize that those stimuli which cause pain are liable to damage tissue. Accordingly, pain is that experience we associate with actual or potential tissue damage. It is unquestionably a sensation in a part or parts of the body, but it is also always unpleasant and therefore also an emotional experience. Experiences which resemble pain but are not unpleasant, e.g., pricking, should not be called pain. Unpleasant abnormal experiences (dysesthesias) may also be pain but are not necessarily so because, subjectively, they may not have the usual sensory qualities of pain. Many people report pain in the absence of tissue damage or any likely pathophysiological cause; usually this happens for psychological reasons. There is usually no way to distinguish their experience from that due to tissue damage if we take the subjective report. If they regard their experience as pain and if they report it in the same ways as pain caused by tissue damage, it should be accepted as pain. This definition avoids tying pain to the stimulus. Activity induced in the nociceptor and nociceptive pathways by a noxious stimulus is not pain, which is always a psychological state, even though we may well appreciate that pain most often has a proximate physical cause.

  4. ^ McCaffery M. Nursing practice theories related to cognition, bodily pain, and man-environment interactions. LosAngeles: UCLA Students Store. 1968.
  5. ^ More recently, McCaffery defined pain as "whatever the experiencing person says it is, existing whenever the experiencing person says it does.” Pasero, Chris; McCaffery, Margo (1999). Pain: clinical manual. St. Louis: Mosby. ISBN 0-8151-5609-X. .
  6. ^ National Pain Education Council
  7. ^ 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 (...)."
  8. ^ a b "Activity induced in the nociceptor and nociceptive pathways by a noxious stimulus is not pain, which is always a psychological state, even though we may well appreciate that pain most often has a proximate physical cause." Source: IASP Pain Terminology.
  9. ^ Donald D. Price, Central Neural Mechanisms that Interrelate Sensory and Affective Dimensions of Pain, ‘’Molecular Interventions’’ 2:392-403 (2002)
  10. ^ a b Nikola Grahek, Feeling pain and being in pain, Oldenburg, 2001. ISBN 3-8142-0780-7.
  11. ^ Compare definitions at IASP Pain Terminology: "Neurophathic pain —– Pain initiated or caused by a primary lesion or dysfunction in the nervous system." and "Neurogenic pain — Pain initiated or caused by a primary lesion, dysfunction, or transitory perturbation in the peripheral or central nervous system."
  12. ^ Pain Physiology
  13. ^ Feinstein B, J Langton, R Jameson, F Schiller. Experiments on pain referred from deep somatic tissues. J Bone Joint Surg 1954;36-A(5):981-97.
  14. ^ Liem EB, Joiner TV, Tsueda K, Sessler DI (2005). "Increased sensitivity to thermal pain and reduced subcutaneous lidocaine efficacy in redheads". Anesthesiology 102 (3): 509-14. PMID 15731586. 
  15. ^ Mogil JS, Ritchie J, Smith SB, et al (2005). "Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans". J. Med. Genet. 42 (7): 583-7. doi:10.1136/jmg.2004.027698. PMID 15994880. 
  16. ^ a b Fertleman CR, Baker MD, Parker KA, et al (2006). "SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes". Neuron 52 (5): 767-74. doi:10.1016/j.neuron.2006.10.006. PMID 17145499. 
  17. ^ Hopkin, M. "The mutation that takes away pain", Nature News, 2006-12-13. Retrieved on 2008-03-29. 
  18. ^ Sarno, John E., MD, et al., The Divided Mind: The Epidemic of Mindbody Disorders 2006 (ISBN 0-06-085178-3)
  19. ^ IASP Pain Terminology.
  20. ^ Ann Waugh, Allison Grant (2001). Anatomy and Physiology in Health and Illness. Edinburgh: Churchill Livingstone, pp 174-175. ISBN 0443-06468 7. 
  21. ^ Dahl JB, Moiniche S (2004). "Pre-emptive analgesia". Br Med Bull 71: 13-27. PMID 15596866. 
  22. ^ Sapolsky, Robert M. (1998). Why zebras don't get ulcers: An updated guide to stress, stress-related diseases, and coping. New York: W.H. Freeman and CO. ISBN 0-585-36037-5. 
  23. ^ Robert Ornstein PhD, David Sobel MD (1988). The Healing Brain. New York: Simon & Schuster Inc, pp 98-99. ISBN 0-671-66236-8. 
  24. ^ Douglas E DeGood, Donald C Manning MD, Susan J Middaugh (1997). The headache & Neck Pain Workbook. Oakland, California: New Harbinger Publications. ISBN 1-57224-086-5. 
  25. ^ Brand, Paul; Philip Yancey (c1997). The gift of pain : why we hurt & what we can do about it. Zondervan Publ.. ISBN 0-310-22144-7. 
  26. ^ Rey, Roselyne (1995). The history of pain. Cambridge: Harvard University Press. ISBN 0-674-39968-4. 
  27. ^ Morris, David Rae (1991). The culture of pain. Berkeley: University of California Press. ISBN 0-520-08276-1. 
  28. ^ Abbott FV, Franklin KB, Westbrook RF (January 1995). "The formalin test: scoring properties of the first and second phases of the pain response in rats". Pain 60 (1): 91–102. PMID 7715946. 
  29. ^ Viñuela-Fernández I, Jones E, Welsh EM, Fleetwood-Walker SM (September 2007). "Pain mechanisms and their implication for the management of pain in farm and companion animals". Vet. J. 174 (2): 227–39. doi:10.1016/j.tvjl.2007.02.002. PMID 17553712. 

[edit] External links

Look up pain, nociception, painful, hurting, dolor in Wiktionary, the free dictionary.