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(Redirected from Nociception)
'Pain' is an unpleasant sensation. It 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”.
'Nociception'[1] (sometimes also called ''nociperception''[2]) is a measurable physiological event of a type usually associated with pain.
Scientifically, ''pain'' (a subjective experience) is separate and distinct from ''nociception'', the system which carries information about inflammation, damage or near-damage in tissue, to the spinal cord and brain. Nociception frequently occurs without pain being felt and can convey information without conscious awareness. Conversely, but less frequently, a sensation of pain can exist in the absence of nociception.
Pain is part of the body's defense system: it triggers mental problem-solving strategies that seek to end the painful experience, and it promotes learning, making repetition of the painful situation less likely. The nociceptive system transmits signals that usually trigger the sensation of pain, it is a critical component of the body's ability to react to damaging stimuli and it is part of a rapid-warning relay instructing the central nervous system to initiate reactions for minimizing injury.
Pain may range in intensity from slight through severe to agonizing. It is experienced as having qualities such as sharp, throbbing, dull, nauseating, burning and shooting. It often has both an emotional quality and a sensed bodily location. Medical professionals will sometimes ask patients to rate their pain on a scale of zero through ten, where ten is consistent with screaming and thrashing about.
This subjective reality of the localisation of pain to an area of the body is the basis for speaking of ''pain receptor, neck pain, referred pain, cutaneous pain,'' as well as ''pain in my foot'', ''kidney pain,'' or the ''painful uterine contractions'' occurring during childbirth. This common usage of ''pain'' is not entirely consistent with the scientists' model of pain being a subjective experience.
Inability to experience pain, as in the rare condition congenital insensitivity to pain or congenital analgesia, can cause various health problems.
Pain can be classified as ''acute'' or ''chronic.'' The distinction between acute and chronic pain is not based on its duration of sensation, but rather the nature of the pain itself. In general, physicians are more comfortable treating acute pain, which has as its source soft tissue damage, infection and/or inflammation. It can be modulated and removed by treating its cause and through combined strategies using analgesics to treat the pain and antibiotics to treat the infection. In general, while it is uncomfortable to experience, it is easy to treat; is distinguished by having a specific cause and purpose, and generally produces no persistent psychological reaction. Physicians are more likely to prescribe medications to treat acute pain, particularly in those situations when they are satisfied that they understand the pain's origin and believe the pain will be short in duration. This is why a patient might leave the hospital with two weeks' worth of adequate pain medicine, but the same medications may not be readily prescribed if the patient's pain lasts beyond an expected period of time. It is not the pain itself that is short in duration: it is the diagnosis of "acute pain" and the expectation that it will be short in nature that continues to confuse both the medical establishment and those who experience pain.
The primary distinction is this: acute pain serves to protect one after an injury. Chronic pain does not serve this or any other purpose. Acute pain is the symptom of pain. Chronic pain is the disease of pain.
American pain associations estimate that 40-80 million Americans live with chronic pain. At the same time, there are only 8,000 qualified pain management specialists. Many physicians faced with patients who live with chronic pain have had no professional training in pain management. It is not regularly taught in medical school, and even recent legislation in some states to ensure that physicians receive continuing education in pain medicine and end-of-life care do not guarantee proper training in pain. In many states, there remains no legislation ensuring that licensed physicians, even those who work in hospital emergency rooms, have any pain management training whatsoever.
Chronic pain has no time limit, often has no apparent cause and serves no apparent biological purpose. Chronic pain can trigger multiple psychological problems that confound both patient and health care provider, leading to feelings of helplessness and hopelessness. The most common causes of chronic pain include low-back pain, headache, recurrent facial pain, cancer pain, and arthritic pain. Sometimes chronic pain can have a psychosomatic or psychogenic cause.[3]
Chronic pain was originally defined as pain that has lasted 6 months or longer. It is now defined as "the disease of pain." Its origin, duration, intensity, and specific symptoms vary. The one consistent fact of chronic pain is that, as a disease, it cannot be understood in the same terms as acute pain, and the failure to make this distinction (particularly in those who suffer chronic pain) has been and continues to be the cause of multi-dimensional suffering, depression, social isolation, and helplessness. The failure to recognize chronic pain as substantially different from acute pain cannot be blamed on the medical profession: it is a societal lapse.
Chronic pain, no matter how debilitating it is in one's life, continues to be considered by most insurance carriers as a 3-17% disability.
There have been some theories that not treating acute pain properly can lead to chronic pain.[4]
The experience of physiological pain can be grouped according to the source and related nociceptors (pain-detecting neurons).
★ '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 well-defined, localized pain of short duration. Examples of injuries that produce cutaneous pain include paper cuts, minor cuts, minor (first degree) burns and lacerations.
★ 'Somatic pain' originates from ligaments, tendons, bones, blood vessels, and even nerves themselves. It is detected with somatic nociceptors. The scarcity of pain receptors in these areas produces a dull, poorly-localized pain of longer duration than cutaneous pain; examples include sprains and broken bones. Myofascial pain usually is caused by trigger points in muscles, tendons and fascia, and may be local or referred.
★ '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 and of a longer duration than somatic pain. Visceral pain 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. Myocardial ischaemia (the loss of blood flow to a part of the heart muscle tissue) is possibly the best known example of referred pain; the sensation can occur in the upper chest as a restricted feeling, or as an ache in the left shoulder, arm or even hand. "The brain freeze" is another example of referred pain, in which the vagus nerve is cooled by cold inside the throat. Referred pain can be explained by the findings that pain receptors in the viscera also excite spinal cord neurons that are excited by cutaneous tissue. Since the brain normally associates firing of these spinal cord neurons with stimulation of somatic tissues in skin or muscle, pain signals arising from the viscera are interpreted by the brain as originating from the skin. The theory that visceral and somatic pain receptors converge and form synapses on the same spinal cord pain-transmitting neurons is called "Ruch's Hypothesis".
★ 'Phantom limb pain', a type of referred 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.
★ 'Neuropathic pain', can occur as a result of injury or disease to the nerve tissue itself. This can disrupt the ability of the sensory nerves to transmit correct information to the thalamus, and hence the brain interprets painful stimuli even though there is no obvious or known physiologic cause for the pain. Neuropathic pain is, as stated above, the disease of pain. It is not the sole definition for chronic pain, but does meet its criteria.
Visceral pain sensation is often referred by the CNS to a dermatome region which may be far away from the originating organ. These correlate to the position of the organ in the embryo. Examples of this include the heart which originates in the neck, thus producing the classical pain and arm pain experienced during acute cardiac pain.
★ Jaw - Temporal arteritis (serious), trauma
★ Ear - otitis media (very common esp. in children), otitis externa, trauma
★ Eye - glaucoma, trauma
★ Head - migraine, tension headache, cluster headache, cancer, cerebral aneurysm, sinusitis, meningitis
★ Neck pain - MI (atypical), trauma
★ Back - cancer, also see ''joints'' section
★ Breast - perimenstrual, cancer, trauma
★ Chest - MI (common and sometimes fatal), GERD (very common), pancreatitis, hiatal hernia, aortic dissection (rare), pulmonary embolism (more frequently asymptomatic), Costochondritis
★ Shoulder - cholecystitis (right side), MSK
★ Abdominal
★
★ Left and right upper quadrant - peptic ulcer disease, gastroenteritis, hepatitis, pancreatitis, cholecystitis, MI (atypical), abdominal aortic aneurysm, gastric cancer (usually asymptomatic)
★
★ Left and right lower quadrant - appendicitis (serious), ectopic pregnancy (serious/women only), endometriosis (women only), pelvic inflammatory disease (women only), diverticulitis (common in the elderly), urolithiasis, pyelonephritis, cancer (colorectal cancer most common)
★ Back - MSK (muscle strain), cancer, spinal disc herniation, degenerative disc disease, coccyx (coccydynia), also see ''joints'' section
★ Arm - myocardial infarction (classically the left arm, sometimes bilateral), musculoskeletal
★ Leg - deep vein thrombosis, peripheral vascular disease (claudication), musculoskeletal, spinal disc herniation, sciatica
★ Classically small joints - osteoarthritis (common in the elderly), rheumatoid arthritis, systemic lupus erythematosis, gout, pseudogout
★ Classically large joints (hip, knee) - osteoarthritis (common in the elderly), septic arthritis, hemarthrosis, osteonecrosis, trauma
★ Classically back - ankylosing spondylitis, inflammatory bowel disease
★ Other - psoriatic arthritis, Reiter's syndrome
Pain refers to the subjective, unpleasant sensation that accompanies damage or near-damage to tissues, though it can also occur in the absence of such damage if the systems of nociception are not functioning properly. Nociception refers to the system that carries signals of damage and pain from the tissues; it is the physiological event that accompanies pain.[5]
Nociception is also known as ''nociperception'' or''physiological pain'' and is distinct from psychological pain.
All nociceptors are free nerve endings that have their cell bodies outside the spinal column in the dorsal root ganglion and are named based upon their appearance at their sensory ends. Nociceptors can detect mechanical, thermal, and chemical stimuli, and are found in the skin and on internal surfaces such as the periosteum or joint surfaces. Deep internal surfaces are only weakly supplied with pain receptors and will propagate sensations of chronic, aching pain if tissue damage in these areas occurs.
Nociceptors do not adapt to stimulus. In some conditions, excitation of pain fibers becomes greater as the pain stimulus continues, leading to a condition called hyperalgesia.
There are two ways for nociceptive information to reach the central nervous system, the neospinothalamic tract for 'fast pain' and the paleospinothalamic tract for 'slow pain'.
Fast pain travels via type Aδ fibers to terminate on the dorsal horn of the spinal cord where they synapse with the dendrites of the neospinothalamic tract. The axons of these neurons travel up the spine to the brain and cross the midline through the anterior white commissure, passing upwards in the contralateral anterolateral columns. These fibres terminate on the ventrobasal complex of the thalamus and synapse with the dendrites of the somatosensory cortex. Fast pain is felt within a tenth of a second of application of the pain stimulus and is a sharp, acute, prickling pain felt in response to mechanical and thermal stimulation. It can be localised easily if Aδ fibres are stimulated together with tactile receptors.
Slow pain is transmitted via slower type C fibers to laminae II and III of the dorsal horns, together known as the substantia gelatinosa. Impulses are then transmitted to nerve fibers that terminate in lamina V, also in the dorsal horn, synapsing with neurons that join fibers from the fast pathway, crossing to the opposite side via the anterior white commissure, and traveling upwards through the anterolateral pathway. These neurons terminate throughout in the brain stem, with one tenth of fibres stopping in the thalamus, and the rest stopping in the medulla, pons and periaqueductal grey of the midbrain tectum. Slow pain is stimulated by chemical stimulation, is poorly localized and is described as an aching, throbbing or burning pain.
When the nociceptors are stimulated they transmit signals through sensory neurons in the spinal cord. These neurons release the exicitory neurotransmitter glutamate at their synapses.
If the signals are sent to the reticular formation and thalamus, the sensation of pain enters consciousness in a dull poorly localised manner. From the thalamus, the signal can travel to the somatosensory cortex in the cerebrum, when the pain is experienced as localised and having more specific qualities.
Nociception can also cause generalized autonomic responses before or without reaching consciousness to cause pallor, diaphoresis, bradycardia, hypotension, lightheadedness, nausea and fainting.[6]
The body possesses an endogenous analgesia system, which can be supplemented with analgesic drugs to regulate nociception and pain. There is both an analgesia system in the central nervous system and peripheral receptors that decreases the grade in which pain reaches the higher brain areas. The perception of pain can be modified by the body according to gate control theory of pain.
The 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.
Main articles: Gate control theory of pain
The gate control theory of pain, proposed by Patrick Wall and Ron Melzack, postulates that nociception (pain) is "gated" by non-nociception 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 nociception (pain) information.
Pain may be experienced differently depending on phenotype. A study by Liem ''et al.'' suggests that redheads are more susceptible to thermal pain.[7]
Gene SCN9A 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. People having this disorder are completely ignorant to pain, and can perform without pain any kinds of self mutilation or damage. In the families studied, this has ranged from biting of the person's own tongue leading to damage, through to street acts with knives, to death from injuries due to a failure to have learned limits on injury through experience of pain. The same gene also appears to mediate a form of ''hyper-sensitivity'' to pain, with other mutations seeming to be "at the root of paroxysmal extreme pain disorder" according to a 2006 report in ''Neurone''. Various other forms of somatic sensitivity are unaffected.[8]
A recent survey by NCCAM (part of the NIH) found pain was the most common reason that people use alternative medicine. Among American adults who used CAM in 2002, 16.8% used CAM to treat back pain; 6.6% for neck pain; 4.9% for arthritis; 4.9% for joint pain; 3.1% for headache; and 2.4% used CAM to treat recurring pain. (Some survey respondents may have used CAM to treat more than one of these pain conditions.)
One such alternative, traditional Chinese medicine, views pain as a qi "blockage" equivalent to electrical resistance, or as "stagnation of blood" – theorized as dehydration inhibiting metabolism. Traditional Chinese treatments such as acupuncture are said to be more effective for nontraumatic pain than traumatic pain. Although these claims have not found broad scientific acceptance, research into both the mechanism and clinical efficacy of acupuncture supports that it can have a role in pain reduction for both humans and animals. Although the mechanism is not fully understood, it is likely that acupuncture stimulates the release of large quantities of endogenous opioids.[9] A 2004 NCCAM-funded study showed that acupuncture provides pain relief and improved function in patients with osteoarthritis of the knee, causing some managed care organizations to support acupuncture as adjunctive therapy for this purpose.[10] The NIH's 1997 Consensus Statement on Acupunture notes that research has been mixed, partly due to difficulties with designing clinical studies with the proper controls.[11]
Another common alternative treatment for chronic pain is use of nutritional supplements such as:
★ Curcumin, a polyphenol found in turmeric (Curcuma Longa) and said to be a natural cox-2 inhibitor[12]
★ Glucosamine
★ Chondroitin
★ Bromelain (a digestive enzyme from pineapple core)
★ Omega-3 fatty acids.
The efficacy of Glucosamine and Chondroitin, popular supplements for patients with arthritis, were examinied in the GAIT study, a $12 million trial funded by the NIH which showed statistical evidence for the treatment's positive effect only amongst patients with moderate to severe pain, a small subsection of the study.[13]
Main articles: Pain (philosophy)
The concept of pain has played an important part in the study of philosophy, particularly in the philosophy of mind. The question of what pain actually consists in is still open since any evaluation is dependent upon what subject one approaches the question from. 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 (ie in the role it has in bringing about various effects) and nothing else. Some theologians and other spiritual traditions have much to say about the nature of pain and its various spiritual consequences, especially its role in growth, understanding, compassion, and in providing an aspect of life to be overcome.
Despite its unpleasantness, pain is an important part of the existence of humans and other animals; in fact, it is vital to survival. 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. People born with congenital insensitivity to pain usually have short life spans, and suffer numerous ailments such as broken bones, bed sores, and chronic infection.
The study of pain has in recent years diverged into many different fields from pharmacology to psychology and neurobiology. It was even proposed that fruit flies may be used as an animal model for pharmacological pain research.[14] Pain is also of interest in the search for the neural correlates of consciousness, as pain has many subjective psychological aspects besides the physiological nociception.
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 (pain receptors) is thought to be involved to some extent in producing headache pain. 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 doctors believe that psychogenic chronic pain exists as a protective distraction to keep dangerous repressed emotions such as anger or rage unconscious.[15] 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.
Pain is defined as a subjective conscious experience. The presence or absence of pain even in another human is only verifiable by their report; "Pain is whatever the experiencing person says it is, and exists whenever he says it does."[16] Currently, It is not scientifically possible to prove whether an animal is in pain or not.
To determine if an animal is likely to be able to experience pain, two tests are used.
★ The first is; does the animal respond to noxious stimulus? "Most, if not all, invertebrates have the capacity to detect and respond to noxious or aversive stimuli. That is, like vertebrates, they are capable of nociception".A Question of Pain in InvertebratesILAR Journal 33(1-2) 1991 retrieved 2007-01-06 Both vertebrates and non-vertebrates respond to noxious stimuli and are capable of modifying their response to such stimuli. However noxious stimuli will cause complex, though automatic, responses in animals who have had the higher regions of their brains destroyed and are thus incapable of experiencing pain. Which leads to;
★ the second question; does noxious stimulus have longer lasting effects that indicate that pain has been experienced. If pain was experienced, the animal would "guard" an injured part of his body and show aggression when approached. There would also be a decrease in movement, feeding or sexual activity. Also, the reasoning behind this question is that the likely evolutionary benefit of experiencing pain is that learning to withdraw from the noxious stimulus, and avoid similar situations in future, is enhanced and therefore the animal is more likely to survive and breed. From this line of reasoning, if no learning from noxious stimulus is seen, then pain was not experienced. In fact, as pain is useful to shape behaviour, it seems unlikely to occur in species whose behaviour is genetically programmed and inherited.
From these lines of questioning the following groups have been identified;
★ Most invertebrates — including lobsters, crabs, worms, snails, slugs and clams- reaction to noxious stimulus does occur but no reports of longer term learning from pain — probably don't have the capacity to feel pain.[17]
★ Insects; possibly don't experience pain. Sometimes no response to noxious stimulus. No sign of longer term avoidance. Possibly do not feel pain.
★ Cephalopods (octopus, squid); long term withdrawal from possibly painful stimuli observed - possibly do experience pain.
★ Fish; respond to noxious stimuli - reports of long term learning from noxious stimulus - possibly do experience pain.[18]
★ Other non-human vertebrates (mammals, birds and reptiles); vocalizations and physiological responses (e.g. the release of stress hormones) are similar to our own when we are in pain, learned long term avoidance from noxious stimulus observed - suggesting these animals do experience pain.[19]
In veterinary science this uncertainty is overcome by assuming that if something would be painful for a human then it would be painful for an animal.[20] Where possible, analgesics are used preemptively if there is any likelihood of pain being caused to an animal.
★ Dolorimeter
★ Chronic pain
★ Pain disorder
★ Pain management
★ Pain scale
★ Neuropathy
★ Agony
★ Nociceptor
★ Allodynia
★ Hyperalgesia
★ International Association for the Study of Pain
1. IASP Pain Terminology
2. ''The American Heritage Stedman's Medical Dictionary'', 2nd Edition, Houghton Mifflin, 2004. Cited online at medical-dictionary.thefreedictionary.com.
3. Sarno, John E., MD, et. al., ''The Divided Mind: The Epidemic of Mindbody Disorders'' 2006 (ISBN 0-06-085178-3)
4. Pre-emptive analgesia, Dahl JB, Moiniche S, , , Br Med Bull, 2004
5. "Assessing Pain and Distress: A Veterinary Behaviorist's Perspective by Kathryn Bayne" in "Definition of Pain and Distress and Reporting Requirements for Laboratory Animals: Proceedings of the Workshop Held June 22, 2000 (2000)
6. cite seen at 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 retrieved 2007-01-06
7. Liem EB, Joiner TV, Tsueda K, Sessler DI. Increased sensitivity to thermal pain and reduced subcutaneous lidocaine efficacy in redheads. ''Anesthesiology.'' 2005 Mar;102(3):509-14.
8. http://www.nature.com/news/2006/061211/full/061211-11.html
9. Robert Sapolsky, ''Why zebras don't get ulcers'', pp 196-197: "Scientists noted that Chinese veterinarians used acupuncture to do surgery on animals, thereby refuting the argument that the painkilling characteristics of acupuncture was one big placebo effect ascribable to cultural conditioning (no cow on earth will go along with unanaesthetized surgery just because it has a heavy investment in the cultural mores of the society in which it dwells. [...] Acupuncture stimulates the release of large quantities of endogenous opioids, for reasons no one really understands. The best demonstration of this is what is called a subtraction experiment: block the activity of endogenous opioids by using a drug that blocks the opiate receptor... acupuncture no longer effectively dulls the perception of pain."
10. Berman BM, Lao L, Langenberg P, Lee WL, Gilpin AM, Hochberg MC. "Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee: a randomized, controlled trial." ''Annals of Internal Medicine'' 2004 Dec 21; 141(12): 901-10.
11. National Institutes of Health Consensus Panel. "Acupuncture: National Institutes of Health Consensus Development Statement." National Institutes of Health Web site. Accessed at consensus.nih.gov/1997/1997Acupuncture107html.htm on February 24, 2007.
12. Sharma S, Kulkarni SK, Agrewala JN, Chopra K. "Curcumin attenuates thermal hyperalgesia in a diabetic mouse model of neuropathic pain." Eur J Pharmacol. 2006 May 1; 536(3): 256-61
13. Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, Bradley JD, Bingham CO, Weisman MH, Jackson CG, Lane NE, Cush JJ, Moreland LW, Schumacher HR, Oddis CV, Wolfe F, Molitor JA, Yocum DE, Schnitzer TJ, Furst DE, Sawitzke AD, Shi H, Brandt KD, Moskowitz RW, Williams HJ. "Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis." ''New England Journal of Medicine''. 2006 Feb 23; 354(8): 795-808.
14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15763072&query_hl=21
15. Sarno, John E., MD, et. al., ''The Divided Mind: The Epidemic of Mindbody Disorders'' 2006 (ISBN 0-06-085178-3) pp.61-65.
16. cite sourced from McCaffery M. Nursing management of the patient in pain. Philadelphia, Pa: JB Lippincott 1972.
17. cbsnewsHot Debate: Do Lobsters Feel Pain? Feb. 14, 2005 retrieved 2007-01-06
18. Report prepared for the RSPCA by S.C. Kestin 2004 36 p. Amended. NAL Call no: SH177.S75K47 Pain and Stress in Fish. April 1994. retrieved 2007-01-29
19. The Senate Standing Committee on Legal and Constitutional Affairs Do Invertebrates Feel Pain? retrieved 2007-01-06
20. American College of Veterinary Anesthesiologists' position paper on the treatment of pain in animals retrieved 2007-01-06
★ American Pain Society
★ American Pain Foundation
★ American Academy of Pain Management
★ American Academy of Pain Medicine
★ Society for Pain Practice Management
★ American Board of Pain Medicine
★ Pain Management Information: includes conventional & alternative treatments.
★ Institute for Pain Diagnostic
★ Help Roberto: The website of a young boy who cannot feel any pain
★ Human Pain Research Group, University of Manchester
★ Pain Map PDF from Nature.com
★ , prepared for the Workers' Compensation Board of Nova Scotia
'Pain' is an unpleasant sensation. It 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”.
'Nociception'[1] (sometimes also called ''nociperception''[2]) is a measurable physiological event of a type usually associated with pain.
Scientifically, ''pain'' (a subjective experience) is separate and distinct from ''nociception'', the system which carries information about inflammation, damage or near-damage in tissue, to the spinal cord and brain. Nociception frequently occurs without pain being felt and can convey information without conscious awareness. Conversely, but less frequently, a sensation of pain can exist in the absence of nociception.
Pain is part of the body's defense system: it triggers mental problem-solving strategies that seek to end the painful experience, and it promotes learning, making repetition of the painful situation less likely. The nociceptive system transmits signals that usually trigger the sensation of pain, it is a critical component of the body's ability to react to damaging stimuli and it is part of a rapid-warning relay instructing the central nervous system to initiate reactions for minimizing injury.
Description
Intensity
Pain may range in intensity from slight through severe to agonizing. It is experienced as having qualities such as sharp, throbbing, dull, nauseating, burning and shooting. It often has both an emotional quality and a sensed bodily location. Medical professionals will sometimes ask patients to rate their pain on a scale of zero through ten, where ten is consistent with screaming and thrashing about.
Localisation
This subjective reality of the localisation of pain to an area of the body is the basis for speaking of ''pain receptor, neck pain, referred pain, cutaneous pain,'' as well as ''pain in my foot'', ''kidney pain,'' or the ''painful uterine contractions'' occurring during childbirth. This common usage of ''pain'' is not entirely consistent with the scientists' model of pain being a subjective experience.
Insensitivity to pain
Inability to experience pain, as in the rare condition congenital insensitivity to pain or congenital analgesia, can cause various health problems.
Types of pain
Pain can be classified as ''acute'' or ''chronic.'' The distinction between acute and chronic pain is not based on its duration of sensation, but rather the nature of the pain itself. In general, physicians are more comfortable treating acute pain, which has as its source soft tissue damage, infection and/or inflammation. It can be modulated and removed by treating its cause and through combined strategies using analgesics to treat the pain and antibiotics to treat the infection. In general, while it is uncomfortable to experience, it is easy to treat; is distinguished by having a specific cause and purpose, and generally produces no persistent psychological reaction. Physicians are more likely to prescribe medications to treat acute pain, particularly in those situations when they are satisfied that they understand the pain's origin and believe the pain will be short in duration. This is why a patient might leave the hospital with two weeks' worth of adequate pain medicine, but the same medications may not be readily prescribed if the patient's pain lasts beyond an expected period of time. It is not the pain itself that is short in duration: it is the diagnosis of "acute pain" and the expectation that it will be short in nature that continues to confuse both the medical establishment and those who experience pain.
The primary distinction is this: acute pain serves to protect one after an injury. Chronic pain does not serve this or any other purpose. Acute pain is the symptom of pain. Chronic pain is the disease of pain.
Chronic Pain
American pain associations estimate that 40-80 million Americans live with chronic pain. At the same time, there are only 8,000 qualified pain management specialists. Many physicians faced with patients who live with chronic pain have had no professional training in pain management. It is not regularly taught in medical school, and even recent legislation in some states to ensure that physicians receive continuing education in pain medicine and end-of-life care do not guarantee proper training in pain. In many states, there remains no legislation ensuring that licensed physicians, even those who work in hospital emergency rooms, have any pain management training whatsoever.
Chronic pain has no time limit, often has no apparent cause and serves no apparent biological purpose. Chronic pain can trigger multiple psychological problems that confound both patient and health care provider, leading to feelings of helplessness and hopelessness. The most common causes of chronic pain include low-back pain, headache, recurrent facial pain, cancer pain, and arthritic pain. Sometimes chronic pain can have a psychosomatic or psychogenic cause.[3]
Chronic pain was originally defined as pain that has lasted 6 months or longer. It is now defined as "the disease of pain." Its origin, duration, intensity, and specific symptoms vary. The one consistent fact of chronic pain is that, as a disease, it cannot be understood in the same terms as acute pain, and the failure to make this distinction (particularly in those who suffer chronic pain) has been and continues to be the cause of multi-dimensional suffering, depression, social isolation, and helplessness. The failure to recognize chronic pain as substantially different from acute pain cannot be blamed on the medical profession: it is a societal lapse.
Chronic pain, no matter how debilitating it is in one's life, continues to be considered by most insurance carriers as a 3-17% disability.
There have been some theories that not treating acute pain properly can lead to chronic pain.[4]
The experience of physiological pain can be grouped according to the source and related nociceptors (pain-detecting neurons).
★ '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 well-defined, localized pain of short duration. Examples of injuries that produce cutaneous pain include paper cuts, minor cuts, minor (first degree) burns and lacerations.
★ 'Somatic pain' originates from ligaments, tendons, bones, blood vessels, and even nerves themselves. It is detected with somatic nociceptors. The scarcity of pain receptors in these areas produces a dull, poorly-localized pain of longer duration than cutaneous pain; examples include sprains and broken bones. Myofascial pain usually is caused by trigger points in muscles, tendons and fascia, and may be local or referred.
★ '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 and of a longer duration than somatic pain. Visceral pain 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. Myocardial ischaemia (the loss of blood flow to a part of the heart muscle tissue) is possibly the best known example of referred pain; the sensation can occur in the upper chest as a restricted feeling, or as an ache in the left shoulder, arm or even hand. "The brain freeze" is another example of referred pain, in which the vagus nerve is cooled by cold inside the throat. Referred pain can be explained by the findings that pain receptors in the viscera also excite spinal cord neurons that are excited by cutaneous tissue. Since the brain normally associates firing of these spinal cord neurons with stimulation of somatic tissues in skin or muscle, pain signals arising from the viscera are interpreted by the brain as originating from the skin. The theory that visceral and somatic pain receptors converge and form synapses on the same spinal cord pain-transmitting neurons is called "Ruch's Hypothesis".
★ 'Phantom limb pain', a type of referred 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.
★ 'Neuropathic pain', can occur as a result of injury or disease to the nerve tissue itself. This can disrupt the ability of the sensory nerves to transmit correct information to the thalamus, and hence the brain interprets painful stimuli even though there is no obvious or known physiologic cause for the pain. Neuropathic pain is, as stated above, the disease of pain. It is not the sole definition for chronic pain, but does meet its criteria.
Selected common and serious causes of pain by region
Visceral pain sensation is often referred by the CNS to a dermatome region which may be far away from the originating organ. These correlate to the position of the organ in the embryo. Examples of this include the heart which originates in the neck, thus producing the classical pain and arm pain experienced during acute cardiac pain.
Head and neck
★ Jaw - Temporal arteritis (serious), trauma
★ Ear - otitis media (very common esp. in children), otitis externa, trauma
★ Eye - glaucoma, trauma
★ Head - migraine, tension headache, cluster headache, cancer, cerebral aneurysm, sinusitis, meningitis
★ Neck pain - MI (atypical), trauma
Thorax
★ Back - cancer, also see ''joints'' section
★ Breast - perimenstrual, cancer, trauma
★ Chest - MI (common and sometimes fatal), GERD (very common), pancreatitis, hiatal hernia, aortic dissection (rare), pulmonary embolism (more frequently asymptomatic), Costochondritis
★ Shoulder - cholecystitis (right side), MSK
Abdomen
★ Abdominal
★
★ Left and right upper quadrant - peptic ulcer disease, gastroenteritis, hepatitis, pancreatitis, cholecystitis, MI (atypical), abdominal aortic aneurysm, gastric cancer (usually asymptomatic)
★
★ Left and right lower quadrant - appendicitis (serious), ectopic pregnancy (serious/women only), endometriosis (women only), pelvic inflammatory disease (women only), diverticulitis (common in the elderly), urolithiasis, pyelonephritis, cancer (colorectal cancer most common)
Back
★ Back - MSK (muscle strain), cancer, spinal disc herniation, degenerative disc disease, coccyx (coccydynia), also see ''joints'' section
Limbs
★ Arm - myocardial infarction (classically the left arm, sometimes bilateral), musculoskeletal
★ Leg - deep vein thrombosis, peripheral vascular disease (claudication), musculoskeletal, spinal disc herniation, sciatica
Joints
★ Classically small joints - osteoarthritis (common in the elderly), rheumatoid arthritis, systemic lupus erythematosis, gout, pseudogout
★ Classically large joints (hip, knee) - osteoarthritis (common in the elderly), septic arthritis, hemarthrosis, osteonecrosis, trauma
★ Classically back - ankylosing spondylitis, inflammatory bowel disease
★ Other - psoriatic arthritis, Reiter's syndrome
Physiology of nociception
Pain refers to the subjective, unpleasant sensation that accompanies damage or near-damage to tissues, though it can also occur in the absence of such damage if the systems of nociception are not functioning properly. Nociception refers to the system that carries signals of damage and pain from the tissues; it is the physiological event that accompanies pain.[5]
Nociception is also known as ''nociperception'' or''physiological pain'' and is distinct from psychological pain.
Nociceptors
All nociceptors are free nerve endings that have their cell bodies outside the spinal column in the dorsal root ganglion and are named based upon their appearance at their sensory ends. Nociceptors can detect mechanical, thermal, and chemical stimuli, and are found in the skin and on internal surfaces such as the periosteum or joint surfaces. Deep internal surfaces are only weakly supplied with pain receptors and will propagate sensations of chronic, aching pain if tissue damage in these areas occurs.
Nociceptors do not adapt to stimulus. In some conditions, excitation of pain fibers becomes greater as the pain stimulus continues, leading to a condition called hyperalgesia.
Transmission of nociception to the central nervous system
There are two ways for nociceptive information to reach the central nervous system, the neospinothalamic tract for 'fast pain' and the paleospinothalamic tract for 'slow pain'.
Neospinothalamic tract
Fast pain travels via type Aδ fibers to terminate on the dorsal horn of the spinal cord where they synapse with the dendrites of the neospinothalamic tract. The axons of these neurons travel up the spine to the brain and cross the midline through the anterior white commissure, passing upwards in the contralateral anterolateral columns. These fibres terminate on the ventrobasal complex of the thalamus and synapse with the dendrites of the somatosensory cortex. Fast pain is felt within a tenth of a second of application of the pain stimulus and is a sharp, acute, prickling pain felt in response to mechanical and thermal stimulation. It can be localised easily if Aδ fibres are stimulated together with tactile receptors.
Paleospinothalamic tract
Slow pain is transmitted via slower type C fibers to laminae II and III of the dorsal horns, together known as the substantia gelatinosa. Impulses are then transmitted to nerve fibers that terminate in lamina V, also in the dorsal horn, synapsing with neurons that join fibers from the fast pathway, crossing to the opposite side via the anterior white commissure, and traveling upwards through the anterolateral pathway. These neurons terminate throughout in the brain stem, with one tenth of fibres stopping in the thalamus, and the rest stopping in the medulla, pons and periaqueductal grey of the midbrain tectum. Slow pain is stimulated by chemical stimulation, is poorly localized and is described as an aching, throbbing or burning pain.
Effects in CNS
When the nociceptors are stimulated they transmit signals through sensory neurons in the spinal cord. These neurons release the exicitory neurotransmitter glutamate at their synapses.
If the signals are sent to the reticular formation and thalamus, the sensation of pain enters consciousness in a dull poorly localised manner. From the thalamus, the signal can travel to the somatosensory cortex in the cerebrum, when the pain is experienced as localised and having more specific qualities.
Nociception can also cause generalized autonomic responses before or without reaching consciousness to cause pallor, diaphoresis, bradycardia, hypotension, lightheadedness, nausea and fainting.[6]
Analgesia
The body possesses an endogenous analgesia system, which can be supplemented with analgesic drugs to regulate nociception and pain. There is both an analgesia system in the central nervous system and peripheral receptors that decreases the grade in which pain reaches the higher brain areas. The perception of pain can be modified by the body according to gate control theory of pain.
Central
The 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.
Peripheral
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.
Factors
Main articles: Gate control theory of pain
The gate control theory of pain, proposed by Patrick Wall and Ron Melzack, postulates that nociception (pain) is "gated" by non-nociception 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 nociception (pain) information.
Phenotype and pain
Pain may be experienced differently depending on phenotype. A study by Liem ''et al.'' suggests that redheads are more susceptible to thermal pain.[7]
Gene SCN9A 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. People having this disorder are completely ignorant to pain, and can perform without pain any kinds of self mutilation or damage. In the families studied, this has ranged from biting of the person's own tongue leading to damage, through to street acts with knives, to death from injuries due to a failure to have learned limits on injury through experience of pain. The same gene also appears to mediate a form of ''hyper-sensitivity'' to pain, with other mutations seeming to be "at the root of paroxysmal extreme pain disorder" according to a 2006 report in ''Neurone''. Various other forms of somatic sensitivity are unaffected.[8]
Pain and alternative medicine
A recent survey by NCCAM (part of the NIH) found pain was the most common reason that people use alternative medicine. Among American adults who used CAM in 2002, 16.8% used CAM to treat back pain; 6.6% for neck pain; 4.9% for arthritis; 4.9% for joint pain; 3.1% for headache; and 2.4% used CAM to treat recurring pain. (Some survey respondents may have used CAM to treat more than one of these pain conditions.)
One such alternative, traditional Chinese medicine, views pain as a qi "blockage" equivalent to electrical resistance, or as "stagnation of blood" – theorized as dehydration inhibiting metabolism. Traditional Chinese treatments such as acupuncture are said to be more effective for nontraumatic pain than traumatic pain. Although these claims have not found broad scientific acceptance, research into both the mechanism and clinical efficacy of acupuncture supports that it can have a role in pain reduction for both humans and animals. Although the mechanism is not fully understood, it is likely that acupuncture stimulates the release of large quantities of endogenous opioids.[9] A 2004 NCCAM-funded study showed that acupuncture provides pain relief and improved function in patients with osteoarthritis of the knee, causing some managed care organizations to support acupuncture as adjunctive therapy for this purpose.[10] The NIH's 1997 Consensus Statement on Acupunture notes that research has been mixed, partly due to difficulties with designing clinical studies with the proper controls.[11]
Another common alternative treatment for chronic pain is use of nutritional supplements such as:
★ Curcumin, a polyphenol found in turmeric (Curcuma Longa) and said to be a natural cox-2 inhibitor[12]
★ Glucosamine
★ Chondroitin
★ Bromelain (a digestive enzyme from pineapple core)
★ Omega-3 fatty acids.
The efficacy of Glucosamine and Chondroitin, popular supplements for patients with arthritis, were examinied in the GAIT study, a $12 million trial funded by the NIH which showed statistical evidence for the treatment's positive effect only amongst patients with moderate to severe pain, a small subsection of the study.[13]
Philosophy of pain
Main articles: Pain (philosophy)
The concept of pain has played an important part in the study of philosophy, particularly in the philosophy of mind. The question of what pain actually consists in is still open since any evaluation is dependent upon what subject one approaches the question from. 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 (ie in the role it has in bringing about various effects) and nothing else. Some theologians and other spiritual traditions have much to say about the nature of pain and its various spiritual consequences, especially its role in growth, understanding, compassion, and in providing an aspect of life to be overcome.
Survival benefit
Despite its unpleasantness, pain is an important part of the existence of humans and other animals; in fact, it is vital to survival. 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. People born with congenital insensitivity to pain usually have short life spans, and suffer numerous ailments such as broken bones, bed sores, and chronic infection.
The study of pain has in recent years diverged into many different fields from pharmacology to psychology and neurobiology. It was even proposed that fruit flies may be used as an animal model for pharmacological pain research.[14] Pain is also of interest in the search for the neural correlates of consciousness, as pain has many subjective psychological aspects besides the physiological nociception.
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 (pain receptors) is thought to be involved to some extent in producing headache pain. 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 doctors believe that psychogenic chronic pain exists as a protective distraction to keep dangerous repressed emotions such as anger or rage unconscious.[15] 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.
Pain and nociception in other species
Pain is defined as a subjective conscious experience. The presence or absence of pain even in another human is only verifiable by their report; "Pain is whatever the experiencing person says it is, and exists whenever he says it does."[16] Currently, It is not scientifically possible to prove whether an animal is in pain or not.
To determine if an animal is likely to be able to experience pain, two tests are used.
★ The first is; does the animal respond to noxious stimulus? "Most, if not all, invertebrates have the capacity to detect and respond to noxious or aversive stimuli. That is, like vertebrates, they are capable of nociception".A Question of Pain in InvertebratesILAR Journal 33(1-2) 1991 retrieved 2007-01-06 Both vertebrates and non-vertebrates respond to noxious stimuli and are capable of modifying their response to such stimuli. However noxious stimuli will cause complex, though automatic, responses in animals who have had the higher regions of their brains destroyed and are thus incapable of experiencing pain. Which leads to;
★ the second question; does noxious stimulus have longer lasting effects that indicate that pain has been experienced. If pain was experienced, the animal would "guard" an injured part of his body and show aggression when approached. There would also be a decrease in movement, feeding or sexual activity. Also, the reasoning behind this question is that the likely evolutionary benefit of experiencing pain is that learning to withdraw from the noxious stimulus, and avoid similar situations in future, is enhanced and therefore the animal is more likely to survive and breed. From this line of reasoning, if no learning from noxious stimulus is seen, then pain was not experienced. In fact, as pain is useful to shape behaviour, it seems unlikely to occur in species whose behaviour is genetically programmed and inherited.
From these lines of questioning the following groups have been identified;
★ Most invertebrates — including lobsters, crabs, worms, snails, slugs and clams- reaction to noxious stimulus does occur but no reports of longer term learning from pain — probably don't have the capacity to feel pain.[17]
★ Insects; possibly don't experience pain. Sometimes no response to noxious stimulus. No sign of longer term avoidance. Possibly do not feel pain.
★ Cephalopods (octopus, squid); long term withdrawal from possibly painful stimuli observed - possibly do experience pain.
★ Fish; respond to noxious stimuli - reports of long term learning from noxious stimulus - possibly do experience pain.[18]
★ Other non-human vertebrates (mammals, birds and reptiles); vocalizations and physiological responses (e.g. the release of stress hormones) are similar to our own when we are in pain, learned long term avoidance from noxious stimulus observed - suggesting these animals do experience pain.[19]
In veterinary science this uncertainty is overcome by assuming that if something would be painful for a human then it would be painful for an animal.[20] Where possible, analgesics are used preemptively if there is any likelihood of pain being caused to an animal.
See also
★ Dolorimeter
★ Chronic pain
★ Pain disorder
★ Pain management
★ Pain scale
★ Neuropathy
★ Agony
★ Nociceptor
★ Allodynia
★ Hyperalgesia
★ International Association for the Study of Pain
References
1. IASP Pain Terminology
2. ''The American Heritage Stedman's Medical Dictionary'', 2nd Edition, Houghton Mifflin, 2004. Cited online at medical-dictionary.thefreedictionary.com.
3. Sarno, John E., MD, et. al., ''The Divided Mind: The Epidemic of Mindbody Disorders'' 2006 (ISBN 0-06-085178-3)
4. Pre-emptive analgesia, Dahl JB, Moiniche S, , , Br Med Bull, 2004
5. "Assessing Pain and Distress: A Veterinary Behaviorist's Perspective by Kathryn Bayne" in "Definition of Pain and Distress and Reporting Requirements for Laboratory Animals: Proceedings of the Workshop Held June 22, 2000 (2000)
6. cite seen at 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 retrieved 2007-01-06
7. Liem EB, Joiner TV, Tsueda K, Sessler DI. Increased sensitivity to thermal pain and reduced subcutaneous lidocaine efficacy in redheads. ''Anesthesiology.'' 2005 Mar;102(3):509-14.
8. http://www.nature.com/news/2006/061211/full/061211-11.html
9. Robert Sapolsky, ''Why zebras don't get ulcers'', pp 196-197: "Scientists noted that Chinese veterinarians used acupuncture to do surgery on animals, thereby refuting the argument that the painkilling characteristics of acupuncture was one big placebo effect ascribable to cultural conditioning (no cow on earth will go along with unanaesthetized surgery just because it has a heavy investment in the cultural mores of the society in which it dwells. [...] Acupuncture stimulates the release of large quantities of endogenous opioids, for reasons no one really understands. The best demonstration of this is what is called a subtraction experiment: block the activity of endogenous opioids by using a drug that blocks the opiate receptor... acupuncture no longer effectively dulls the perception of pain."
10. Berman BM, Lao L, Langenberg P, Lee WL, Gilpin AM, Hochberg MC. "Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee: a randomized, controlled trial." ''Annals of Internal Medicine'' 2004 Dec 21; 141(12): 901-10.
11. National Institutes of Health Consensus Panel. "Acupuncture: National Institutes of Health Consensus Development Statement." National Institutes of Health Web site. Accessed at consensus.nih.gov/1997/1997Acupuncture107html.htm on February 24, 2007.
12. Sharma S, Kulkarni SK, Agrewala JN, Chopra K. "Curcumin attenuates thermal hyperalgesia in a diabetic mouse model of neuropathic pain." Eur J Pharmacol. 2006 May 1; 536(3): 256-61
13. Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, Bradley JD, Bingham CO, Weisman MH, Jackson CG, Lane NE, Cush JJ, Moreland LW, Schumacher HR, Oddis CV, Wolfe F, Molitor JA, Yocum DE, Schnitzer TJ, Furst DE, Sawitzke AD, Shi H, Brandt KD, Moskowitz RW, Williams HJ. "Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis." ''New England Journal of Medicine''. 2006 Feb 23; 354(8): 795-808.
14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15763072&query_hl=21
15. Sarno, John E., MD, et. al., ''The Divided Mind: The Epidemic of Mindbody Disorders'' 2006 (ISBN 0-06-085178-3) pp.61-65.
16. cite sourced from McCaffery M. Nursing management of the patient in pain. Philadelphia, Pa: JB Lippincott 1972.
17. cbsnewsHot Debate: Do Lobsters Feel Pain? Feb. 14, 2005 retrieved 2007-01-06
18. Report prepared for the RSPCA by S.C. Kestin 2004 36 p. Amended. NAL Call no: SH177.S75K47 Pain and Stress in Fish. April 1994. retrieved 2007-01-29
19. The Senate Standing Committee on Legal and Constitutional Affairs Do Invertebrates Feel Pain? retrieved 2007-01-06
20. American College of Veterinary Anesthesiologists' position paper on the treatment of pain in animals retrieved 2007-01-06
External links
★ American Pain Society
★ American Pain Foundation
★ American Academy of Pain Management
★ American Academy of Pain Medicine
★ Society for Pain Practice Management
★ American Board of Pain Medicine
★ Pain Management Information: includes conventional & alternative treatments.
★ Institute for Pain Diagnostic
★ Help Roberto: The website of a young boy who cannot feel any pain
★ Human Pain Research Group, University of Manchester
★ Pain Map PDF from Nature.com
★ , prepared for the Workers' Compensation Board of Nova Scotia
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