Pain and nociception

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Pain is an unpleasant sensation; nociception or nociperception is a measurable physiological event of a type usually associated with pain. A sensation of pain can exist in the absence of nociception: it can occur in response to both external perceived events—for example, seeing something—or internal cognitive events—for example, the phantom limb pain of a amputee.

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. In plain words: when you experience pain, you feel badly and your body hurts somewhere.

This subjective reality of the localization 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.

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 is below the level of consciousness. Despite it triggering pain and suffering, nociception is a critical component of the body's defense system. It is part of a rapid warning relay instructing the central nervous system to initiate motor neurons in order to minimize detected physical harm.

Inability to experience pain, as in the rare condition congenital insensitivity to pain or congenital analgesia, can cause various health problems. The two most common forms of pain reported in the United States are headache and back pain.

The word "pain" comes from the Latin: poena

meaning punishment, a fine, a penalty.

Types of pain

Pain can be classified as acute or chronic.

• Acute pain is defined as short-term but extreme pain that comes on quickly but last only for a brief period of time. Acute pain is the body's warning of present damage to tissue or disease. It is often fast and sharp followed by aching pain. Acute pain is centralized in one area before becoming somewhat spread out. This type of pain responds well to medications.

• Chronic pain was originally defined as pain that has lasted 6 months or longer. It is now defined as pain that persists longer than the normal course of time associated with a particular type of injury. This constant or intermittent pain has often outlived its purpose, as it does not help the body to prevent injury. It is often more difficult to treat than acute pain. Expert care is generally necessary to treat any pain that has become chronic, and coordinated treatment from an interdisciplinary health care team, including medical physicians, physical therapists, and psychologists or psychiatrists, often beneficial. An anterior cingulectomy, neurosurgery that disconnects the anterior cingulate gyrus, can be used in extreme cases to treat chronic pain. Post-surgery the patient will still feel the sensation of pain, but not the accompanying emotion. There have been some theories that not treating acute pain properly can lead to chronic pain.

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.

• 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. 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 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, or "neuralgia", 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.

Selected common and serious causes of pain by region

It should be noted that 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.

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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 fatal), GERD (very common), pancreatitis, hiatal hernia, aortic dissection (rare), pulmonary embolism (more frequently asymptomatic), Costochondritis
• Shoulder - cholecystitis (right side), MSK

Abdomen

• Adominal
  • 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), pelvic inflammatory disease (women only), diverticulitis (common in old), urolithiasis (kidney stone), 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 - MI (classically left, sometimes bilateral), MSK
• Leg - deep vein thrombosis, peripheral vascular disease (claudication), MSK, spinal disc herniation, sciatica

Joints

• Classically small joints - osteoarthritis (common in old), rheumatoid arthritis, systemic lupus erythematosis, gout, pseudogout
• Classically large joints (hip, knee) - osteoarthritis (common in old), septic arthritis, hemarthrosis, trauma
• Classically back - ankylosing spondylitis, inflammatory bowel disease
• Other - psoriatic arthritis, Reiter's syndrome

Physiology of nociception (commonly Physiology of pain)

• This section, except in the paragraph on pain in consciousness, for historical reasons uses pain to refer to nociception. Where both a historical pain term and a modern nociception term are common, a bracketed pain term is included. e.g. Nociceptors (Pain receptors)

"Nociception is the term introduced almost 100 years ago by the great physiologist Sherrington (1906) to make clear the distinction between detection of a noxious event or a potentially harmful event and the psychological and other responses to it."

Nociception is the system which carries information about noxious stimilus, ussually associated with tissue damgage to the spinal cord and brain.

Nociception is also known as nociperception and physiological pain. Nociception is separate to, and distinct from, psychological pain.

Nociceptors (Pain receptors)

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. These sensory endings look like the branches of small bushes. There are mechanical, thermal, and chemical nociceptors. They are found in skin and on internal surfaces such as periosteum and 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.

Two main types of nociceptor, Aδ and C fibres, mediate fast and slow pain respectively. Thinly myelinated type Aδ fibres, which transmit signals at rates of between 6 to 30 meters per second mediate fast pain. This type of pain is felt within a tenth of a second of application of the pain stimulus. It can be described as sharp, acute, pricking pain and includes mechanical and thermal pain. Slow pain, mediated by slower, unmyelinated ("bare") type C pain fibers that send signals at rates between 0.5 and 2 meters per second, is an aching, throbbing, burning pain. Chemical pain is an example of slow pain. 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 (pain) signals in the central nervous system

There are 2 pathways for transmission of nociception in the central nervous system. These are the neospinothalamic tract (for fast pain) and the paleospinothalamic tract (for slow pain).

• Fast pain travels via type Aδ fibers to terminate on lamina I (lamina marginalis) of the dorsal horn of the spinal cord. Second order neurons of the neospinothalamic tract then take off and give rise to long fibres which cross the midline through the grey commisure and pass upwards in the contralateral anterolateral columns. These fibres then terminate on the reticular formation,Ventrobasal Complex (VBC) of the thalamus. From here, third order neurons communicate with the somatosensory cortex. Fast pain can be localised easily if Aδ fibres are stimulated together with tactile receptors.

• Slow pain is transmitted via slower type C fibres to laminae II and III of the dorsa horns, together known as the substantia gelatinosa. Second order neurons take off and terminate in lamina V, also in the dorsal horn. Third order neurons then join fibers from the fast pathway, crossing to the opposite side via the grey commisure, and traveling upwards through the anterolateral pathway. These neurons terminate widely in the brain stem, with one tenth of fibres stopping in the thalamus, and the rest stopping in the medulla, pons and tectum of midbrainmesencephalon, periaqueductal grey. Slow pain is poorly localized.

Consequences of nociception

When the nociceptors are stimulated they transmit signals through sensory neurons in the spinal cord. These neurons release glutamate, a major exicitory neurotransmitter that relays signals from one neuron to another.

If the signals are sent to the reticular formation of brain stem, thalamus, then pain enters consciousness, but in a dull porly 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.

Feinstein and colleagues found that nociception could also, "activate generalized autonomic responses independently of the relay of pain to conscious levels" causing "pallor, sweating, bradycardia, a drop in blood pressure, subjective "faintness," nausea and syncope" .

Analgesia

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.

The analgesia system is mediated by 3 major components : the periaquaductal grey matter (in the midbrain), the nucleus raphe magnus (in the medulla), and the nociception (pain) inhibitory neurons within the dorsal horns of the spinal cord, which act to inhibit nociception(pain)-transmitting neurons also located in the spinal dorsal horn.

The body has 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.

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 [1]. 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, is an exception to the idea that pain is helpful to survival. Furthermore, it is not clear what the survival benefit of sometimes 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.

Children and pain

Children have been proven to be markedly more sensitive to pain, but this fact is commonly dismissed as a fear reaction or a lack of coping abilities. Research has been carried out on how children can cope with pain due to increased sensitivity and it has been established that strategies that remove pain can help prevent long-term increases in sensitivity as the nervous system is still developing.

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.

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. [2]

Pain and alternative medicine

A recent survey by NCCAM found pain was the most common reason that people use complementary and alternative medicine (CAM). 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.

These claims have not been scientifically established, although research into acupuncture supports that it can have a role in pain reduction in both humans and animals, by stimulating the release of large quantities of endogenous opioids, although the mechanism is not yet fully understood.

Philosophy of pain

Main article: 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, dependent upon what subject one approaches the question from, an open one. 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. 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.

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.". 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 2 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".". Both vertebrates and non-vertebrates respond to noxious stimulii 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 expereincing pain. Which leads to;
• the second question; does noxious stimulus have longer lasting effects that indicate that pain has been experienced. 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.

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.
• Insects; possibly dont experience pain. Sometimes no response to noxious stimulus. No sign of longer term avoidance. Possible do not feel pain.
• Cephlapods (octopus, squid); long term withdrawal from possibly painful stimuli observed - possibly do experience pain.
• Fish; respond to noxious stimulus - no reports of long term learning from noxious stimulus - possibly do not experience pain.
• 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, learnt long term avoidance from noxious stimulus observed - suggesting these animals do experience pain .

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. Where possible analgesics are used premptively if there is any likelihood of pain being caused to an animal.

See also

Look up Pain in Wiktionary, the free dictionary.

• Suffering
• Masochism
• Pain management
• Congenital insensitivity to pain (Congenital analgesia)
• Headache
• Back pain
• Chronic pain
• Torture

References

• Guyton & Hall, (2005), Textbook of Medical Physiology (11th edition), Elsevier-Saunders

External links

• European Pain Network
• Laboratory of Elie D. Al-Chaer for the Study of Pain
• Sea Snails (Conus) harbour powerful new painkillers - the ACV1 snail polypeptide appears to be a potential analgesic
• The Society for Fighting Pain
• Fish capable of experiencing pain (rainbow trout may show pain responses, contrary to popular belief) - New Scientist 2003
• Developments in the neuroscience of pain
• Children and pain treatment
• National Headache Foundation
• Back pain and neck pain patient information

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