Pain and Nociception

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The word "pain" comes from the Latin: poena meaning punishment, a fine, a penalty. Pain is an unpleasant sensation; nociception or nociperception is a measurable physiological event of a type usually associated with pain and agony and suffering. 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 an amputee). Pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” - International Association for the Study of Pain (IASP). 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. Pain too 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 two most common forms of pain reported in the United States are headache and back pain.

Current Research

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For current research articles click - here

Description

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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.

Localization

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.

Insensitivity to Pain

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Inability to experience pain, as in the rare condition congenital insensitivity to pain or congenital analgesia, can cause various health problems.

Types of pain

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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. And sometimes chronic pain can have a psychosomatic or psychogenic cause.

Published information on pain perpetuate myths that do a disservice to those who live with pain and many glossaries contradict one another. One of the best studies, while slightly outdating and not answering all questions about chronic pain, was written by Dr. T.J. Murray of Dalhousie University.

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.

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

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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.

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), tension myositis syndrome, 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 erythematosus, 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 (Commonly Physiology of Pain)

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• 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, usually associated with tissue damage 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 fibres, 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 anterior white 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 dorsal 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 anterior white 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 midbrain mesencephalon, 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 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.

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.

Phenotype and Pain

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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.

Pain and Alternative Medicine

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A recent survey by NCCAM (part of the NIH) 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. 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. 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. 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.

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
• 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.

Philosophy of Pain

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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

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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. 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. And 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

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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, 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". 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 agression 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.
• 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.
• 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.

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 preemptively if there is any likelihood of pain being caused to an animal.


(adapted from Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Physical_pain)