Pain

Pain
ICD-10	R52
ICD-9	338
DiseasesDB	9503
MedlinePlus	002164
MeSH	D010146

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

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

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

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

Etymology

"Pain (n.) 1297, "punishment," especially for a crime; also (c.1300) "condition one feels when hurt, opposite of pleasure," from O.Fr. peine, from L. poena "punishment, penalty" (in L.L. also "torment, hardship, suffering"), from Gk. poine "punishment," from PIE *kwei- "to pay, atone, compensate" (...)."

A Brief History of Pain

Ancient civilizations recorded on stone tablets accounts of pain and the treatments used: pressure, heat, water, and sun. Early humans related pain to evil, magic, and demons. Relief of pain was the responsibility of sorcerers, shamans, priests, and priestesses, who used herbs, rites, and ceremonies as their treatments.

The Greeks and Romans were the first to advance a theory of sensation, the idea that the brain and nervous system have a role in producing the perception of pain. But it was not until the Middle Ages and well into the Renaissance-the 1400s and 1500s-that evidence began to accumulate in support of these theories. Leonardo da Vinci and his contemporaries came to believe that the brain was the central organ responsible for sensation. Da Vinci also developed the idea that the spinal cord transmits sensations to the brain.

In the 17th and 18th centuries, the study of the body-and the senses-continued to be a source of wonder for the world's philosophers. In 1664, the French philosopher René Descartes described what to this day is still called a "pain pathway." Descartes illustrated how particles of fire, in contact with the foot, travel to the brain and he compared pain sensation to the ringing of a bell.

In the 19th century, pain came to dwell under a new domain-science-paving the way for advances in pain therapy. Physician-scientists discovered that opium, morphine, codeine, and cocaine could be used to treat pain. These drugs led to the development of aspirin, to this day the most commonly used pain reliever. Before long, anesthesia-both general and regional-was refined and applied during surgery.

"It has no future but itself," wrote the 19th century American poet Emily Dickinson, speaking about pain. As the 21st century unfolds, however, advances in pain research are creating a less grim future than that portrayed in Dickinson’s verse, a future that includes a better understanding of pain, along with greatly improved treatments to keep it in check.

Overview of the Nervous Systems

The central nervous system (CNS) refers to the brain and spinal cord together. The peripheral nervous system refers to the cervical, thoracic, lumbar, and sacral nerve trunks leading away from the spine to the limbs. Messages related to function (such as movement) or dysfunction (such as pain) travel from the brain to the spinal cord and from there to other regions in the body and back to the brain again. The autonomic nervous system controls involuntary functions in the body, like perspiration, blood pressure, heart rate, or heart beat. It is divided into the sympathetic and parasympathetic nervous systems. The sympathetic and parasympathetic nervous systems have links to important organs and systems in the body; for example, the sympathetic nervous system controls the heart, blood vessels, and respiratory system, while the parasympathetic nervous system controls our ability to sleep, eat, and digest food.

The peripheral nervous system also includes 12 pairs of cranial nerves located on the underside of the brain. Most relay messages of a sensory nature. They include the olfactory (I), optic (II), oculomotor (III), trochlear (IV), trigeminal (V), abducens (VI), facial (VII), vestibulocochlear (VIII), glossopharyngeal (IX), vagus (X), accessory (XI), and hypoglossal (XII) nerves. Neuralgia, as in trigeminal neuralgia, is a term that refers to pain that arises from abnormal activity of a nerve trunk or its branches. The type and severity of pain associated with neuralgia vary widely.

A Pain Primer: What Do We Know About Pain?

We may experience pain as a prick, tingle, sting, burn, or ache. Receptors on the skin trigger a series of events, beginning with an electrical impulse that travels from the skin to the spinal cord. The spinal cord acts as a sort of relay center where the pain signal can be blocked, enhanced, or otherwise modified before it is relayed to the brain. One area of the spinal cord in particular, called the dorsal horn (see section on Spine Basics in the Appendix), is important in the reception of pain signals.

The most common destination in the brain for pain signals is the thalamus and from there to the cortex, the headquarters for complex thoughts. The thalamus also serves as the brain's storage area for images of the body and plays a key role in relaying messages between the brain and various parts of the body. In people who undergo an amputation, the representation of the amputated limb is stored in the thalamus. (For a discussion of the thalamus and its role in this phenomenon, called phantom pain, see section on Phantom Pain)

Pain is a complicated process that involves an intricate interplay between a number of important chemicals found naturally in the brain and spinal cord. In general, these chemicals, called neurotransmitters, transmit nerve impulses from one cell to another.

There are many different neurotransmitters in the human body; some play a role in human disease and, in the case of pain, act in various combinations to produce painful sensations in the body. Some chemicals govern mild pain sensations; others control intense or severe pain.

The body's chemicals act in the transmission of pain messages by stimulating neurotransmitter receptors found on the surface of cells; each receptor has a corresponding neurotransmitter. Receptors function much like gates or ports and enable pain messages to pass through and on to neighboring cells. One brain chemical of special interest to neuroscientists is glutamate. During experiments, mice with blocked glutamate receptors show a reduction in their responses to pain. Other important receptors in pain transmission are opiate-like receptors. Morphine and other opioid drugs work by locking on to these opioid receptors, switching on pain-inhibiting pathways or circuits, and thereby blocking pain.

Another type of receptor that responds to painful stimuli is called a nociceptor. Nociceptors are thin nerve fibers in the skin, muscle, and other body tissues, that, when stimulated, carry pain signals to the spinal cord and brain. Normally, nociceptors only respond to strong stimuli such as a pinch. However, when tissues become injured or inflamed, as with a sunburn or infection, they release chemicals that make nociceptors much more sensitive and cause them to transmit pain signals in response to even gentle stimuli such as breeze or a caress. This condition is called allodynia -a state in which pain is produced by innocuous stimuli.

The body's natural painkillers may yet prove to be the most promising pain relievers, pointing to one of the most important new avenues in drug development. The brain may signal the release of painkillers found in the spinal cord, including serotonin, norepinephrine, and opioid-like chemicals. Many pharmaceutical companies are working to synthesize these substances in laboratories as future medications.

Endorphins and enkephalins are other natural painkillers. Endorphins may be responsible for the "feel good" effects experienced by many people after rigorous exercise; they are also implicated in the pleasurable effects of smoking.

Similarly, peptides, compounds that make up proteins in the body, play a role in pain responses. Mice bred experimentally to lack a gene for two peptides called tachykinins-neurokinin A and substance P-have a reduced response to severe pain. When exposed to mild pain, these mice react in the same way as mice that carry the missing gene. But when exposed to more severe pain, the mice exhibit a reduced pain response. This suggests that the two peptides are involved in the production of pain sensations, especially moderate-to-severe pain. Continued research on tachykinins, conducted with support from the NINDS, may pave the way for drugs tailored to treat different severities of pain.

Scientists are working to develop potent pain-killing drugs that act on receptors for the chemical acetylcholine. For example, a type of frog native to Ecuador has been found to have a chemical in its skin called epibatidine, derived from the frog's scientific name, Epipedobates tricolor. Although highly toxic, epibatidine is a potent analgesic and, surprisingly, resembles the chemical nicotine found in cigarettes. Also under development are other less toxic compounds that act on acetylcholine receptors and may prove to be more potent than morphine but without its addictive properties.

The idea of using receptors as gateways for pain drugs is a novel idea, supported by experiments involving substance P. Investigators have been able to isolate a tiny population of neurons, located in the spinal cord, that together form a major portion of the pathway responsible for carrying persistent pain signals to the brain. When animals were given injections of a lethal cocktail containing substance P linked to the chemical saporin, this group of cells, whose sole function is to communicate pain, were killed. Receptors for substance P served as a portal or point of entry for the compound. Within days of the injections, the targeted neurons, located in the outer layer of the spinal cord along its entire length, absorbed the compound and were neutralized. The animals' behavior was completely normal; they no longer exhibited signs of pain following injury or had an exaggerated pain response. Importantly, the animals still responded to acute, that is, normal, pain. This is a critical finding as it is important to retain the body's ability to detect potentially injurious stimuli. The protective, early warning signal that pain provides is essential for normal functioning. If this work can be translated clinically, humans might be able to benefit from similar compounds introduced, for example, through lumbar (spinal) puncture.

Another promising area of research using the body's natural pain-killing abilities is the transplantation of chromaffin cells into the spinal cords of animals bred experimentally to develop arthritis. Chromaffin cells produce several of the body's pain-killing substances and are part of the adrenal medulla, which sits on top of the kidney. Within a week or so, rats receiving these transplants cease to exhibit telltale signs of pain. Scientists, working with support from the NINDS, believe the transplants help the animals recover from pain-related cellular damage. Extensive animal studies will be required to learn if this technique might be of value to humans with severe pain.

One way to control pain outside of the brain, that is, peripherally, is by inhibiting hormones called prostaglandins. Prostaglandins stimulate nerves at the site of injury and cause inflammation and fever. Certain drugs, including NSAIDs, act against such hormones by blocking the enzyme that is required for their synthesis.

Blood vessel walls stretch or dilate during a migraine attack and it is thought that serotonin plays a complicated role in this process. For example, before a migraine headache, serotonin levels fall. Drugs for migraine include the triptans: sumatriptan (Imitrix®), naratriptan (Amerge®), and zolmitriptan (Zomig®). They are called serotonin agonists because they mimic the action of endogenous (natural) serotonin and bind to specific subtypes of serotonin receptors.

Ongoing pain research, much of it supported by the NINDS, continues to reveal at an unprecedented pace fascinating insights into how genetics, the immune system, and the skin contribute to pain responses.

The explosion of knowledge about human genetics is helping scientists who work in the field of drug development. We know, for example, that the pain-killing properties of codeine rely heavily on a liver enzyme, CYP2D6, which helps convert codeine into morphine. A small number of people genetically lack the enzyme CYP2D6; when given codeine, these individuals do not get pain relief. CYP2D6 also helps break down certain other drugs. People who genetically lack CYP2D6 may not be able to cleanse their systems of these drugs and may be vulnerable to drug toxicity. CYP2D6 is currently under investigation for its role in pain.

In his research, the late John C. Liebeskind, a renowned pain expert and a professor of psychology at UCLA, found that pain can kill by delaying healing and causing cancer to spread. In his pioneering research on the immune system and pain, Dr. Liebeskind studied the effects of stress-such as surgery-on the immune system and in particular on cells called natural killer or NK cells. These cells are thought to help protect the body against tumors. In one study conducted with rats, Dr. Liebeskind found that, following experimental surgery, NK cell activity was suppressed, causing the cancer to spread more rapidly. When the animals were treated with morphine, however, they were able to avoid this reaction to stress.

The link between the nervous and immune systems is an important one. Cytokines, a type of protein found in the nervous system, are also part of the body's immune system, the body's shield for fighting off disease. Cytokines can trigger pain by promoting inflammation, even in the absence of injury or damage. Certain types of cytokines have been linked to nervous system injury. After trauma, cytokine levels rise in the brain and spinal cord and at the site in the peripheral nervous system where the injury occurred. Improvements in our understanding of the precise role of cytokines in producing pain, especially pain resulting from injury, may lead to new classes of drugs that can block the action of these substances.

The Two Faces of Pain: Acute and Chronic

What is pain? The International Association for the Study of Pain defines it as: An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.

It is useful to distinguish between two basic types of pain, acute and chronic, and they differ greatly.

• Acute pain, for the most part, results from disease, inflammation, or injury to tissues. This type of pain generally comes on suddenly, for example, after trauma or surgery, and may be accompanied by anxiety or emotional distress. The cause of acute pain can usually be diagnosed and treated, and the pain is self-limiting, that is, it is confined to a given period of time and severity. In some rare instances, it can become chronic.
• Chronic pain is widely believed to represent disease itself. It can be made much worse by environmental and psychological factors. Chronic pain persists over a longer period of time than acute pain and is resistant to most medical treatments. It can—and often does—cause severe problems for patients.

Gender and Pain

It is now widely believed that pain affects men and women differently. While the sex hormones estrogen and testosterone certainly play a role in this phenomenon, psychology and culture, too, may account at least in part for differences in how men and women receive pain signals. For example, young children may learn to respond to pain based on how they are treated when they experience pain. Some children may be cuddled and comforted, while others may be encouraged to tough it out and to dismiss their pain.

Many investigators are turning their attention to the study of gender differences and pain. Women, many experts now agree, recover more quickly from pain, seek help more quickly for their pain, and are less likely to allow pain to control their lives. They also are more likely to marshal a variety of resources-coping skills, support, and distraction-with which to deal with their pain.

Research in this area is yielding fascinating results. For example, male experimental animals injected with estrogen, a female sex hormone, appear to have a lower tolerance for pain-that is, the addition of estrogen appears to lower the pain threshold. Similarly, the presence of testosterone, a male hormone, appears to elevate tolerance for pain in female mice: the animals are simply able to withstand pain better. Female mice deprived of estrogen during experiments react to stress similarly to male animals. Estrogen, therefore, may act as a sort of pain switch, turning on the ability to recognize pain.

Investigators know that males and females both have strong natural pain-killing systems, but these systems operate differently. For example, a class of painkillers called kappa-opioids is named after one of several opioid receptors to which they bind, the kappa-opioid receptor, and they include the compounds nalbuphine (Nubain®) and butorphanol (Stadol®). Research suggests that kappa-opioids provide better pain relief in women.

Though not prescribed widely, kappa-opioids are currently used for relief of labor pain and in general work best for short-term pain. Investigators are not certain why kappa-opioids work better in women than men. Is it because a woman's estrogen makes them work, or because a man's testosterone prevents them from working? Or is there another explanation, such as differences between men and women in their perception of pain? Continued research may result in a better understanding of how pain affects women differently from men, enabling new and better pain medications to be designed with gender in mind.

Clarification on the use of certain pain-related terms

The word pain used without a modifier usually refers to physical pain, but it may also refer to pain in the broad sense, i.e. suffering. The latter includes physical pain and mental pain, or any unpleasant feeling, sensation, and emotion. It may be described as a private feeling of unpleasantness and aversion associated with harm or threat of harm in an individual. Care should be taken to make the appropriate distinction when required between the two meanings. For instance, philosophy of pain is essentially about physical pain, while a philosophical outlook on pain is rather about pain in the broad sense. Or, as another quite different instance, nausea or itch are not 'physical pains', but they are unpleasant sensory or bodily experience, and a person 'suffering' from severe or prolonged nausea or itch may be said 'in pain'.

Nociception, the unconscious activity induced by a harmful stimulus in sense receptors, peripheral nerves, spinal column and brain, should not be confused with physical pain, which is a conscious experience. Nociception or noxious stimuli usually cause pain, but not always, and sometimes pain occurs without them.

Qualifiers, such as mental, emotional, psychological, and spiritual, are often used for referring to more specific types of pain or suffering. In particular, 'mental pain' may be used in relationship with 'physical pain' for distinguishing between two wide categories of pain. A first caveat concerning such a distinction is that it uses 'physical pain' in a sense that normally includes not only the 'typical sensory experience' of 'physical pain' but also other unpleasant bodily experience such as itch or nausea. A second caveat is that the terms physical or mental should not be taken too literally: physical pain, as a matter of fact, happens through conscious minds and involves emotional aspects, while mental pain happens through physical brains and, being an emotion, it involves important bodily physiological aspects.

The term unpleasant or unpleasantness commonly means painful or painfulness in a broad sense. It is also used in (physical) pain science for referring to the affective dimension of pain, usually in contrast with the sensory dimension. For instance: “Pain-unpleasantness is often, though not always, closely linked to both the intensity and unique qualities of the painful sensation.” Pain science acknowledges, in a puzzling challenge to IASP definition, that pain may be experienced as a sensation devoid of any unpleasantness: see below pain asymbolia.

Suffering is sometimes used in the specific narrow sense of physical pain, but more often it refers to mental pain, or more often yet to pain in the broad sense. Suffering is described as an individual's basic affective experience of unpleasantness and aversion associated with harm or threat of harm.

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

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

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

The A to Z of Pain

Hundreds of pain syndromes or disorders make up the spectrum of pain. There are the most benign, fleeting sensations of pain, such as a pin prick. There is the pain of childbirth, the pain of a heart attack, and the pain that sometimes follows amputation of a limb. There is also pain accompanying cancer and the pain that follows severe trauma, such as that associated with head and spinal cord injuries. A sampling of common pain syndromes follows, listed alphabetically.

Arachnoiditis is a condition in which one of the three membranes covering the brain and spinal cord, called the arachnoid membrane, becomes inflamed. A number of causes, including infection or trauma, can result in inflammation of this membrane. Arachnoiditis can produce disabling, progressive, and even permanent pain.

Arthritis. Millions of Americans suffer from arthritic conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and gout. These disorders are characterized by joint pain in the extremities. Many other inflammatory diseases affect the body's soft tissues, including tendonitis and bursitis.

Back pain has become the high price paid by our modern lifestyle and is a startlingly common cause of disability for many Americans, including both active and inactive people. Back pain that spreads to the leg is called sciatica and is a very common condition (see below). Another common type of back pain is associated with the discs of the spine, the soft, spongy padding between the vertebrae (bones) that form the spine. Discs protect the spine by absorbing shock, but they tend to degenerate over time and may sometimes rupture. Spondylolisthesis is a back condition that occurs when one vertebra extends over another, causing pressure on nerves and therefore pain. Also, damage to nerve roots (see Spine Basics in the Appendix) is a serious condition, called radiculopathy, that can be extremely painful. Treatment for a damaged disc includes drugs such as painkillers, muscle relaxants, and steroids; exercise or rest, depending on the patient's condition; adequate support, such as a brace or better mattress and physical therapy. In some cases, surgery may be required to remove the damaged portion of the disc and return it to its previous condition, especially when it is pressing a nerve root. Surgical procedures include discectomy, laminectomy, or spinal fusion (see section on surgery in How is Pain Treated? for more information on these treatments).

Burn pain can be profound and poses an extreme challenge to the medical community. First-degree burns are the least severe; with third-degree burns, the skin is lost. Depending on the injury, pain accompanying burns can be excruciating, and even after the wound has healed patients may have chronic pain at the burn site.

Central pain syndrome-see "Trauma" below.

Cancer pain can accompany the growth of a tumor, the treatment of cancer, or chronic problems related to cancer's permanent effects on the body. Fortunately, most cancer pain can be treated to help minimize discomfort and stress to the patient.

Headaches affect millions of Americans. The three most common types of chronic headache are migraines, cluster headaches, and tension headaches. Each comes with its own telltale brand of pain.

• Migraines are characterized by throbbing pain and sometimes by other symptoms, such as nausea and visual disturbances. Migraines are more frequent in women than men. Stress can trigger a migraine headache, and migraines can also put the sufferer at risk for stroke.
• Cluster headaches are characterized by excruciating, piercing pain on one side of the head; they occur more frequently in men than women.
• Tension headaches are often described as a tight band around the head.

Head and facial pain can be agonizing, whether it results from dental problems or from disorders such as cranial neuralgia, in which one of the nerves in the face, head, or neck is inflamed. Another condition, trigeminal neuralgia (also called tic douloureux), affects the largest of the cranial nerves and is characterized by a stabbing, shooting pain.

Muscle pain can range from an aching muscle, spasm, or strain, to the severe spasticity that accompanies paralysis. Another disabling syndrome is fibromyalgia, a disorder characterized by fatigue, stiffness, joint tenderness, and widespread muscle pain. Polymyositis, dermatomyositis, and inclusion body myositis are painful disorders characterized by muscle inflammation. They may be caused by infection or autoimmune dysfunction and are sometimes associated with connective tissue disorders, such as lupus and rheumatoid arthritis.

Myofascial pain syndromes affect sensitive areas known as trigger points, located within the body's muscles. Myofascial pain syndromes are sometimes misdiagnosed and can be debilitating. Fibromyalgia is a type of myofascial pain syndrome.

Neuropathic pain is a type of pain that can result from injury to nerves, either in the peripheral or central nervous system (see The Nervous Systems in the Appendix). Neuropathic pain can occur in any part of the body and is frequently described as a hot, burning sensation, which can be devastating to the affected individual. It can result from diseases that affect nerves (such as diabetes) or from trauma, or, because chemotherapy drugs can affect nerves, it can be a consequence of cancer treatment. Among the many neuropathic pain conditions are diabetic neuropathy (which results from nerve damage secondary to vascular problems that occur with diabetes); reflex sympathetic dystrophy syndrome (see below), which can follow injury; phantom limb and post-amputation pain (see Phantom Pain in the Appendix), which can result from the surgical removal of a limb; postherpetic neuralgia, which can occur after an outbreak of shingles; and central pain syndrome, which can result from trauma to the brain or spinal cord.

Reflex sympathetic dystrophy syndrome, or RSDS, is accompanied by burning pain and hypersensitivity to temperature. Often triggered by trauma or nerve damage, RSDS causes the skin of the affected area to become characteristically shiny. In recent years, RSDS has come to be called complex regional pain syndrome (CRPS); in the past it was often called causalgia.

Repetitive stress injuries are muscular conditions that result from repeated motions performed in the course of normal work or other daily activities. They include:

• writer's cramp, which affects musicians and writers and others,
• compression or entrapment neuropathies, including carpal tunnel syndrome, caused by chronic overextension of the wrist and
• tendonitis or tenosynovitis, affecting one or more tendons.

Sciatica is a painful condition caused by pressure on the sciatic nerve, the main nerve that branches off the spinal cord and continues down into the thighs, legs, ankles, and feet. Sciatica is characterized by pain in the buttocks and can be caused by a number of factors. Exertion, obesity, and poor posture can all cause pressure on the sciatic nerve. One common cause of sciatica is a herniated disc (see Spine Basics in the Appendix).

Shingles and other painful disorders affect the skin. Pain is a common symptom of many skin disorders, even the most common rashes. One of the most vexing neurological disorders is shingles or herpes zoster, an infection that often causes agonizing pain resistant to treatment. Prompt treatment with antiviral agents is important to arrest the infection, which if prolonged can result in an associated condition known as postherpetic neuralgia. Other painful disorders affecting the skin include:

• vasculitis, or inflammation of blood vessels;
• other infections, including herpes simplex;
• skin tumors and cysts, and
• tumors associated with neurofibromatosis, a neurogenetic disorder.

Sports injuries are common. Sprains, strains, bruises, dislocations, and fractures are all well-known words in the language of sports. Pain is another. In extreme cases, sports injuries can take the form of costly and painful spinal cord and head injuries, which cause severe suffering and disability.

Spinal stenosis refers to a narrowing of the canal surrounding the spinal cord. The condition occurs naturally with aging. Spinal stenosis causes weakness in the legs and leg pain usually felt while the person is standing up and often relieved by sitting down.

Surgical pain may require regional or general anesthesia during the procedure and medications to control discomfort following the operation. Control of pain associated with surgery includes presurgical preparation and careful monitoring of the patient during and after the procedure.

Temporomandibular disorders are conditions in which the temporomandibular joint (the jaw) is damaged and/or the muscles used for chewing and talking become stressed, causing pain. The condition may be the result of a number of factors, such as an injury to the jaw or joint misalignment, and may give rise to a variety of symptoms, most commonly pain in the jaw, face, and/or neck muscles. Physicians reach a diagnosis by listening to the patient's description of the symptoms and by performing a simple examination of the facial muscles and the temporomandibular joint.

Trauma can occur after injuries in the home, at the workplace, during sports activities, or on the road. Any of these injuries can result in severe disability and pain. Some patients who have had an injury to the spinal cord experience intense pain ranging from tingling to burning and, commonly, both. Such patients are sensitive to hot and cold temperatures and touch. For these individuals, a touch can be perceived as intense burning, indicating abnormal signals relayed to and from the brain. This condition is called central pain syndrome or, if the damage is in the thalamus (the brain's center for processing bodily sensations), thalamic pain syndrome. It affects as many as 100,000 Americans with multiple sclerosis, Parkinson's disease, amputated limbs, spinal cord injuries, and stroke. Their pain is severe and is extremely difficult to treat effectively. A variety of medications, including analgesics, antidepressants, anticonvulsants, and electrical stimulation, are options available to central pain patients.

Vascular disease or injury-such as vasculitis or inflammation of blood vessels, coronary artery disease, and circulatory problems-all have the potential to cause pain. Vascular pain affects millions of Americans and occurs when communication between blood vessels and nerves is interrupted. Ruptures, spasms, constriction, or obstruction of blood vessels, as well as a condition called ischemia in which blood supply to organs, tissues, or limbs is cut off, can also result in pain.

Pain in Aging and Pediatric Populations: Special Needs and Concerns

Pain is the number one complaint of older Americans, and one in five older Americans takes a painkiller regularly. In 1998, the American Geriatrics Society (AGS) issued guidelines* for the management of pain in older people. The AGS panel addressed the incorporation of several non-drug approaches in patients' treatment plans, including exercise. AGS panel members recommend that, whenever possible, patients use alternatives to aspirin, ibuprofen, and other NSAIDs because of the drugs' side effects, including stomach irritation and gastrointestinal bleeding. For older adults, acetaminophen is the first-line treatment for mild-to-moderate pain, according to the guidelines. More serious chronic pain conditions may require opioid drugs (narcotics), including codeine or morphine, for relief of pain.

Pain in younger patients also requires special attention, particularly because young children are not always able to describe the degree of pain they are experiencing. Although treating pain in pediatric patients poses a special challenge to physicians and parents alike, pediatric patients should never be undertreated. Recently, special tools for measuring pain in children have been developed that, when combined with cues used by parents, help physicians select the most effective treatments.

Nonsteroidal agents, and especially acetaminophen, are most often prescribed for control of pain in children. In the case of severe pain or pain following surgery, acetaminophen may be combined with codeine.

Mechanism

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

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

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

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

1. Superficial somatic pain (or cutaneous pain) is caused by injury to the skin or superficial tissues. Cutaneous nociceptors terminate just below the skin, and due to the high concentration of nerve endings, produce a sharp, well-defined, localized pain of short duration. Examples of injuries that produce cutaneous pain include minor wounds, and minor (first degree) burns.
   
   
2. Deep somatic pain originates from ligaments, tendons, bones, blood vessels, fasciae, and muscles. It is detected with somatic nociceptors. The scarcity of pain receptors in these areas produces a dull, aching, poorly-localized pain of longer duration than cutaneous pain; examples include sprains, broken bones, and myofascial pain.
   
   
3. Visceral pain originates from body's viscera, or organs. Visceral nociceptors are located within body organs and internal cavities. The even greater scarcity of nociceptors in these areas produces pain that is usually more aching or cramping and of a longer duration than somatic pain. Visceral pain may be well-localized, but often it is extremely difficult to localize, and several injuries to visceral tissue exhibit "referred" pain, where the sensation is localized to an area completely unrelated to the site of injury.

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

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

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

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

Evolutionary and behavioral role

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

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

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

Chronic pain, in which the pain becomes pathological rather than beneficial, may be an exception to the idea that pain is helpful to survival, although some specialists believe that psychogenic chronic pain exists as a protective distraction to keep dangerous repressed emotions such as anger or rage unconscious. 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.

Diagnosis

There is no way to tell how much pain a person has. No test can measure the intensity of pain, no imaging device can show pain, and no instrument can locate pain precisely. Sometimes, as in the case of headaches, physicians find that the best aid to diagnosis is the patient's own description of the type, duration, and location of pain. Defining pain as sharp or dull, constant or intermittent, burning or aching may give the best clues to the cause of pain. These descriptions are part of what is called the pain history, taken by the physician during the preliminary examination of a patient with pain.

Physicians, however, do have a number of technologies they use to find the cause of pain. Primarily these include:

• Electrodiagnostic procedures include electromyography (EMG), nerve conduction studies, and evoked potential (EP) studies. Information from EMG can help physicians tell precisely which muscles or nerves are affected by weakness or pain. Thin needles are inserted in muscles and a physician can see or listen to electrical signals displayed on an EMG machine. With nerve conduction studies the doctor uses two sets of electrodes (similar to those used during an electrocardiogram) that are placed on the skin over the muscles. The first set gives the patient a mild shock that stimulates the nerve that runs to that muscle. The second set of electrodes is used to make a recording of the nerve's electrical signals, and from this information the doctor can determine if there is nerve damage. EP tests also involve two sets of electrodes-one set for stimulating a nerve (these electrodes are attached to a limb) and another set on the scalp for recording the speed of nerve signal transmission to the brain.
• Imaging, especially magnetic resonance imaging or MRI, provides physicians with pictures of the body's structures and tissues. MRI uses magnetic fields and radio waves to differentiate between healthy and diseased tissue.
• A neurological examination in which the physician tests movement, reflexes, sensation, balance, and coordination.
• X-rays produce pictures of the body's structures, such as bones and joints

To establish an understanding of an individual's pain, health-care practitioners will typically try to establish certain characteristics of the pain: site, onset and offset, character, radiation, associated symptoms, time pattern, exacerbating and ameliorating factors and severity.

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

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

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

Verbal characterization

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

Point to a number or face that shows intensity of pain.

Intensity

Pain may range in intensity from slight through severe to agonizing and can appear as constant or intermittent. The threshold of pain varies widely between individuals. Many attempts have been made to create a pain scale that can be used to quantify pain, for instance on a numeric scale that ranges from 0 to 10 points. In this scale, zero would be no pain at all and ten would be the worst pain imaginable. The purpose of these scales is to monitor an individual's pain over time, allowing care-givers to see how a patient responds to therapy for example. Accurate quantification can also allow researchers to compare results between groups of patients.

Localization

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

Nurses use the PQRST method to qualify the pain

P = provocation / palliation : what were you doing when the pain started? What caused it? What makes it better? worse? What seems to trigger it? Stress? Position? Certain activities? Arguments? Does it seem to be getting better, or getting worse, or does it remain the same? What relieves it: changing diet? changing position? taking medications? being active? resting? What makes (the problem) worse?

Q = quality / quantity : What does it feel like? Is it sharp? Dull? Stabbing? Burning? Crushing? throbbing? nauseating? shooting? twisting? stretching? Other? (The person who is suffering the pain should describe the pain, rather than saying what they think you would like to hear.) How does it feel, look or sound? How much of it is there?

R = region / radiation : Where is the pain located? Does the pain radiate (i.e. spread to another location, eg. pain source is from thumb but pain spreads to elbow)? Where does it radiate? Is it all in one place? Does it go anywhere else? Did it start elsewhere and now localised to one spot? Does it feel like it travels/moves around?

S = severity scale : How severe is the pain on a scale of 0 - 10, zero being no pain at all and 10 being the worst pain ever? Does it interfere with activities? How bad is it when it's at its worst? Does it force you to sit down, lie down, slow down? How long does an episode last?

T = timing : When did the pain start, at what time? How long did it last? How often does it occur? Is it sudden or gradual? What were you doing when you first experienced or noticed it? How often do you experience it: hourly? daily? weekly? monthly? When do you usually experience it: daytime? night? in the early morning? Are you ever awakened by it? Does it lead to anything else? Is it accompanied by other signs and symptoms? Does it ever occur before, during or after meals? Does it occur seasonally?

Other questions to ask when assessing a person in pain:

• Any medication or allergies?
• Does it hurt on deep inspiration?
• Activity at onset?
• Any history of pain?
• Is it the same?
• Different?
• Any family history of heart disease, lung problems, diabetes, stroke, hypertension?
• Check LOC
• Pupils?
• JVD?
• Midline trachea?
• Any recent trauma?

The purpose for these questions are to be as specific as possible in the description of the pain : when and where, what it feels like... The more specific and detailed information, the better it will be to diagnose the problem/cause and find a way to alleviate it.

Chest pain

Heart & Aorta

• Acute pericarditis
• Angina pectoris
• Aortic regurgitation
• Aortic stenosis
• Dissecting aneurysm
• Hypertrophic obstructive cardiomyopathy
• Mitral valve prolapse
• Myocardial infarction
• Non-dissecting aneurysm

Respiratory

• Acute pulmonary hypertension
• Acute tracheobronchitis
• Atelectasis
• Bronchiectasis
• Chronic pulmonary hypertension
• Endobronchial carcinoma
• Epidemic pleurodynia
• Intra-pulmonary carcinoma
• Lung abscess
• Lung cancer
• Mediastinal spread
• Pancoast's syndrome
• Pleural spread
• Pleuritis
• Pneumonia
• Pneumothorax
• Pulmonary embolism

Esophagus

• Esophageal cancer
• Esophageal tear
• Esophagitis

• Acute esophagitis
• Chronic esophagitis

• Gastro-esophageal reflux disease
• Hiatus hernia
• Motor disorders

Mediastinum

• Mediastinal carcinoma
• Mediastinal emphysema
• Mediastinitis

• Acute mediastinitis
• Chronic mediastinitis

Diaphragm

• Acute diaphragmitis
• Diaphragmatic flutter
• Diaphragmatic pleuritis
• Diaphragmatic spasm

Nerve pain

• Epidural compression
• Extra-medullary (outside spinal cord)
• Intercostal nerves
• Intra-medullary (inside spinal cord)
• Mechanical compression
• Neuropathies
• Paravertebral compression
• Post herpetic neuralgia
• Primary nerve tumors
• Shingles
• Tabes dorsalis
• Thoracic nerve rootlets
• Thoracic spinal cord
• Thoracic spinal nerves
• Vertebral compression

Musculoskeletal

• Ankylosing spondylitis
• Costal cartilages
• Costchondral fracture
• Costchondral dislocation
• Costochondritis
• Costovertebral joint arthritis
• Diffuse idiopathic skeletal hyperostosis
• Facet joint syndrome
• Inflammatory disease
• Muscle pain
• Primary & secondary tumors
• Rheumatoid arthritis
• Osteoarthritis
• Rib fractures
• Rib tumors
• Slipping rib syndrome
• Sternal fracture
• Sternoclavicular arthritis
• Sternum
• Thoracic arthritis
• Thoracic deformity
• Thoracic spine
• Tietze's syndrome
• Vertebral fracture
• Xiphoidalgia

Chest wall

• Acute disorders

• Acute mastalgia
• Acute skin disorders
• Burns & trauma
• Deep axillary abscesses
• Post-operative pain

• Chronic disorders

• Adiposis dolorosa
• Breast cancer
• Chest wall phlebitis
• Chronic mastalgia
• Post-mastectomy syndrome
• Post-thoracotomy syndrome
• Scleroderma

Referred pain

• Abdominal organs

• Acute cholecystitis
• Acute pancreatitis
• Biliary colic
• Gas entrapment
• Pancoast's syndrome
• Peptic ulcer disease
• Perforated ulcer
• Subphrenic abscess

• Cervical spine

• Cervical disc protrusion
• Cervical nerve entrapment
• Thoracic outlet syndrome

Psychological

• Acute anxiety
• Chronic anxiety
• Depression
• Hypochondriasis
• Operant pain

Abdominal pain

Gastrointestinal tract

• Actinomycosis
• Acute appendicitis
• Afferent loop syndrome
• Amoebic dysentry
• Colon cancer
• Crohn's disease
• Diverticulitis
• Dumping syndrome
• Duodenal ulcer
• Gastric cancer
• Gastric granuloma
• Gastric ulcer
• Gastritis

• Acute erosive gastritis
• Chronic erosive gastritis

• Hiatus hernia
• Hypertrophic gastropathy
• Infectious enterocolitis
• Intestinal ischemia
• Irritable bowel syndrome
• Large bowel obstruction
• Neurogenic obstruction
• Nonulcer dyspepsia
• Penetrating ulcer
• Peptic ulcer
• Perforated ulcer
• Phlegmonous gastritis
• Post-gastrectomy pain syndromes
• Postradiation enterocolitis
• Pyloric stenosis
• Pylorospasm
• Reflux alkaline syndrome
• Regional ileitis
• Small bowel obstruction
• Too small gastric pouch
• Tuberculosis
• Typhoid
• Ulcerative colitis
• Volvulus

Gallbladder

• Acute cholecystitis
• Biliary colic
• Gallbladder carcinoma
• Gallbladder empyema
• Postcholecystectomy syndrome

Liver

• Acute hepatitis
• Gonococcal perihepatitis
• Liver abscess
• Liver carcinoma
• Metastatic liver tumors
• Primary liver tumors

Pancreas

• Acute pancreatitis
• Chronic pancreatitis
• Pancreatic carcinoma
• Pancreatic duct occlusion

Spleen

• Perisplenitis
• Splenic abscess
• Splenic infarction
• Splenic rupture
• Splenomegaly

Kidney & Ureters

• Congenital

• Calyceal diverticulum
• Horseshoe kidney
• Polycystic kidney disease
• Simple single cyst
• Vesicoureteral reflux

• Acquired

• Acute intermittent hydronephrosis
• Acute pyelonephritis
• Blood clot obstruction
• Hypertensive renal vascular disease
• Idiopathic nephralgia
• Infundibular cancer
• Infundibular stenosis
• Metastatic renal cell carcinoma
• Non-stone obstruction
• Ovarian vein syndrome
• Perinephritic abscess
• Pyelonephrosis
• Renal stones / ureteric stones
• Renal abscess
• Renal artery aneurysm
• Renal artery occlusion
• Renal carbuncle
• Renal cell carcinoma
• Renal echinococcus
• Renal infection
• Renal pelvis carcinoma
• Renal sarcoma
• Renal vein thrombosis
• Retroperitoneal fibrosis
• Sloughed renal papilla
• Tuberculosis

Intra-abdominal vascular disorders

• Acute mesenteric artery occlusion
• Chronic mesenteric insufficiency
• Intra-abdominal aortic aneurysm
• Vasculitis

Peritoneal Disorders

• Acute peritonitis
• Carcinomatosis
• Familial paroxysmal peritonitis
• Granulomatous peritonitis
• Mesothelioma
• Peritoneal cancer

Mesenteric Disorders

• Mesenteric inflammatory disease
• Mesenteric tumors
• Torsion of the omentum

Diaphragmatic Disorders

• Diaphragmatic cysts
• Diaphragmatic herniation
• Diaphragmatic rupture
• Diaphragmatic tumors

Other intra-abdominal disorders

• Abdominal migraine
• Anterior retroperitoneal abscess
• Gas entrapment syndromes
• Hepatic abscess
• Intra-abdominal abscess
• Mid-abdominal abscess
• Neurogenic intestinal obstruction
• Pancreatic abscess
• Subhepatic abscess
• Subphrenic abscess

Systemic disorders

• Acute hemorrhoid crises
• Acute intermittent porphyria
• Biological factors
• Chronic hemolytic anemia
• Endocrine disturbances
• Food allergy
• Hematological disorders
• Metabolic disorders
• Sickle cell anemia
• Spider bite
• Systemic toxic disorders

Extra-abdominal disorders

• Neuropathic pain

• Abdominal cutaneous nerve entrapment
• Brain / brainstem
• Intercostal neuralgia
• Lower thoracic spinal cord
• Spinal nerve roots T₅ - L₁

• Musculoskeletal

• 12^th rib syndrome
• Myofascial pain
• Slipping rib syndrome
• Traumatic muscle hematoma
• Xiphoidalgia

• Abdominal wall

• Painful scars

• Dermatological disorders

• Post burn scars
• Post-operative pain

Psychogenic pain

• Delusional pain / hallucinatory pain
• Depression
• Hysterical / hypochondriacal pain
• Learned pain
• Somatoform pain

Pelvic pain

Gynaecological

• Normal pregnancy
• Acute pain

• Acute pelvic inflammatory disease
• Acute endometritis
• Acute infections

• Recurrent pain

• Primary dysmenorrhoea
• Secondary dysmenorrhoea

• Chronic pain

• Chronic PID
• Chronic endometriosis

• Uterine disorders

• Enlarged uterus
• Fibroid degeneration
• Round ligament stretching
• Developmental abnormalities
• Uterine prolapse
• Vascular disorders

• Pelvic muscle spasm
• Gynaecological cancers

• Cervical cancer
• Endometrial cancer
• Ovarian cancer

• Mittelschmerz
• Pregnancy complications

• Premature labour
• Ruptured ectopic pregnancy
• Miscarriage

• Vulva disease / vagina disorders

• Acute infections

• Canchroid infection
• Chlamydia infection
• Herpetic infection
• Perineal abscess
• Vulval infections

• Acute trauma
• Allergic reactions
• Chronic infections

• Bacteria
• Fungus
• Parasites
• Pinworms
• Ringworm
• Sweat gland infection

• Ovarian disorders

• Functional ovarian cyst
• Ovarian cyst bleed
• Ovarian tumor torsion
• Ruptured ovarian follicle
• Twisted ovarian cyst

Urological

• Bladder

• Acute cystitis
• Bladder cancer
• Chronic cystitis
• Chronic TB cystitis
• Interstitial cystitis
• Post-radiation cystitis
• Schistosomal cystitis

• Urethra

• Acute urethritis
• Trauma

• Male

• Acute urethritis
• Urethral syndrome

• Prostate

• Acute prostatitis
• Chronic prostatitis
• Prostatic stones
• Prostate cancer
• Seminal vesicles

• Acute epididymitis
• Testicles

• Orchiodynia
• Orchitis
• Seminoma
• Teratoma
• Testicular appendix torsion
• Testicular cancer
• Testicular torsion

• Penis

• Balanitis
• Herpes infection
• Paraphimosis
• Penile cancer
• Peyronie's disease
• Priapism

Musculoskeletal

• Coccydynia
• Gluteal muscle syndrome
• Levator muscle spasm
• Lower abdominal muscle syndrome
• Myofascial syndromes
• Osteomyelitis
• Paget's disease
• Pelvic bone cancer
• Pelvic bone disorders
• Pelvic fractures
• Pelvic muscle disorders
• Pelvic sprains
• Pelvic trauma
• Post-episiotomy
• Post-laminectomy
• Post-traumatic
• Primary tumors
• Rectus abdominis syndrome
• Secondary tumors
• Septic arthritis

Neurological

• Central pain syndromes
• Lesions inside spinal cord conus
• Lesions outside spinal cord conus
• Spinal cord compression
• Caudal equina arachnoiditis
• Spinal nerves
• Herpes zoster (shingles)
• Peripheral neuropathy
• Groin neuralgia
• Obstetric palsy
• Pudendal neuropathy
• Pudendal neuralgia
• Phantom pelvic pain
• Phantom bladder pain
• Phantom anus pain

Dermatological

• Perianal / rectal area

• Local rectal lesions
• Haemorrhoids
• Proctitis
• Anal fissures
• Rectal ulcers
• Anorectal abscesses
• Rectal bacterial infection
• Rectal cancers
• Rectal boils
• Anal itch

• Perineum / genitals

• Superficial trauma
• Venereal ulcers / granulomas
• Infected sweat glands

Referred pain

• Referred pelvic pain
• Referred perineal pain
• Lower colon
• Prostate / seminal vesicles
• Bladder
• Uterus / ovaries

Psychological

• Gynaecological
• Pelvic
• Perineal
• Rectal
• Testicles

Low back, hip and leg pain

Lower Back pain + no radiation to the leg

• Abdominal conditions
• Arthritides
• Destructive bone lesions
• Developmental disorders
• Diseases of the kidney
• Diseases of the pelvic organs
• Fracture dislocation without nerve compression
• Idiopathic scoliosis
• Increased muscle tension or spasm
• Infective arthritis
• Low back pain and psychiatric illness
• Low back pain caused by operant mechanisms
• Lumbosacral strain
• Metabolic
• Muscle strain
• Myofascial pain with trigger points (TPs)
• Osteoarthritis (degenerative)
• Pain of psychological origin
• Post traumatic spondylosis
• Postoperative reflex spasm
• Postural disorders
• Prostate gland
• Psychophysiological
• Rectosigmoid colon
• Referred pain
• Referred somatic pain
• Renal stones
• Arterial obstruction
• Retrocaecal appendicitis
• Retroperitoneal masses
• Rheumatoid arthritis of the lumbar spine
• Rheumatoid arthritis of the sacroiliac joint
• Spinal neoplasms
• Trauma
• Uterus & ovaries
• Vertebral epiphysitis (Scheuermann's disease)
• Vertebral infections

Low Back Pain + radiation to the leg + no neurological deficit

• Acute + chronic degenerative conditions
• Ankylosing spondylitis
• Aortoiliac obstruction
• Chronic muscle contracture
• Contracture of fascia lata + iliotibial band
• Epidural abscess
• Facet syndrome
• Fibromyalgia
• Myofascial pain syndrome with TPs
• Primary & secondary sacroiliac joint disorders
• Spinal joints
• Spinal ligaments
• Spinal stenosis
• Spondylolisthesis

Back Pain + radiation to the leg + neurological deficit

• Lesions inside the spine but outside the spinal cord
• Spinal cord diseases

• Intrinsic spinal cord lesions
• Spinal nerve root radiculopathy
• Lumbosacral plexus lesions
• Cauda equina lesions

• Lumbar disc protrusion
• Vertebral dislocation
• Vertebral fracture
• Other causes

Hip pain

• Traumatic lesions

• Fractures in the elderly
• Fractures in the young
• Hip dislocation

• Acute arthritis

• Tuberculosis
• Infant hip infections
• Hemarthrosis
• Transient synovitis

• Chronic arthritis

• Rheumatoid arthritis
• Gout
• Psoriasis
• Degenerative osteoarthritis

• Pigmented villonodular synovitis
• Apophyseal (growth plate) disorders
• Perthes disease
• Slipped capital femoral epiphysis
• Extra-articular disorders

• Trochanteric bursitis
• Iliopectineal bursitis
• Ischiogluteal bursitis

• Cancer (primary or secondary)
• Metabolic disorders / endocrine disorders

• Paget's disease of bone
• Osteonecrosis

Thigh pain

• Contusion of quadriceps or other muscles
• Femoral neuralgia
• Femur infections
• Femur tumors
• Meralgia paraesthetica
• Musculoskeletal disorders
• Myofascial disorders
• Myofascial syndrome with TPs
• Nervous system disorders
• Obturator neuralgia
• Postoperative quadriceps muscle spasm
• Quadriceps rupture
• Referred pain
• Sciatic neuralgia
• Traumatic femur lesions
• Other femur diseases
• Other muscle disorders

Knee pain

• Arthralgia
• Arthritis
• Arthrosis
• Bursitis
• Cartilage injuries
• Chondromalacia patellae
• Chronic knee pain
• Degenerative osteoarthritis
• Infection / inflammation
• Infrapatellar fat pad
• Ligament / capsular injuries
• Loose bodies
• Myofascial pain syndrome
• Osteochondritis dissecans
• Other joint disorders
• Other painful knee joint disorders
• Posterior knee swellings / cysts
• Quadriceps rupture
• Quadriceps tendon rupture
• Spontaneous osteonecrosis
• Synovitis
• Thigh muscles
• Trauma, Fracture / dislocation
• Tumors

Lower Leg pain

• Abscess
• Bone disorders
• Bone infections
• Bone tumors
• Compartment syndrome
• Gastrocnemius rupture
• Generalized muscle pain
• Intermittent claudication
• Myofascial pain syndrome with TPs
• Muscle tendon rupture
• Muscle spasm
• Nerve entrapment syndromes
• Peripheral vascular disease
• Peroneal neuralgia
• Saphenous neuralgia
• Tenosynovitis
• Tibial neuralgia
• Trauma

• Dislocation of fibula
• Dislocation of tibia
• Fracture of fibula
• Fracture of tibia

• Other muscle disorders

Ankle & foot pain

• Ankle dislocation
• Ankle fracture
• Ankle laxity
• Ankle sprain
• Arthritis
• Bursitis
• Calcaneal paratendintis
• Claw toe
• Degenerative osteoarthritis
• Disorders of the whole foot
• Foot deformities
• Forefoot pain
• Ganglion
• Gout
• Great toe disorders
• Hallux rigidus
• Hallux valgus
• Hammer toe
• Heel pain
• Hindfoot pain
• Inflammation
• Ingrown toenail
• Lisfranc's joint instability
• Medial arch strain
• Metatarsal head osteochondritis
• Metatarsalgia
• Midfoot pain
• Morton's neuroma
• Navicular osteochondritis
• Osteochondritis dissecans
• Painful heel pad
• Peroneal tendon dislocation
• Pes cavus (hollow foot)
• Pes planus (flat foot)
• Plantar fasciitis
• Posterior tibial tendon insufficiency
• Rheumatoid arthritis
• Sesamoiditis
• Small toe disorders
• Stress fracture
• Subtalar arthritis
• Tarsal coalition
• Tarsal tunnel syndrome
• Trauma

Other lower limb disorders

• Acrocyanosis
• Acute arterial occlusion
• Acute deep vein thrombosis
• Acute thrombophlebitis
• Arteriosclerosis obliterans
• Causalgia (CRPS 2)
• Chronic arterial insufficiency
• Cold injuries
• Collagen disease (scleroderma)
• Diseases of veins
• Livedo reticularis
• Neuropathic pain
• Painful legs & moving toes
• Peripheral vascular disease
• Post phlebitic syndrome
• Postamputation pain
• Raynaud's disease
• Raynaud's phenomenon
• Reflex sympathetic dystrophy (CRPS 1)
• Scars
• Skin disorders
• Small arterial disease
• Thromboangiitis obliterans
• Trauma
• Ulcers
• Vasodilating disease
• Vasospastic disease

Management

Main article: Pain management

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

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

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

Anesthesia

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

Analgesia

Main article: Analgesic

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

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

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

Complementary and alternative medicine

A survey of American adults found pain was the most common reason that people use complementary and alternative medicine.

Traditional Chinese medicine views pain as a 'blocked' qi, akin to electrical resistance, with treatments such as acupuncture claimed as more effective for nontraumatic pain than traumatic pain. Although the mechanism is not fully understood, acupuncture may stimulate the release of large quantities of endogenous opioids.

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

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

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

Chili Peppers, Capsaicin, and Pain

The hot feeling, red face, and watery eyes you experience when you bite into a red chili pepper may make you reach for a cold drink, but that reaction has also given scientists important information about pain. The chemical found in chili peppers that causes those feelings is capsaicin (pronounced cap-SAY-sin), and it works its unique magic by grabbing onto receptors scattered along the surface of sensitive nerve cells in the mouth.

In 1997, scientists at the University of California at San Francisco discovered a gene for a capsaicin receptor, called the vanilloid receptor. Once in contact with capsaicin, vanilloid receptors open and pain signals are sent from the peripheral nociceptor and through central nervous system circuits to the brain. Investigators have also learned that this receptor plays a role in the burning type of pain commonly associated with heat, such as the kind you experience when you touch your finger to a hot stove. The vanilloid receptor functions as a sort of "ouch gateway," enabling us to detect burning hot pain, whether it originates from a 3-alarm habanera chili or from a stove burner.

Capsaicin is currently available as a prescription or over-the-counter cream for the treatment of a number of pain conditions, such as shingles. It works by reducing the amount of substance P found in nerve endings and interferes with the transmission of pain signals to the brain. Individuals can become desensitized to the compound, however, perhaps because of long-term damage to nerve tissue. Some individuals find the burning sensation they experience when using capsaicin cream to be intolerable, especially when they are already suffering from a painful condition, such as postherpetic neuralgia. Soon, however, better treatments that relieve pain by blocking vanilloid receptors may arrive in drugstores.

Marijuana

As a painkiller, marijuana or, by its Latin name, cannabis, continues to remain highly controversial. In the eyes of many individuals campaigning on its behalf, marijuana rightfully belongs with other pain remedies. In fact, for many years, it was sold under highly controlled conditions in cigarette form by the Federal government for just that purpose.

In 1997, the National Institutes of Health held a workshop to discuss research on the possible therapeutic uses for smoked marijuana. Panel members from a number of fields reviewed published research and heard presentations from pain experts. The panel members concluded that, because there are too few scientific studies to prove marijuana's therapeutic utility for certain conditions, additional research is needed. There is evidence, however, that receptors to which marijuana binds are found in many brain regions that process information that can produce pain.

Nerve Blocks

Nerve blocks may involve local anesthesia, regional anesthesia or analgesia, or surgery; dentists routinely use them for traditional dental procedures. Nerve blocks can also be used to prevent or even diagnose pain.

In the case of a local nerve block, any one of a number of local anesthetics may be used; the names of these compounds, such as lidocaine or novocaine, usually have an aine ending. Regional blocks affect a larger area of the body. Nerve blocks may also take the form of what is commonly called an epidural, in which a drug is administered into the space between the spine's protective covering (the dura) and the spinal column. This procedure is most well known for its use during childbirth. Morphine and methadone are opioid narcotics (such drugs end in ine or one) that are sometimes used for regional analgesia and are administered as an injection.

Neurolytic blocks employ injection of chemical agents such as alcohol, phenol, or glycerol to block pain messages and are most often used to treat cancer pain or to block pain in the cranial nerves. In some cases, a drug called guanethidine is administered intravenously in order to accomplish the block.

Surgical blocks are performed on cranial, peripheral, or sympathetic nerves. They are most often done to relieve the pain of cancer and extreme facial pain, such as that experienced with trigeminal neuralgia. There are several different types of surgical nerve blocks and they are not without problems and complications. Nerve blocks can cause muscle paralysis and, in many cases, result in at least partial numbness. For that reason, the procedure should be reserved for a select group of patients and should only be performed by skilled surgeons. Types of surgical nerve blocks include:

• Neurectomy (including peripheral neurectomy) in which a damaged peripheral nerve is destroyed.
• Spinal dorsal rhizotomy in which the surgeon cuts the root or rootlets of one or more of the nerves radiating from the spine. Other rhizotomy procedures include cranial rhizotomy and trigeminal rhizotomy, performed as a treatment for extreme facial pain or for the pain of cancer.
• Sympathectomy, also called sympathetic blockade, in which a drug or an agent such as guanethidine is used to eliminate pain in a specific area (a limb, for example). The procedure is also done for cardiac pain, vascular disease pain, the pain of reflex sympathetic dystrophy syndrome, and other conditions. The term takes its name from the sympathetic nervous system and may involve, for example, cutting a nerve that controls contraction of one or more arteries.

Special cases

Phantom pain

Main article: Phantom pain

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

Sometimes, when a limb is removed during an amputation, an individual will continue to have an internal sense of the lost limb. This phenomenon is known as phantom limb and accounts describing it date back to the 1800s. Similarly, many amputees are frequently aware of severe pain in the absent limb. Their pain is real and is often accompanied by other health problems, such as depression.

What causes this phenomenon? Scientists believe that following amputation, nerve cells "rewire" themselves and continue to receive messages, resulting in a remapping of the brain's circuitry. The brain's ability to restructure itself, to change and adapt following injury, is called plasticity (see section on Plasticity).

Our understanding of phantom pain has improved tremendously in recent years. Investigators previously believed that brain cells affected by amputation simply died off. They attributed sensations of pain at the site of the amputation to irritation of nerves located near the limb stump. Now, using imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI), scientists can actually visualize increased activity in the brain's cortex when an individual feels phantom pain. When study participants move the stump of an amputated limb, neurons in the brain remain dynamic and excitable. Surprisingly, the brain's cells can be stimulated by other body parts, often those located closest to the missing limb.

Treatments for phantom pain may include analgesics, anticonvulsants, and other types of drugs; nerve blocks; electrical stimulation; psychological counseling, biofeedback, hypnosis, and acupuncture; and, in rare instances, surgery.

Pain asymbolia

Pain science acknowledges, in a puzzling challenge to IASP definition, that pain may be experienced as a sensation devoid of any unpleasantness: this happens in a syndrome called pain asymbolia or pain dissociation, caused by conditions like lobotomy, cingulotomy or morphine analgesia. Typically, such patients report that they have pain but are not bothered by it, they recognize the sensation of pain but are mostly or completely immune to suffering from it.

Insensitivity to pain

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

Psychogenic pain

Psychogenic pain, also called psychalgia or somatoform pain, is physical pain that is caused, increased, or prolonged by mental, emotional, or behavioral factors. Headache, back pain, or stomach pain are some of the most common types of psychogenic pain. Sufferers are often stigmatized, because both medical professionals and the general public tend to think that pain from a psychological source is not "real". However, specialists consider that it is no less actual or hurtful than pain from other sources.

What is the Future of Pain Research?

In the forefront of pain research are scientists supported by the National Institutes of Health (NIH), including the NINDS. Other institutes at NIH that support pain research include the National Institute of Dental and Craniofacial Research, the National Cancer Institute, the National Institute of Nursing Research, the National Institute on Drug Abuse, and the National Institute of Mental Health. Developing better pain treatments is the primary goal of all pain research being conducted by these institutes.

Some pain medications dull the patient's perception of pain. Morphine is one such drug. It works through the body's natural pain-killing machinery, preventing pain messages from reaching the brain. Scientists are working toward the development of a morphine-like drug that will have the pain-deadening qualities of morphine but without the drug's negative side effects, such as sedation and the potential for addiction. Patients receiving morphine also face the problem of morphine tolerance, meaning that over time they require higher doses of the drug to achieve the same pain relief. Studies have identified factors that contribute to the development of tolerance; continued progress in this line of research should eventually allow patients to take lower doses of morphine.

One objective of investigators working to develop the future generation of pain medications is to take full advantage of the body's pain "switching center" by formulating compounds that will prevent pain signals from being amplified or stop them altogether. Blocking or interrupting pain signals, especially when there is no injury or trauma to tissue, is an important goal in the development of pain medications. An increased understanding of the basic mechanisms of pain will have profound implications for the development of future medicines. The following areas of research are bringing us closer to an ideal pain drug.

Systems and Imaging:

The idea of mapping cognitive functions to precise areas of the brain dates back to phrenology, the now archaic practice of studying bumps on the head. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and other imaging technologies offer a vivid picture of what is happening in the brain as it processes pain. Using imaging, investigators can now see that pain activates at least three or four key areas of the brain's cortex-the layer of tissue that covers the brain. Interestingly, when patients undergo hypnosis so that the unpleasantness of a painful stimulus is not experienced, activity in some, but not all, brain areas is reduced. This emphasizes that the experience of pain involves a strong emotional component as well as the sensory experience, namely the intensity of the stimulus.

Channels:

The frontier in the search for new drug targets is represented by channels. Channels are gate-like passages found along the membranes of cells that allow electrically charged chemical particles called ions to pass into the cells. Ion channels are important for transmitting signals through the nerve's membrane. The possibility now exists for developing new classes of drugs, including pain cocktails that would act at the site of channel activity.

Trophic Factors:

A class of "rescuer" or "restorer" drugs may emerge from our growing knowledge of trophic factors, natural chemical substances found in the human body that affect the survival and function of cells. Trophic factors also promote cell death, but little is known about how something beneficial can become harmful. Investigators have observed that an over-accumulation of certain trophic factors in the nerve cells of animals results in heightened pain sensitivity, and that some receptors found on cells respond to trophic factors and interact with each other. These receptors may provide targets for new pain therapies.

Molecular Genetics:

Certain genetic mutations can change pain sensitivity and behavioral responses to pain. People born genetically insensate to pain-that is, individuals who cannot feel pain-have a mutation in part of a gene that plays a role in cell survival. Using "knockout" animal models-animals genetically engineered to lack a certain gene-scientists are able to visualize how mutations in genes cause animals to become anxious, make noise, rear, freeze, or become hypervigilant. These genetic mutations cause a disruption or alteration in the processing of pain information as it leaves the spinal cord and travels to the brain. Knockout animals can be used to complement efforts aimed at developing new drugs.

Plasticity:

Following injury, the nervous system undergoes a tremendous reorganization. This phenomenon is known as plasticity. For example, the spinal cord is "rewired" following trauma as nerve cell axons make new contacts, a phenomenon known as "sprouting." This in turn disrupts the cells' supply of trophic factors. Scientists can now identify and study the changes that occur during the processing of pain. For example, using a technique called polymerase chain reaction, abbreviated PCR, scientists can study the genes that are induced by injury and persistent pain. There is evidence that the proteins that are ultimately synthesized by these genes may be targets for new therapies. The dramatic changes that occur with injury and persistent pain underscore that chronic pain should be considered a disease of the nervous system, not just prolonged acute pain or a symptom of an injury. Thus, scientists hope that therapies directed at preventing the long-term changes that occur in the nervous system will prevent the development of chronic pain conditions.

Neurotransmitters:

Just as mutations in genes may affect behavior, they may also affect a number of neurotransmitters involved in the control of pain. Using sophisticated imaging technologies, investigators can now visualize what is happening chemically in the spinal cord. From this work, new therapies may emerge, therapies that can help reduce or obliterate severe or chronic pain.

Hope for the Future

Thousands of years ago, ancient peoples attributed pain to spirits and treated it with mysticism and incantations. Over the centuries, science has provided us with a remarkable ability to understand and control pain with medications, surgery, and other treatments. Today, scientists understand a great deal about the causes and mechanisms of pain, and research has produced dramatic improvements in the diagnosis and treatment of a number of painful disorders. For people who fight every day against the limitations imposed by pain, the work of NINDS-supported scientists holds the promise of an even greater understanding of pain in the coming years. Their research offers a powerful weapon in the battle to prolong and improve the lives of people with pain: hope.

See Also

• Chronic pain
• Gate control theory of pain
• Coccydynia
• Neuralgia
• Neuropathy
• Transcutaneous Electrical Nerve Stimulator
• Temporomandibular joint disorder

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