Pain Management


Distinguish between two basic types of pain.

Identify the most common types of pain.

Identify available treatments for pain management.


In 1931, the French medical missionary Dr. Albert Schweitzer wrote, "Pain is a more terrible lord of mankind than even death itself." Today, pain has become the universal disorder, a serious and costly public health issue, and a challenge for family, friends, and health care providers who must give support to the individual suffering from the physical as well as the emotional consequences of pain.

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.

Two Facets 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.

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 (see The Nervous Systems in the Appendix) 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.

How is Pain Diagnosed?

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.

How is Pain Treated?

The goal of pain management is to improve function, enabling individuals to work, attend school, or participate in other day-to-day activities. Patients and their physicians have a number of options for the treatment of pain; some are more effective than others. Sometimes, relaxation and the use of imagery as a distraction provide relief. These methods can be powerful and effective, according to those who advocate their use. Whatever the treatment regime, it is important to remember that pain is treatable. The following treatments are among the most common.

Acetaminophen is the basic ingredient found in Tylenol® and its many generic equivalents. It is sold over the counter, in a prescription-strength preparation, and in combination with codeine (also by prescription).

Acupuncture dates back 2,500 years and involves the application of needles to precise points on the body. It is part of a general category of healing called traditional Chinese or Oriental medicine. Acupuncture remains controversial but is quite popular and may one day prove to be useful for a variety of conditions as it continues to be explored by practitioners, patients, and investigators.

Analgesic refers to the class of drugs that includes most painkillers, such as aspirin, acetaminophen, and ibuprofen. The word analgesic is derived from ancient Greek and means to reduce or stop pain. Nonprescription or over-the-counter pain relievers are generally used for mild to moderate pain. Prescription pain relievers, sold through a pharmacy under the direction of a physician, are used for more moderate to severe pain.

Anticonvulsants are used for the treatment of seizure disorders but are also sometimes prescribed for the treatment of pain. Carbamazepine in particular is used to treat a number of painful conditions, including trigeminal neuralgia. Another antiepileptic drug, gabapentin, is being studied for its pain-relieving properties, especially as a treatment for neuropathic pain.

Antidepressants are sometimes used for the treatment of pain and, along with neuroleptics and lithium, belong to a category of drugs called psychotropic drugs. In addition, anti-anxiety drugs called benzodiazepines also act as muscle relaxants and are sometimes used as pain relievers. Physicians usually try to treat the condition with analgesics before prescribing these drugs.

Antimigraine drugs include the triptans- sumatriptan (Imitrex®), naratriptan (Amerge®), and zolmitriptan (Zomig®)-and are used specifically for migraine headaches. They can have serious side effects in some people and therefore, as with all prescription medicines, should be used only under a doctor's care.

Aspirin may be the most widely used pain-relief agent and has been sold over the counter since 1905 as a treatment for fever, headache, and muscle soreness.

Biofeedback is used for the treatment of many common pain problems, most notably headache and back pain. Using a special electronic machine, the patient is trained to become aware of, to follow, and to gain control over certain bodily functions, including muscle tension, heart rate, and skin temperature. The individual can then learn to effect a change in his or her responses to pain, for example, by using relaxation techniques. Biofeedback is often used in combination with other treatment methods, generally without side effects. Similarly, the use of relaxation techniques in the treatment of pain can increase the patient's feeling of well-being.

Capsaicin is a chemical found in chili peppers that is also a primary ingredient in pain-relieving creams.

Chemonucleolysis is a treatment in which an enzyme, chymopapain, is injected directly into a herniated lumbar disc (see Spine Basics in the Appendix) in an effort to dissolve material around the disc, thus reducing pressure and pain. The procedure's use is extremely limited, in part because some patients may have a life-threatening allergic reaction to chymopapain.

Chiropractic refers to hand manipulation of the spine, usually for relief of back pain, and is a treatment option that continues to grow in popularity among many people who simply seek relief from back disorders. It has never been without controversy, however. Chiropractic's usefulness as a treatment for back pain is, for the most part, restricted to a select group of individuals with uncomplicated acute low back pain who may derive relief from the massage component of the therapy.

Cognitive-behavioral therapy involves a wide variety of coping skills and relaxation methods to help prepare for and cope with pain. It is used for postoperative pain, cancer pain, and the pain of childbirth.

Counseling can give a patient suffering from pain much needed support, whether it is derived from family, group, or individual counseling. Support groups can provide an important adjunct to drug or surgical treatment. Psychological treatment can also help patients learn about the physiological changes produced by pain.

COX-2 inhibitors may be effective for individuals with arthritis. For many years scientists have wanted to develop a drug that works as well as morphine but without its negative side effects. Nonsteroidal anti-inflammatory drugs (NSAIDs) work by blocking two enzymes, cyclooxygenase-1 and cyclooxygenase-2, both of which promote production of hormones called prostaglandins, which in turn cause inflammation, fever, and pain. The newer COX-2 inhibitors primarily block cyclooxygenase-2 and are less likely to have the gastrointestinal side effects sometimes produced by NSAIDs.

In 1999, the Food and Drug Administration approved a COX-2 inhibitor-celecoxib-for use in cases of chronic pain. The long-term effects of all COX-2 inhibitors are still being evaluated, especially in light of new information suggesting that these drugs may increase the risk of heart attack and stroke. Patients taking any of the COX-2 inhibitors should review their drug treatment with their doctors.

Electrical stimulation, including transcutaneous electrical stimulation (TENS), implanted electric nerve stimulation, and deep brain or spinal cord stimulation, is the modern-day extension of age-old practices in which the nerves of muscles are subjected to a variety of stimuli, including heat or massage. Electrical stimulation, no matter what form, involves a major surgical procedure and is not for everyone, nor is it 100 percent effective. The following techniques each require specialized equipment and personnel trained in the specific procedure being used:

  • TENS uses tiny electrical pulses, delivered through the skin to nerve fibers, to cause changes in muscles, such as numbness or contractions. This in turn produces temporary pain relief. There is also evidence that TENS can activate subsets of peripheral nerve fibers that can block pain transmission at the spinal cord level, in much the same way that shaking your hand can reduce pain.
  • Peripheral nerve stimulation uses electrodes placed surgically on a carefully selected area of the body. The patient is then able to deliver an electrical current as needed to the affected area, using an antenna and transmitter.
  • Spinal cord stimulation uses electrodes surgically inserted within the epidural space of the spinal cord. The patient is able to deliver a pulse of electricity to the spinal cord using a small box-like receiver and an antenna taped to the skin.
  • Deep brain or intracerebral stimulation is considered an extreme treatment and involves surgical stimulation of the brain, usually the thalamus. It is used for a limited number of conditions, including severe pain, central pain syndrome, cancer pain, phantom limb pain, and other neuropathic pains.

Exercise has come to be a prescribed part of some doctors' treatment regimes for patients with pain. Because there is a known link between many types of chronic pain and tense, weak muscles, exercise-even light to moderate exercise such as walking or swimming-can contribute to an overall sense of well-being by improving blood and oxygen flow to muscles. Just as we know that stress contributes to pain, we also know that exercise, sleep, and relaxation can all help reduce stress, thereby helping to alleviate pain. Exercise has been proven to help many people with low back pain. It is important, however, that patients carefully follow the routine laid out by their physicians.

Hypnosis, first approved for medical use by the American Medical Association in 1958, continues to grow in popularity, especially as an adjunct to pain medication. In general, hypnosis is used to control physical function or response, that is, the amount of pain an individual can withstand. How hypnosis works is not fully understood. Some believe that hypnosis delivers the patient into a trance-like state, while others feel that the individual is simply better able to concentrate and relax or is more responsive to suggestion. Hypnosis may result in relief of pain by acting on chemicals in the nervous system, slowing impulses. Whether and how hypnosis works involves greater insight-and research-into the mechanisms underlying human consciousness.

Ibuprofen is a member of the aspirin family of analgesics, the so-called nonsteroidal anti-inflammatory drugs (see below). It is sold over the counter and also comes in prescription-strength preparations.

Low-power lasers have been used occasionally by some physical therapists as a treatment for pain, but like many other treatments, this method is not without controversy.

Magnets are increasingly popular with athletes who swear by their effectiveness for the control of sports-related pain and other painful conditions. Usually worn as a collar or wristwatch, the use of magnets as a treatment dates back to the ancient Egyptians and Greeks. While it is often dismissed as quackery and pseudoscience by skeptics, proponents offer the theory that magnets may effect changes in cells or body chemistry, thus producing pain relief.

Narcotics (see Opioids, below).

Nerve blocks employ the use of drugs, chemical agents, or surgical techniques to interrupt the relay of pain messages between specific areas of the body and the brain. There are many different names for the procedure, depending on the technique or agent used. Types of surgical nerve blocks include neurectomy; spinal dorsal, cranial, and trigeminal rhizotomy; and sympathectomy, also called sympathetic blockade (see Nerve Blocks in the Appendix).

Nonsteroidal anti-inflammatory drugs (NSAIDs) (including aspirin and ibuprofen) are widely prescribed and sometimes called non-narcotic or non-opioid analgesics. They work by reducing inflammatory responses in tissues. Many of these drugs irritate the stomach and for that reason are usually taken with food. Although acetaminophen may have some anti-inflammatory effects, it is generally distinguished from the traditional NSAIDs.

Opioids are derived from the poppy plant and are among the oldest drugs known to humankind. They include codeine and perhaps the most well-known narcotic of all, morphine. Morphine can be administered in a variety of forms, including a pump for patient self-administration. Opioids have a narcotic effect, that is, they induce sedation as well as pain relief, and some patients may become physically dependent upon them. For these reasons, patients given opioids should be monitored carefully; in some cases stimulants may be prescribed to counteract the sedative side effects. In addition to drowsiness, other common side effects include constipation, nausea, and vomiting.

Physical therapy and rehabilitation date back to the ancient practice of using physical techniques and methods, such as heat, cold, exercise, massage, and manipulation, in the treatment of certain conditions. These may be applied to increase function, control pain, and speed the patient toward full recovery.

Placebos offer some individuals pain relief although whether and how they have an effect is mysterious and somewhat controversial. Placebos are inactive substances, such as sugar pills, or harmless procedures, such as saline injections or sham surgeries, generally used in clinical studies as control factors to help determine the efficacy of active treatments. Although placebos have no direct effect on the underlying causes of pain, evidence from clinical studies suggests that many pain conditions such as migraine headache, back pain, post-surgical pain, rheumatoid arthritis, angina, and depression sometimes respond well to them. This positive response is known as the placebo effect, which is defined as the observable or measurable change that can occur in patients after administration of a placebo. Some experts believe the effect is psychological and that placebos work because the patients believe or expect them to work. Others say placebos relieve pain by stimulating the brain's own analgesics and setting the body's self-healing forces in motion. A third theory suggests that the act of taking placebos relieves stress and anxiety-which are known to aggravate some painful conditions-and, thus, cause the patients to feel better. Still, placebos are considered controversial because by definition they are inactive and have no actual curative value.

R.I.C.E.-Rest, Ice, Compression, and Elevation-are four components prescribed by many orthopedists, coaches, trainers, nurses, and other professionals for temporary muscle or joint conditions, such as sprains or strains. While many common orthopedic problems can be controlled with these four simple steps, especially when combined with over-the-counter pain relievers, more serious conditions may require surgery or physical therapy, including exercise, joint movement or manipulation, and stimulation of muscles.

Surgery, although not always an option, may be required to relieve pain, especially pain caused by back problems or serious musculoskeletal injuries. Surgery may take the form of a nerve block (see Nerve Blocks in the Appendix) or it may involve an operation to relieve pain from a ruptured disc. Surgical procedures for back problems include discectomy or, when microsurgical techniques are used, microdiscectomy, in which the entire disc is removed; laminectomy, a procedure in which a surgeon removes only a disc fragment, gaining access by entering through the arched portion of a vertebra; and spinal fusion, a procedure where the entire disc is removed and replaced with a bone graft. In a spinal fusion, the two vertebrae are then fused together. Although the operation can cause the spine to stiffen, resulting in lost flexibility, the procedure serves one critical purpose: protection of the spinal cord. Other operations for pain include rhizotomy, in which a nerve close to the spinal cord is cut, and cordotomy, where bundles of nerves within the spinal cord are severed. Cordotomy is generally used only for the pain of terminal cancer that does not respond to other therapies. Another operation for pain is the dorsal root entry zone operation, or DREZ, in which spinal neurons corresponding to the patient's pain are destroyed surgically. Because surgery can result in scar tissue formation that may cause additional problems, patients are well advised to seek a second opinion before proceeding. Occasionally, surgery is carried out with electrodes that selectively damage neurons in a targeted area of the brain. These procedures rarely result in long-term pain relief, but both physician and patient may decide that the surgical procedure will be effective enough that it justifies the expense and risk. In some cases, the results of an operation are remarkable. For example, many individuals suffering from trigeminal neuralgia who are not responsive to drug treatment have had great success with a procedure called microvascular decompression, in which tiny blood vessels are surgically separated from surrounding nerves.

What is the Role of Age and Gender in Pain?

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.

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.

* Journal of the American Geriatrics Society (1998; 46:635-651).

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, 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.

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.

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.


Spine Basics: The Vertebrae, Discs, and Spinal Cord

Stacked on top of one another in the spine are more than 30 bones, the vertebrae, which together form the spine. They are divided into four regions:

  • the seven cervical or neck vertebrae (labeled C1-C7),
  • the 12 thoracic or upper back vertebrae (labeled T1-T12),
  • the five lumbar vertebrae (labeled L1-L5), which we know as the lower back, and
  • the sacrum and coccyx, a group of bones fused together at the base of the spine.

The vertebrae are linked by ligaments, tendons, and muscles. Back pain can occur when, for example, someone lifts something too heavy, causing a sprain, pull, strain, or spasm in one of these muscles or ligaments in the back.

Between the vertebrae are round, spongy pads of cartilage called discs that act much like shock absorbers. In many cases, degeneration or pressure from overexertion can cause a disc to shift or protrude and bulge, causing pressure on a nerve and resultant pain. When this happens, the condition is called a slipped, bulging, herniated, or ruptured disc, and it sometimes results in permanent nerve damage.

The column-like spinal cord is divided into segments similar to the corresponding vertebrae: cervical, thoracic, lumbar, sacral, and coccygeal. The cord also has nerve roots and rootlets which form branch-like appendages leading from its ventral side (that is, the front of the body) and from its dorsal side (that is, the back of the body). Along the dorsal root are the cells of the dorsal root ganglia, which are critical in the transmission of "pain" messages from the cord to the brain. It is here where injury, damage, and trauma become pain.

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.

Phantom Pain: How Does the Brain Feel?

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.

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.


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 (see The Nervous Systems). 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 (see The Nervous Systems) and may involve, for example, cutting a nerve that controls contraction of one or more arteries.
Author: National Institute of Neurological Disorders and Stroke


This guideline addresses the care of patients with acute pain after operation, medical procedures, or trauma. (Methods used to develop the guideline are in appendix A.) It outlines the physiological basis for pain and cites clinical studies linking effective postoperative pain management with improved patient outcomes. The guideline also describes practices that can minimize or eliminate acute pain. Rigid prescriptions for postoperative pain control are inappropriate because patients vary greatly in the severity of their preexisting pain, medical conditions, and pain experiences; the extensiveness of pathology and associated operations; responses to interventions; personal preferences; and the settings in which they receive care. Instead, this guideline offers clinicians a coherent yet flexible approach to pain assessment and management in daily practice. This guideline has four major goals:

  1. Reduce the incidence and severity of patients' postoperative or posttraumatic pain.
  2. Educate patients about the need to communicate unrelieved pain so they can receive prompt evaluation and effective treatment.
  3. Enhance patient comfort and satisfaction.
  4. Contribute to fewer postoperative complications and, in some cases, shorter stays after surgical procedures.

Need for Aggressive Postoperative Pain Control

Pain is an unpleasant sensory and emotional experience arising from actual or potential tissue damage or described in terms of such damage. No matter how successful or how deftly conducted, operations produce tissue trauma and release potent mediators of inflammation and pain .
Pain is just one response to the trauma of surgery, however. In addition to the major stress of surgical trauma and pain, the substances released from injured tissue evoke "stress hormone" responses in the patient. Such responses promote breakdown of body tissue; increase metabolic rate, blood clotting, and water retention; impair immune function; and trigger a "fight or flight" alarm reaction with autonomic features (e.g., rapid pulse) and negative emotions. Pain itself may lead to shallow breathing and cough suppression in an attempt to "splint" the injured site, followed by retained pulmonary secretions and pneumonia. Unrelieved pain also may delay the return of normal gastric and bowel function in the postoperative patient.

The physiological and psychosocial risks associated with untreated pain are greatest in frail patients with other illnesses such as heart or lung disease, those undergoing major surgical procedures such as aortic surgery, and the very young or very old. Because of advances in surgical and anesthetic techniques, it is now common for such patients to undergo operations once dismissed as prohibitively risky.

Approximately 23.3 million operations were performed in the United States in 1989, and most of these involved some form of pain management. Unfortunately, clinical surveys continue to show that routine orders for intramuscular injections of opioid "as needed" will leave more than half of postoperative patients with unrelieved pain due to undermedication. In the past, postoperative pain was thought to be inevitable, a harmless though intense discomfort that the patient had to tolerate. Unrelieved pain after surgery or trauma is often unhealthy; fortunately, it is preventable or controllable in an overwhelming majority of cases. Patients have a right to treatment that includes prevention or adequate relief of pain.

Recognition of the widespread inadequacy of pain management has prompted recent corrective efforts within multiple health care disciplines, including surgery. Although it is not practical or desirable to eliminate all postoperative pain, this clinical practice guideline sets forth procedures to minimize the incidence and severity of acute pain after surgical or medical procedures and trauma. The guideline is designed to help clinicians, patients, and patients' families understand the assessment and treatment of postoperative and other acute pain in both adults and children.

Health care is both a technical and an ethical enterprise. The ethical obligation to manage pain and relieve the patient's suffering is at the core of a health care professional's commitment. While medical treatments often involve risks and burdens, anything harmful to the patient, including postoperative pain, should be minimized or prevented if possible. The ethical importance of pain management is further increased when additional benefits for the patient are realized -- earlier mobilization, shortened hospital stay, and reduced costs. If inadequate pain management results from a clinician's conflict between reducing pain and avoiding potential side effects and/or legal liability, achieving greater technical competence and knowledge of risks and benefits can help to reduce such conflicts.

Prevention is Better than Treatment

Pain is dynamic. Without treatment, sensory input from injured tissue reaches spinal cord neurons and causes subsequent responses to be enhanced. Pain receptors in the periphery also become more sensitive after injury. Recent studies demonstrate long-lasting changes in cells within spinal cord pain pathways after a brief painful stimulus. Such physiological studies confirm longstanding clinical impressions that established pain is more difficult to suppress. The health care team should encourage patients to request pain medication before the pain becomes severe and difficult to control. Furthermore, the team should teach patients simple relaxation exercises to help decrease postoperative pain.

Aggressive pain prevention and control that occurs before, during, and after surgery can yield both short- and long-term benefits. In the very short term, for example, a patient's first request for analgesia after orthopedic surgery occurs later after operations performed with opioid premedication and intraoperative nerve blocks than after general anesthesia alone. In the short term, patients who undergo cesarean section under epidural anesthesia request less postoperative pain medication in the next 3 days than patients who have general anesthesia. Also in the short term, postoperative patients able to self-medicate with small intravenous doses of opioids such as morphine metered out by a programmable infusion pump -- patient controlled analgesia or PCA  -- have less pain and are more satisfied with their pain relief. These patients tend to be discharged earlier from the hospital compared with those given the same drug on an "as-needed" basis.
In the long term, after elective limb amputation for vascular insufficiency, patients who receive epidural analgesia before an operation are less likely to have chronic phantom limb pain, in contrast to those conventionally treated. Pilot studies such as these that show diverse benefits of aggressive pain treatment complement controlled clinical trials which indicate that postoperative morbidity and mortality decrease in high-risk populations such as the very young  or very old  when postoperative care includes aggressive pain relief.

Much of the clinical research cited here is preliminary and needs to be confirmed by properly designed clinical trials. Yet, when considered with laboratory reports and well-documented undertreatment of pain in hospitalized patients, it is likely that routine provision of proactive, aggressive pain treatment will benefit large numbers of postoperative patients. To ensure these benefits, institutions must develop and use formal procedures to assess pain and employ patient-based feedback to gauge the effectiveness of pain control(American Pain Society,).

Organization of the Guideline

To derive maximum benefit, clinicians should read the entire guideline. However, the guideline is organized so that users can go easily to those sections of immediate interest. Following a discussion of why clinicians should take an aggressive approach to prevention and control of postoperative pain, methods of pain assessment are described. Pharmacologic and nonpharmacologic methods of pain control are then presented for general control of postoperative pain, followed by discussion of pain control for specific operative sites and for specific types of patients. The final section discusses institutional responsibility for effective pain management. The appendixes contain a brief description of the methods used for scientific review and a table of scientific evidence for pain intervention, pain assessment tools, drug dosage tables for adults and children, and relaxation exercises.

Process of Pain Assessment and Reassessment

Pain is a complex, subjective response with several quantifiable features, including intensity, time course, quality, impact, and personal meaning. The reporting of pain is a social transaction between caregiver and patient. Therefore, successful assessment and control of postoperative pain depends in part on establishing a positive relationship between health care providers, patients, and (when appropriate) their families. Studies have shown that patients provided with information related to physiological coping (instruction in coughing, deep breathing, turning, and ambulation) reported less pain, were given fewer analgesics postoperatively, and had shorter lengths of stay . Egbert, Battit, Welch, and Bartlett (1964) found that providing patients sensory information preoperatively (i.e., detailed descriptions of discomforts to be expected postoperatively) decreased pain, analgesic use, and length of stay. Still other researchers found that patients provided with procedural and sensory information as well as instructions related to physiological coping tended to receive fewer analgesics  and had shorter lengths of stay than patients who were given less complete information.

As noted the subject of postoperative pain and its control is a critical part of the initial review of all relevant aspects of the planned procedure. The surgeon should discuss this with the patient and the family. In addition, pain assessment and management issues should be a part of the preoperative workups of the anesthesia and nursing staffs. Patients and their families should be informed that pain reports are valuable and important information, and also that pain may herald surgical complications that demand prompt diagnosis and therapy. To aid in planning and discussing pain control strategies with the patient, a member of the anesthesiology department should obtain a pain history during the preoperative visit. The pain history should include:

  • Significant previous and/or ongoing instances of pain and its effect on the patient;
  • Previously used methods for pain control that the patient has found either helpful or unhelpful;
  • The patient's attitude toward and use of opioid, anxiolytic, or other medications, including any history of substance abuse;
  • The patient's typical coping response for stress or pain, including more broadly, the presence or absence of psychiatric disorders such as depression, anxiety, or psychosis;
  • Family expectations and beliefs concerning pain, stress, and postoperative course;
  • Ways the patient describes or shows pain; and
  • The patient's knowledge of, expectations about, and preferences for pain management methods and for receiving information about pain management.

Some patients fear overmedication (e.g., "They will medicate me into oblivion so that I won't be any trouble"). Others know from previous experience that they are prone to side effects of certain drugs (e.g., dysphoria or nausea). Patients who express fears or concerns related to previous analgesic effects may require a cautious approach to medication. Preoperative anxiety may indicate a concurrent medical condition such as substance abuse or withdrawal, hyperthyroidism, anxiety disorder, affective disorder, psychosis, or a medication side effect. Excessive preoperative anxiety should be assessed and a psychiatric or psychologic consultation considered to assist with perioperative management. When the preoperative assessment is complete, the health care team should develop a pain management plan in collaboration with the patient. When developing the pain management plan, clinicians must consider the relative risks, benefits, and costs of available pain control options. They also should attempt to correct patient misconceptions about the use of pharmacologic or nonpharmacologic strategies.

Once a pain management plan is in place, preoperative preparation of the patient and family is extremely important. Preoperative preparation of patients (and families, when appropriate) assists patients in understanding their responsibilities in pain management. To ensure that postoperative pain measurement is both valid and reliable, the staff should review the selected pain measurement tool -- for example, a simple descriptive scale or a visual analog scale -- with the patient before surgery. Pain assessment instruments are discussed below and samples are provided in appendix D. The patient should be told how frequently pain will be assessed and asked to select a measurement tool. A member of the health care team should advise the patient that a score above some predetermined criterion of the patient's choosing (e.g., a score of 3-4 on a 10-point scale) will result in a dose increment or other intervention. The patient's negotiation of this criterion is particularly important if the patient fears overmedication or intends to cope psychologically with the pain. Patient preferences should be supported.

Assessment of pain after surgery should be frequent and simple. Many different measurement tools are available, and several factors help determine the best choices. First, consider the patient's age; developmental status; physical, emotional, or cognitive condition; and preference. Second, consider the expertise, time, and effort available from the individual performing the assessment. Third, examine the institution's requirements for monitoring and documentation for quality assurance purposes. Based on these factors, each health care institution should educate staff in the proper and consistent use of a valid assessment tool(s) and establish its own quality assurance program for evaluation of postoperative pain assessment and management (American Pain Society, For example, recording pain intensity on the bedside vital sign chart may be considered necessary to make the assessment easily accessible to members of the health care team. In addition, each institution should identify individuals responsible for postoperative pain assessment and control.
The single most reliable indicator of the existence and intensity of acute pain -- and any resultant affective discomfort or distress -- is the patient's self-report.

A comprehensive approach to postoperative pain assessment requires evaluation of: 1) patient perceptions; 2) physiological responses; 3) behavioral responses; and 4) cognitive attempts by the patient to manage pain. Physiological responses such as heart rate, blood pressure, and respiratory rate provide critical information in the immediate postoperative period. Once the patient has recovered from anesthesia, the mainstay of pain assessment should be the patient's self-report to assess pain perceptions (including description, location, intensity/severity, and aggravating, and relieving factors) and cognitive response. Patient self-report is the single most reliable indicator of the existence and intensity of acute pain and any concomitant affective discomfort or distress . Neither behavior nor vital signs can substitute for a self-report. Patients may be experiencing excruciating pain even while smiling and using laughter as coping mechanisms.

Samples of commonly used pain assessment tools are in appendix D. Three common self-report measurement tools useful for assessment of pain intensity and affective distress in adults and many children are: 1) a numerical rating scale (NRS); 2) a visual analog scale (VAS); and 3) an adjective rating scale (ARS). While many researchers prefer visual analog measures, each of these tools can be a valid and reliable instrument as long as end points and adjective descriptors are carefully selected.

In practical use, the visual analog scale is always presented graphically, usually with a 10-cm baseline and endpoint adjective descriptors. Patients place a mark on the line at a point that best represents their pain. The visual analog scale is scored by measuring the distance of a patient's mark from the zero. The numerical and adjective rating scales may be presented graphically (see appendix D) or in other formats. For example, numerical rating scales are sometimes presented verbally, and adjective rating scales are presented as a list of pain descriptors. In a graphic format, scoring of the numerical and adjective rating scales may be the same as that described above for the visual analog scale, or they can be scored as numeric integers.

For each of these scales, the clinician should request the patient's self- report, not only with the patient at rest but also during routine activity such as coughing, deep breathing, or moving (e.g., turning in bed). Complaints of pain must be heeded. The patient should be observed for behaviors that often indicate pain, such as splinting the operative site, distorted posture, impaired mobility, insomnia, anxiety, attention seeking, and depression. Patient awareness of pain and the ability to control pain are important components of pain assessment. If pain behavior is observed or if the patient expresses feelings of inadequate control, a member of the health care team should discuss these with the patient and share this information with other members of the team. The management plan should then be revised as needed.

The clinician should document the patient's preferred tool for pain assessment and the goal for postoperative pain control as expressed by a score on a pain scale in the patient's chart as part of the pain history. Simply to record patient responses to the question "how is your pain?" invites misunderstanding or denial and hinders quantification. Pain should be assessed and documented: 1) preoperatively; 2) routinely at regular intervals postoperatively, as determined by the operation and severity of the pain (e.g., every 2 hours while awake for 1 day after surgery); 3) with each new report of pain; and 4) at a suitable interval after each analgesic intervention (e.g., 30 minutes after parenteral drug therapy, and 1 hour after oral analgesics). Most important, the team should evaluate immediately each instance of unexpected intense pain, particularly if sudden or associated with oliguria or altered vital signs such as hypotension, tachycardia, or fever, and consider new diagnoses such as wound dehiscence, infection, or deep venous thrombosis.

Each instance of unexpected intense pain, particularly if sudden or associated with oliguria or altered viatl signs such as hypotension, tachycardia, or fever, should be immediately evaluated to consider new diagnoses such as wound dehiscence, infection, or deep venous thrombosis.

Occasionally, apparent discrepancies between behaviors and a patient's self-report of pain may occur. For example, patients may describe pain as an 8 out of 10 on a pain scale while smiling and walking freely or as 2 out of 10 while tachycardic, splinting, and sweating. Discrepancies between behavior and a patient's self-report may result from excellent coping skills. The patient who uses distraction and relaxation techniques may engage in diversionary activities while still experiencing severe pain. Patients may deny severe pain for a variety of reasons, including fear of inadequate pain control or a perception that stoicism is expected or rewarded. Similarly, patients managed with as- needed analgesia may perceive that medication will be given only if the pain score is very high. Patients who perceive staff as inattentive to their concerns may use pain as a way to get help for other reasons.

When discussing pain assessment and control with patients, members of the health care team should emphasize the importance of a factual report, thereby avoiding both stoicism and exaggeration. Patients with anxiety or other concerns should rate their mood and emotional distress separately from their pain by using similar scales (see Pain Distress Scales in appendix D). When discrepancies between behaviors and self- reports of pain occur, clinicians should address these differences with the patient. The team and the patient should then renegotiate the pain management plan.
Patients unable to communicate effectively with staff require special consideration for pain assessment, e.g., neonates and children, developmentally delayed persons, psychotic patients, patients with dementia, and non-English speaking patients. Children and cognitively impaired patients require simpler or modified pain measurement scales and assessment approaches (see section on pain in children). The staff should work with both the patient and parent or guardian pre- and postoperatively. Staff should endeavor to find a translator for the non-English speaking patient, at least once, to determine a convenient way to assess pain. Members of the health care team should attend to the preferences and needs of patients whose education or cultural tradition may impede effective communication.

Certain cultures have strong beliefs about pain and its management, and these patients may hesitate to complain about unrelieved pain. Such beliefs and preferences should be determined and respected, if at all possible.In summary, health care providers should view good pain control as a source of pride and a major responsibility in quality care. Support personnel otherwise untrained in pain assessment should be encouraged to be "pain vigilant" and report to the health care team any patient discomfort, such as during transport or transfer to an x-ray table. At the institutional level, periodic evaluation studies should be conducted to monitor the effectiveness of pain assessment and management procedures. Without institutional support for an organized process by which pain is recognized, documented, assessed, and reassessed on a regular basis, staff efforts to treat pain may become sporadic and ineffectual.

A pain care process relying on patients' or families' demands for analgesia "as needed" will produce intervals of inadequate pain control and worsen burdens of anxiety, loss of personal control, sleeplessness, and fatigue after surgery. Patients and their families should understand that pain relief is an important part of their health care, that information about options to control pain is available, and that they are welcome to discuss their preferences with the health care team. Patients should recognize that health professionals will elicit and respond quickly to their pain reports. Before a patient's discharge, those taking care of the patient should describe the interventions used to manage pain and assess their effectiveness. This review, while good practice for each patient, is especially important when initial management was unsuccessful and/or when side effects or other complications occurred.

Options to Prevent and Control Postoperative Pain

Patient education and reduction of any preexisting pain should occur before the operation. Because the goal of the treatment plan is to prevent significant postoperative pain from the outset, treatment alternatives, potential risks, dosage adjustments, and adjunctive therapies should be described to the patient and family. Teaching emphasizes what the patient is likely to experience postoperatively, including the specific method(s) of pain assessment, intervention(s) the staff will employ, and the level of patient participation required. Staff also should inform patients that it is easier to prevent pain than to "chase" or treat it once it has become established, and that communication of unrelieved pain is essential to its relief.
Pain control options include:

  • Cognitive-behavioral interventions such as relaxation, distraction, and imagery; these can be taught preoperatively and can reduce pain, anxiety, and the amount of drugs needed for pain control;
  • Systemic administration of nonsteroidal anti-inflammatory drugs (NSAIDs) or opioids using the traditional "as needed" schedule or around-the-clock administration ;
  • Patient controlled analgesia (PCA), usually meaning self-medication with intravenous doses of an opioid; this can include other classes of drugs administered orally or by other routes;
  • Spinal analgesia, usually by means of an epidural opioid and/or local anesthetic injected intermittently or infused continuously;
  • Intermittent or continuous local neural blockade (examples of the former include intercostal nerve blockade with local anesthetic or cryoprobe; the latter includes infusion of local anesthetic through an interpleural catheter);
  • Physical agents such as massage or application of heat or cold; and
  • Electroanalgesia such as transcutaneous electrical nerve stimulation (TENS).

A postoperative pain management plan might include several of these options. A pamphlet, or "menu" of alternative strategies, can help focus discussion of these options between caregivers and the patient. The postoperative pain management plan should reflect coexisting and/or ongoing problems such as cancer-related pain or opioid tolerance. The plan should be consistent with the overall surgical and anesthetic plans. For example, an elixir form of analgesic is preferable to a tablet when painful or difficult swallowing is anticipated. Also, if the patient is to have an epidural catheter placed during surgery that could make postoperative pain control simpler or more effective, it should not be removed in the Post-Anesthesia Care Unit (PACU).

Staff should note their plans for pre-, intra-, and postoperative pain management in the patient's chart so that other members of the care team can respond to patient questions and coordinate plans for rehabilitation and discharge.

Intraoperative management is often key to the success of postoperative pain control. If pain prevention and control are to be achieved through an epidural catheter, the catheter should be placed and its function verified preoperatively to assure its effective intra- and postoperative use. This is particularly true in patients whose position, body casts, or subsequent anticoagulation make postoperative catheter insertion problematic. The planned pre- and intraoperative use of opioids, and timing of the first postoperative opioid dose by the anesthesiologist, nurse anesthetist, surgeon, or PACU nurse are important in the postoperative care plan. Equally important are decisions during surgery on the concurrent use of local anesthetics (e.g., for intraoperative nerve blocks) and the nature of the surgical incision and placement of drains or tubes (e.g., chest, and nasogastric). If TENS is to be used for postoperative pain management, the electrodes may need to be placed intraoperatively. Finally, intraoperative placement of casts and splints to provide support and restrict postoperative movement may enhance other pain management efforts.

Pharmacologic Management

Pharmacologic management of mild to moderate postoperative pain should begin, unless there is a contraindication, with an NSAID. Moderately severe to severe pain normally should be treated initially with an opioid analgesic. After many relatively noninvasive surgical procedures, NSAIDs alone can achieve excellent pain control. NSAIDs decrease levels of inflammatory mediators generated at the site of tissue injury. Even when insufficient alone to control pain, NSAIDs have a significant opioid dose-sparing effect upon postoperative pain and can be useful in reducing opioid side effects. The concurrent use of opioids and NSAIDs often provides more effective analgesia than either of the drug classes alone. Although it is likely that NSAIDs also act within the central nervous system, in contrast to opioids, they do not cause sedation or respiratory depression, nor do they interfere with bowel or bladder function. Acetaminophen does not affect platelet aggregation, nor does it provide peripheral anti- inflammatory activity. Some evidence exists that two salicylates do not affect platelet aggregation profoundly; these are salsalate and choline magnesium trisalicylate. All other NSAIDs appear to produce a risk of platelet dysfunction that may impair blood clotting and carry a small risk of gastrointestinal bleeding. At present, one NSAID (ketorolac) is approved by the Food and Drug Administration for parenteral use. The analgesic dosage tables in appendixes B and C include information on NSAIDs, opioids, and other analgesic drugs.

Opioid analgesics are the cornerstone of pharmacological postoperative pain management, especially for more extensive surgical procedures that cause moderate to severe pain. Other agents such as NSAIDs or single injections of local anesthetics may control mild to moderate pain after relatively minor procedures or reduce opioid dose requirements after more extensive operations when this is a goal. Even in the absence of preemptive efforts targeted at postoperative analgesia, adequate postoperative pain control can usually be achieved with opioid analgesics. When increasing doses of opioids are ineffective in controlling postoperative pain, a prompt search for residual pathology is indicated, and other diagnoses such as neuropathic pain should be considered.
Opioid tolerance or physiological dependence is unusual in short-term postoperative use in opioid naive patients. Likewise, psychologic dependence and addiction are extremely unlikely to develop after patients without prior drug abuse histories use opioids for acute pain. Proper use of opioids involves selecting a particular drug and route of administration and judging: 1) suitable initial dose; 2) frequency of administration; 3) optimal doses of non- opioid analgesics, if these are also to be given; 4) incidence and severity of side effects; and 5) whether the analgesic will be given in an inpatient or ambulatory setting. Titration to achieve the desired therapeutic effect in the immediate postoperative period and to maintain that effect over time should be emphasized.

Opioids produce analgesia by binding to opioid receptors both within and outside the central nervous system. Opioid analgesics are classified as full agonists, partial agonists, or mixed agonist-antagonists, depending on the manner in which they interact with opioid receptors. Full agonists produce a maximal response within the cells to which they bind; partial agonists produce a lesser response, regardless of their concentration; and mixed agonist- antagonists activate one type of opioid receptor while simultaneously blocking another type. Several types and subtypes of such receptors exist. The most important receptor type for clinical analgesia is named "mu" because of its affinity for morphine. Other commonly used mu opioid agonists include hydromorphone, codeine, oxycodone and hydrocodone, methadone, levorphanol, and fentanyl. All mu opioid agonists have the potential to cause constipation, urinary retention, sedation, and respiratory depression and frequently also produce nausea or confusion. Mixed agonist- antagonists in clinical use include pentazocine [Talwin], butorphanol tartrate [Stadol], and nalbuphine hydrochloride [Nubain]; each of these blocks or is neutral at the mu opioid receptor while simultaneously activating a different type of opioid receptor termed "kappa." Patients receiving mu opioid agonists should not be given a mixed agonist- antagonist because doing so may precipitate a withdrawal syndrome and increase pain. Mixed agonist-antagonists and partial agonists may exhibit a ceiling effect not only with respect to respiratory depression  but also in regard to their analgesic activity. In the awake patient, there is a clinical ceiling analgesic effect even with morphine because side effects such as respiratory depression limit the dose that may be safely given. However, this does not limit the ability of clinicians to effectively increase the drug dose when the painful stimulus increases and respiratory status is monitored.

Meperidine [Demerol], a mu opioid analgesic, is commonly used for postoperative pain control. Meperidine is commonly underdosed and administered too infrequently even by physicians aware of its pharmacokinetics. The common postoperative meperidine order of 75 mg parenterally every 4 hours as needed often is inadequate for several reasons. Meperidine produces clinical analgesia for only 2.5-3.5 hours, and a dose of 75 mg every 4 hours is equivalent to only 5- 7.5 mg of morphine. Therefore, to obtain postoperative analgesia equal to that from 10 mg of morphine sulfate every 4 hours, a clinician would have to use 100-150 mg of meperidine every 3 hours. Because of its unique toxicity, meperidine is often contraindicated in patients with impaired renal function and those receiving antidepressants of the monamine oxidase inhibitor class . Normeperidine (6-N-desmethylmeperidine) is a toxic meperidine metabolite excreted through the kidney. In patients with normal renal function, normeperidine has a half-life of 15 to 20 hours; this time is extended greatly in elderly individuals and patients with impaired renal function. Normeperidine is a cerebral irritant that can cause effects ranging from dysphoria and irritable mood to convulsions. These effects have been observed even in young, otherwise healthy patients given sufficiently high doses of normeperidine postoperatively. Therefore, meperidine should be reserved for very brief courses in otherwise healthy patients who have demonstrated an unusual reaction (e.g., local histamine release at the infusion site) or allergic response during treatment with other opioids such as morphine or hydromorphone.

Titration of opioids should be based on the patient's analgesic response and side effects. Remember that patients vary greatly in their analgesic dose requirements and responses to opioid analgesics. Relative potency estimates provide a rational basis for selecting the appropriate starting dose to initiate analgesic therapy, changing the route of administration (e.g., from parenteral to oral), or when switching to another opioid. Dosage conversion factors based on relative potency estimates may differ somewhat between individual patients. When estimating the initial postoperative dose of an opioid analgesic, a clinician should consider whether patients have been receiving opioid analgesics preoperatively. In such patients, supplemental postoperative doses should be adjusted above the preoperative baseline requirement unless the operation itself is likely to remove the painful stimulus.

An "as-needed" order for opioid administration can result in prolonged delays while the nurse unlocks the controlled substances cabinet and prepares the drug for administration and until the drug takes effect. These delays can be eliminated by administering analgesics on a regular time schedule initially. For example, if the patient is likely to have pain requiring opioid analgesics for 48 hours following surgery, morphine could be ordered every 4 hours by the clock (not "as needed") for 36 hours. Once the duration of analgesic action is determined for a patient, the dosage frequency should be adjusted to prevent pain from recurring. Depending on patient preferences, the orders may be written so that the patient can refuse an analgesic if not in pain or forego it if asleep. However, as in dosing with other drugs that require a steady blood level to remain effective, interruption of an around-the-clock dosage schedule during the hours of sleep may cause the patient to be suddenly awakened by intense pain as blood analgesic levels decline.

It may be acceptable late in the postoperative course to give the same drug every 4 hours as requested. Switching from an around-the-clock to an as- needed dosage schedule later in the patient's course is one way to provide pain relief while minimizing the risk of adverse effects as the patient's analgesic dose requirement diminishes. As part of this schedule, a patient's pain should be assessed at regular intervals to determine the efficacy of the drug intervention, the presence of side effects, or the need for dosage adjustment or supplemental doses for breakthrough pain. Effective use of opioid analgesics should facilitate routine postoperative activities -- e.g., coughing and deep breathing exercises, ambulation, and physical therapy. The opioid should be withheld if the patient is sedated when awake or whenever there is respiratory depression (usually fewer than 10 breaths per minute).

Opioids may be administered by a variety of routes; oral dosing is usually the most convenient and least expensive route of administration. It is appropriate as soon as the patient can tolerate oral intake and is the mainstay of pain management in the ambulatory surgical population.
Preoperative intravenous or epidural access may be appropriate for postoperative management of severe pain, even when the oral route is available. Relatively few side effects will occur ordinarily, providing that these modalities are carefully managed by clinicians with appropriate expertise. Using potent analgesics or invasive techniques postoperatively, at a time when a patient's level of consciousness and physical function are returning to normal, requires careful titration and patient assessment.

Drug dosage, frequency, side effects, and risks differ even more noticeably between the intravenous and epidural routes than between the oral and intravenous routes. Clinicians not familiar with epidural opioid doses and pharmacokinetics must review the literature carefully before using that route. In addition, side effects (e.g., confusion, respiratory depression, hypotension, urinary retention, or pruritus) associated with opioids can be greater with intravenous and epidural administration and require ongoing assessment and monitoring. Other potential problems that dictate expert vigilance and followup during epidural analgesia include abscess development or anesthesia of a nerve root at the site of catheter tip.

These routes of administration are best limited to specially trained staff who are knowledgeable and skilled in the management of patients receiving intravenous or epidural opioids, typically under the direction of an acute or postoperative pain treatment service.

Patient controlled analgesia is a safe method for postoperative pain management that many patients prefer to intermittent injections. Systemic PCA usually connotes intravenous drug administration, but it also can be subcutaneous or intramuscular. Few studies of the use of PCA drug delivery to the epidural space exist. A typical intravenous PCA prescription applicable to many contexts relies on a series of "loading" doses; for example, 3-5 mg of morphine, repeated every 5 minutes until the initial postoperative pain (if present) diminishes. A low-dose basal infusion (0.5-1 mg/hr) at night allows uninterrupted sleep. On-demand doses typically add 1 mg of morphine every 6 minutes, with a total hourly limit of 10 mg. Once the patient is able to take oral medications, an around-the-clock schedule of an oral opioid such as a codeine-acetaminophen combination is provided, and the basal infusion rate is discontinued. By observing the number of "on-demand" doses self- administered by the patient, the clinician can assess the adequacy of the oral medication and titrate it further, change to a stronger compound such as oxycodone with acetaminophen, or discontinue the PCA pump.

Intravenous administration is the preferred route for postoperative opioid therapy when the patient cannot take oral medications. When intravenous access is problematic, sublingual and rectal routes should be considered as alternatives to traditional intramuscular or subcutaneous injections. All routes other than intravenous require a lag time for absorption of the drug into the circulation. In addition, repeated injections with associated pain and trauma may deter some patients, especially children, from requesting pain medication. Continuous administration of low doses of opioids intravenously or transdermally and intermittent delivery across the buccal mucosa are relatively new but apparently effective methods to administer opioids postoperatively. Further experience is needed to define the clinical roles of these innovative methods in relation to more well-established methods.

Patient controlled analgesia (PCA) is a safe method for postoperative pain management that many patients prefer to intermittent injections.

Opioids and local anesthetic agents interact favorably. Continuous administration into the epidural space of low concentrations of opioids in dilute solutions of local anesthetic provides excellent analgesia, while reducing the potential risks (e.g., respiratory depression or motor block) associated with equianalgesic concentrations of either agent administered singly. In a less technologically demanding approach, systemically administered opioids given pre-, intra-, or postoperatively augment the duration and effectiveness of local anesthetics given spinally or epidurally. Local anesthetics alone may be applied intermittently to specific nerves to interrupt pain pathways. For example, injecting local anesthetics around the intercostal nerves after thoracotomy significantly improves pulmonary function. Catheters for continuous or repeated intermittent dosing of local anesthetic also have been employed postoperatively in the pleural space or adjacent to nerves such as the brachial plexus or cervical sympathetic ganglia. However, a clinical role for interpleural or perineural local anesthetics in the postoperative setting has not yet been defined.

Nonpharmacologic Management

Nonpharmacologic interventions can be classified as either cognitive- behavioral interventions or physical agents. Cognitive and behaviorally based approaches include several ways to help patients understand more about their pain and take an active part in its assessment and control. The goals of interventions classified as cognitive-behavioral therapies are to change patients' perceptions of pain, alter pain behavior, and provide patients with a greater sense of control over pain. The goals of interventions classified as physical agents or modalities are to provide comfort, correct physical dysfunction, alter physiological responses, and reduce fears associated with pain-related immobility or activity restriction. Nonpharmacologic approaches are intended to supplement, not substitute for, the pharmacologic or invasive techniques described above.

Nonpharmacologic interventions are appropriate for the patient who: 1) finds such interventions appealing; 2) expresses anxiety or fear, as long as the anxiety is not incapacitating or due to a medical or psychiatric condition that has a more specific treatment; 3) may benefit from avoiding or reducing drug therapy (e.g., history of adverse reactions, fear of or physiological reason to avoid oversedation); 4) is likely to experience and need to cope with a prolonged interval of postoperative pain, particularly if punctuated by recurrent episodes of intense treatment- or procedure-related pain; or 5) has incomplete pain relief following appropriate pharmacologic interventions. Cognitive- behavioral approaches include preparatory information, simple relaxation, imagery, hypnosis, and biofeedback. Physical therapeutic agents and modalities include application of superficial heat or cold, massage, exercise, immobility, and electroanalgesia such as TENS therapy.
Giving a patient a detailed description of all medical procedures, expected postoperative discomfort, and instruction aimed at decreasing treatment- and mobility-related pain can decrease self-reported pain, analgesic use, and postoperative length of stay.

Patients should receive sufficient procedural and sensory information to satisfy their interest and enable them to assess, evaluate, and communicate postoperative pain. In addition, all preoperative patients should receive instruction emphasizing the importance of coughing, deep breathing, turning, and walking, along with suggestions on how to decrease physical discomforts from such activities. When fear or anxiety occur, it is important to assess psychological coping skills and provide practical suggestions for managing pain and maintaining a positive outlook. Patients who appear anxious or fearful before surgery, and others who express an interest in cognitive-behavioral strategies, should be assisted in selecting an intervention (e.g., simple relaxation or imagery) and taught how to use it. In some patients, particularly those with high levels of anxiety, too much information, or too many demanding decisions can exacerbate fear and pain. Psychiatric evaluation is appropriate for patients who manifest disabling or disruptive anxiety symptoms such as emotional instability, restlessness, inability to sleep, and dulled thinking.

Relaxation is the most widely evaluated cognitive-behavioral approach to postoperative pain management. Relaxation strategies, including simple relaxation, have all shown some degree of effectiveness in reducing pain. Relaxation strategies and imagery techniques need not be complex to be effective. Relatively simple approaches such as the brief jaw relaxation procedure described on page 25 have been successful in decreasing self- reported pain and analgesic use. These strategies take only a few minutes to teach but require periodic reinforcement through encouragement and coaching. Supportive family members or audiotapes often can sustain patient skills. [Sample relaxation and imagery exercises are included in appendix B and printed resource materials or manuals are available elsewhere.]

A relaxation strategy that can be used informally is music distraction. Both patients' personally preferred music  and "easy listening" music  have significantly decreased postoperative pain in clinical studies. Patients who need repeated coaching may benefit from the use of a commercially prepared relaxation or music- assisted relaxation audiotape.
Other cognitive-behavioral strategies require greater professional involvement; these include complex imagery, hypnosis, biofeedback, and combined therapies. Such strategies are commonly applied when patients have chronic pain even before surgery.

Examples of Nonpharmacologic Interventions for Postoperative Pain


Physical Agents


Applications of heat or cold


Massage, exercise, and immobilization


Music distraction

Transcutaneous electrical nerve stimulation


Jaw Relaxation Instructions

  • Let your lower jaw drop slightly, as though you were starting a small yawn.
  • Keep your tongue quiet and resting on the bottom of your mouth.
  • Let your lips get soft.
  • Breathe slowly, evenly, and rhythmically: inhale, exhale, and rest.
  • Allow yourself to stop forming words with your lips and stop thinking in words.

Although some data suggest that the use of complex imagery may reduce pain, that biofeedback may lessen pain and operative site muscle tension, and that interventions which combine imagery and relaxation may decrease pain, each requires specialized training and, for biofeedback, the use of special equipment. Findings from studies of hypnosis for control of postoperative pain are inconsistent. Insufficient research to demonstrate effectiveness in reducing postoperative pain and the need for special training or equipment preclude the recommendation of complex imagery, biofeedback, or hypnosis for routine postoperative pain control. This is not to say that patients who have a high level of preoperative anxiety, whose pain is severe and enduring, or who suffer recurrent episodes of procedure-related pain will not benefit from these strategies. However, for such patients a more comprehensive pain management program must include active involvement of professionals skilled in cognitive-behavioral therapy and psychological assessment.

In addition to cognitive-behavioral interventions, several physical therapeutic methods can be used to manage pain . Commonly used physical agents include applications of heat and cold, massage, exercise, and rest or immobilization. Applications of heat or cold are used to alter pain threshold, reduce muscle spasm, and decrease congestion in an injured area. Applications of cold are used initially to decrease tissue injury response. Later, heat is used to facilitate clearance of tissue toxins and accumulated fluids. Massage and exercise are used to stretch and regain muscle and tendon length. Immobilization is used following many musculoskeletal procedures to provide rest and maintain the alignment necessary for proper healing. With the exception of applications of cold and immobilization, these interventions typically are not used following surgery unless complications occur or an extended postoperative course is expected. When physical modalities are used, it is often for a physiological goal other than pain relief. Of these modalities only cryotherapy (application of cold) has been evaluated in the literature. Lanham and colleagues (1984) and Rooney and colleagues (1986) used cryotherapy in association with TENS therapy. There is insufficient evidence to suggest that cryotherapy alone is effective in reducing postoperative pain. Cryotherapy is different from cryoanalgesia (application of a cryoprobe to specific peripheral nerves), which has proven effective for post- thoracotomy pain.

TENS therapy is one physical modality for which there is some support. TENS therapy has been effective in reducing self-reported pain and analgesic use following abdominal surgery, orthopedic surgery, thoracic surgery, mixed surgical procedures, and cesarean section. TENS therapy also has improved physical mobility following thoracic  and orthopedic  surgery. Both TENS therapy and sham TENS therapy (that is, application of electrodes without transmission of electric current) significantly reduced analgesic use and subjective reports of pain. No significant differences were found between TENS therapy and sham-TENS. Even though these findings suggest a placebo effect underlies the reduction of perceived pain and analgesic use during TENS therapy, beneficial effects do, in fact, result. The physical modalities of acupuncture and electroacupuncture also have been clinically evaluated in postoperative patients, with conflicting findings; no clear analgesic effect has been demonstrated.

How each patient's postoperative pain management program is designed and implemented will vary according to the type of medical facility and services available to support a pain management program. At the least, clinicians should be introduced to these methods so they recognize the benefits of cognitive-behavioral and physical interventions, know the indications for their use, and are able to provide information and counseling to patients. In addition, patients should have access to written information about available therapies, why and when to use them, and sources for self- management materials or professional consultations.

Catastrophic postoperative events are rarely, if ever, masked by any of the approaches to postoperative pain control previously described. Any sudden or unexplained change in pain intensity requires immediate evaluation by the surgeon. Likewise, a sudden increase in anxiety may signal cardiac or pulmonary decompensation and requires prompt medical or surgical assessment.

Process of Effective Pain Management

Postoperative pain management

As illustrated the process of postoperative pain management is ongoing. Following intraoperative anesthesia and analgesia, postoperative pain assessment and management begin. Based on the preoperative plan, postoperative drug and nondrug interventions are initiated. Patients should be reassessed at frequent intervals (not less than every 2-4 hours for the first 24 hours) to determine the efficacy of the intervention in reducing pain. If the intervention is ineffective, additional causes of pain should be considered, the plan should then be reevaluated, and appropriate modifications should be made. Pharmacologic interventions should be titrated to achieve optimal pain control with minimal adverse effects. Ongoing reassessment ensures satisfactory pain relief with the most appropriate balance of drug and nondrug strategies.

Discharge planning

Inpatients, as well as ambulatory surgical patients, should be given a written pain management plan at discharge. Pertinent discharge instructions related to pain management include: specific drugs to be taken; frequency of drug administration; potential side effects of the medication; potential drug interactions; specific precautions to follow when taking the medication (e.g., physical activity limitations, dietary restrictions); and name of the person to notify about pain problems and other postoperative concerns.

Site-Specific Pain Control

Even for a single operation, there may be great variability in the approach to postoperative pain management based on patient factors such as age, weight, ability to understand and cooperate with plans for care, coexisting medical and psychological problems, and idiosyncratic sensitivity to analgesics; intraoperative course, such as size and location of incisions or drain placement or anesthetic management; and institutional resources available for specialized treatment and monitoring in the particular setting.

Despite these variable factors, the clinician can still outline certain pain management options to present to an adult patient whose management is otherwise uncomplicated. Many aspects of pain control are shared between operations on different parts of the body. For practical reference, pain management options for various surgical procedures are presented according to region of the body rather than by the pathophysiological mechanisms involved. In all cases, however, preoperative psychological preparation and medication should be considered, and ongoing postoperative assessment and reassessment of pain should be routine. In this way, pain can be controlled effectively. Vigilance for changes in postoperative pain will trigger prompt searches for diagnostically significant causes of new pain.

Head and Neck Surgery

The most common forms of dental surgery are brief and relatively noninvasive procedures often performed on an outpatient basis. A patient's anxiety is frequently disproportionate to the safety of the procedure; such a patient may benefit from behavioral or pharmacologic (anxiolytic) therapy. Mild pain associated with most forms of uncomplicated dental care such as simple tooth extractions, endodontic therapy, or scaling of the periodontal area or of a previously asymptomatic tooth is well managed by oral administration of an NSAID such as aspirin or ibuprofen. Preoperative administration of ibuprofen appears to delay the onset of postoperative pain and lessen its severity. For patients unable to tolerate aspirin or ibuprofen, acetaminophen can provide an acceptable analgesic effect.

Dental procedures such as surgical removal of bony impactions and osseous periodontal surgery are more traumatic and typically produce intense and prolonged postoperative pain. The onset of such pain can be delayed by preoperative treatment with ibuprofen and/or application of a long-acting local anesthetic such as bupivacaine during the procedure.

Rarely, an intravascular or intraneural injection of local anesthetic in this context leads to bruising, bleeding, or systemic symptoms such as fainting, allergic reaction, or persistent pain due to direct nerve injury. When postoperative pain does emerge, it often requires the addition of an opioid to the nonsteroidal regimen. Codeine is frequently prescribed at a dosage of 30- 60 mg every 4-6 hours. Increased analgesia -- but also an increased number of opioid side effects such as nausea, constipation, sedation, and respiratory depression -- follow dosage increases above this level. Alternative opioids include propoxyphene or oxycodone administered in doses that are equianalgesic to 30-60 mg of codeine.

Some operations on the oral cavity preclude the patient's taking oral medications postoperatively (e.g., wiring the mouth closed after an operation on a mandibular fracture). Alternative therapy should be based on the severity of the surgical procedure and expected pain associated with it, as well as the surroundings in which it will be managed. Formulations of NSAIDs such as rectal suppositories (indomethacin) or intramuscular injection (ketorolac) are now commonly available. Opioids may be administered by a variety of routes (intravenous, intramuscular, subcutaneous injection, transdermal, rectal) and schedules, including a patient controlled schedule. Cost-efficacy analyses of parenteral opioid administration for oral surgery are not sufficient to permit any clear recommendations. Pain that does not respond to these measures should prompt a search for infection, osteitis, peripheral nerve injury, or the emergence of psychological and behavioral changes consistent with the development of chronic pain syndrome.

Radical head and neck surgery

These operative procedures commonly interfere with oral intake for prolonged periods postoperatively and may be combined with a feeding gastrostomy or jejunostomy. Airway patency is always a consideration in these patients, and a tracheostomy frequently is an integral part of the operation. The use of flap coverage or skin grafts further increases the number of potentially painful sites. Prolonged preoperative pain, radiotherapy, and chemotherapy are important preoperative modifiers of pain therapy. Thus, the very nature of the operative procedure may dictate alternate routes for pain therapy in patients who have undergone major head and neck ablative procedures that may interfere with a patient's ability to describe pain and his or her response to analgesic intervention.

Intraoperative positioning of the head and neck are critical. Protective padding and avoidance of extreme flexion, extension, and rotation may help obviate or minimize muscle spasm-induced pain after surgery. Foam cushion supports under the occiput can minimize decubitus, pressure- induced headache, palsies, and causalgia. Intraoperative traction on muscles and nerves should be started carefully and monitored during the operation to prevent reflex myalgias and causalgias. Painful swallowing after head and neck; ear, nose, and throat; and endocrine surgical procedures may require elixir (i.e., liquid) forms of pain medicine, a modified diet, including liquid or soft foods, and occasional use of topical anesthetics such as viscous lidocaine.

Postoperative pain is often short term and of moderate intensity. Within 1-3 days, parenteral and oral opioids can be discontinued or replaced with non-opioid analgesics (which may have to be delivered via gastrostomy or jejunostomy). The use of most NSAIDs may be contraindicated for such procedures as thyroidectomy and parathyroidectomy where postoperative hemorrhage and risk of airway obstruction are significant. In such cases, acetaminophen or "platelet- sparing" NSAIDs may be ordered.


Patients undergoing an operation on the central nervous system frequently show abnormal neurologic signs and symptoms that must be closely followed in the postoperative period. In addition, these patients may receive drugs designed to reduce cerebral edema or prevent seizures. A major dilemma in this clinical setting is the need to carefully monitor critical neurologic signs such as pupillary reflexes and the level of consciousness that may be affected by conventional opioid analgesics used for the relief of postoperative pain.

Ideally, postoperative pain control should not interfere with the ability to assess a patient's neurologic status, particularly the level of consciousness, or with assessment of motor and sensory function following spinal cord surgery. Therefore, the administration of opioids, benzodiazepines, and anxiolytics, in particular, is relatively contraindicated. However, the clinician must balance the need for analgesia with the requirement for appropriate neurologic monitoring.

The uncomplicated postcraniotomy patient typically has mild to moderate pain and is readily managed by a short period of parenteral medications followed by oral analgesics. Laminectomy and other spinal procedures usually are more painful than craniotomies. Ketorolac, a parenteral NSAID, may be considered in this setting because it has no effect on the level of consciousness or pupillary reflexes. As mentioned previously, the use of nonsteroidal analgesics may be contraindicated in some postoperative settings when the risk of coagulopathy or hemorrhage is high, the need to assess fever is important, or when the degree of pain is higher than the analgesic ceiling of the agent. Epidural opioids and/or local anesthetics can minimize the need for systemic opioids and allow more accurate monitoring of brainstem and cerebral function.

However, a single dose of epidural morphine may produce significant blood concentrations  that in turn cause effects within the central nervous system. A recent study could not demonstrate a difference in neuropsychiatric functioning between patients receiving oral and epidural morphine. Furthermore, motor and sensory dysfunction associated with epidural local anesthetics (which are often coadministered with opioids) may obscure important neurologic signs. Again, remember to balance the need for adequate analgesia while minimizing the confounding central nervous system effects of analgesics and anesthetics.



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McCaffery M. (1979). Nursing Management of the Client with Pain, 2nd ed. Philadelphia: Lippincott.

Physicians' Desk Reference


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