Chronic pain is different. Chronic pain persists. Fiendishly, uselessly, pain signals keep firing in the nervous system for weeks, months, even years. There may have been an initial mishap-a sprained back, a serious infection-from which you've long since recovered. There may be an ongoing cause of pain-arthritis, cancer, ear infection. But some people suffer chronic pain in the absence of any past injury or evidence of body damage. Whatever the cause, chronic pain is real, unremitting, and demoralizing-the kind of pain New England poet Emily Dickinson had in mind when she wrote:

Pain of such proportions overwhelms all other symptoms and becomes the problem. People so afflicted often cannot work. Their appetite falls off. Physical activity of any kind is exhausting and may aggravate the pain. Soon the person becomes the victim of a vicious circle in which total preoccupation with pain leads to irritability and depression. The sufferer can't sleep at night and the next day's weariness compounds the problem-leading to more irritability, depression, and pain. Specialists call that unhappy state the "terrible triad" of suffering, sleeplessness, and sadness, a calamity that is as hard on the family as it is on the victim. The urge to do something-anything-to stop the pain makes some patients drug dependent and drives others to undergo repeated operations or resort to questionable practitioners who promise quick and permanent "cures."

Many chronic pain conditions affect older adults. Arthritis, cancer, angina-the chest-binding, breath-catching spasms of pain associated with coronary artery disease-commonly take their greatest toll among the middle-aged and elderly. Trigeminal neuralgia (tic douloureux) is a recurrent, stabbing facial pain that is rare among young adults. But ask anyone living in a community for retired persons if there are any trigeminal neuralgia sufferers around and you are sure to hear of cases. So the fact that Americans are living longer contributes to a widespread and growing concern about pain.

Neuroscientists share that concern. At a time when people are living longer and painful conditions abound, the scientists who study the brain have made landmark discoveries that are leading to a better understanding of pain and more effective treatments.

In the forefront of pain research are scientists supported by the National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health (NIH). Other institutes at NIH that support pain research include the National Institute of Dental Research (NIDR), the National Cancer Institute (NCI), the National Institute of Nursing Research (NINR), the National Institute on Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH).

In the past several decades, important discoveries about pain-suppressing chemicals came about because scientists were curious about how morphine and other opium-derived painkillers, or analgesics, work. For some time neuroscientists had known that chemicals were important in conducting nerve signals (small bursts of electric current) from cell to cell. In order for the signal from one cell to reach the next in line, the first cell secretes a chemical, called a "neurotransmitter," from the tip of a long fiber that extends from the cell body. The transmitter molecules cross the gap separating the two cells and attach to special receptor sites on the neighboring cell surface. Some neurotransmitters excite the second cell-allowing it to generate an electrical signal. Others inhibit the second cell-preventing it from generating a signal.

When investigators injected morphine into experimental animals, they found that the morphine molecules fit snugly into receptors on certain brain and spinal cord neurons. Why, the scientists wondered, should the human brain-the product of millions of years of evolution-come equipped with receptors for a man-made drug? Perhaps there were naturally occurring brain chemicals that behaved exactly like morphine.

Numerous studies around the world led to the discovery of not just one pain-suppressing chemical in the brain, but a whole family of such proteins. The smaller members of the family were named enkephalins (meaning "in the head"). In time, the larger proteins were isolated and called endorphins, meaning the "morphine within." The term endorphins is now often used to describe the group as a whole.

The discovery of the endorphins lent weight to an overarching theory of pain: endorphins released from brain nerve cells might inhibit spinal cord pain cells through pathways descending from the brain to the spinal cord. Laboratory experiments subsequently confirmed that painful stimulation led to the release of endorphins from nerve cells. Some of these chemicals then turned up in cerebrospinal fluid, the liquid that circulates in the spinal cord and brain. Laced with endorphins, the fluid could bring a soothing balm to quiet nerve cells.

Further evidence that endorphins figure importantly in pain control came from studies of some of the oldest and newest pain treatments. These studies involved the use of a drug called naloxone that prevents endorphins and morphine from working. Injections of naloxone resulted in a return of pain which had been relieved by morphine and certain other treatments. But, interestingly, some pain treatments are not affected by naloxone: their success in controlling pain apparently does not depend on endorphins. Thus nature has provided us with more than one means of achieving pain relief.

Those same investigators note that naloxone injections can block pain relief produced by acupuncture. Others have not been able to repeat those findings. Skeptics also cite long-term studies of chronic pain patients that showed no lasting benefit from acupuncture treatments. Current opinion is that more controlled trials are needed to define which pain conditions might be helped by acupuncture and which patients are most likely to benefit.

Local electrical stimulation. Applying brief pulses of electricity to nerve endings under the skin, a procedure called transcutaneous electrical nerve stimulation (TENS), yields excellent pain relief in some chronic pain patients. The stimulation works best when applied to the skin near where the pain is felt and where other sensibilities like touch or pressure have not been damaged. Both the frequency and voltage of the electrical stimulation are important in obtaining pain relief.

Brain stimulation. Another electrical method for controlling pain, especially the widespread and severe pain of advanced cancer, is through surgically implanted electrodes in the brain. The patient determines when and how much stimulation is needed by operating an external transmitter that beams electronic signals to a receiver under the skin that is connected to the electrodes. Stimulation-produced analgesia is a costly procedure that involves the risk of brain surgery. However, patients who have used this technique report that their pain "seems to melt away." The pain relief is also remarkably specific: the other senses remain intact, and there is no mental confusion or cloudiness as with opiate drugs.

Placebo effects. For years doctors have known that a harmless sugar pill or an injection of salt water can make many patients feel better-even after major surgery. The placebo effect, as it is called, has been thought to be due to suggestion, distraction, the patient's optimism that something is being done, or the desire to please the doctor (placebo means "I will please" in Latin).

Later experiments suggested that the placebo effect may be neurochemical, and that people who respond to a placebo for pain relief-a remarkably consistent 35 percent in any experiment using placebos-are able to tap into their brains' endorphin systems. To evaluate it, investigators designed an ingenious experiment. They asked adults scheduled for wisdom teeth removal to volunteer in a pain experiment. Following surgery, some patients were given morphine, some naloxone, and some a placebo. As expected, about a third of those given the placebo reported pain relief. The investigators then gave these people naloxone. All reported a return of pain.

How people who benefit from placebos gain access to pain control systems in the brain is not known. Scientists cannot even predict whether someone who responds to a placebo in one situation will respond in another. Some investigators suspect that stress may be a factor. Patients who are very anxious or under stress are more likely to react to a placebo for pain than those who are more calm, cool, and collected. But dental surgery itself may be sufficiently stressful to trigger the release of endorphins-with or without the effects of placebo. For that reason, many specialists believe further studies are indicated to analyze the placebo effect.

As research continues to reveal the role of endorphins in the brain, neuroscientists have been able to draw more detailed brain maps of the areas and pathways important in pain perception and control and have found other members of the endorphin family. At the same time, clinical investigators have tested chronic pain patients and found that they often have lower-than-normal levels of endorphins in their spinal fluid. If we could just boost their stores with man-made endorphins, perhaps the problems of chronic pain patients could be solved.

Not so easy. Some endorphins are quickly broken down after release from nerve cells. Other endorphins are longer lasting, but there are problems in manufacturing the compounds in quantity and getting them into the right places in the brain or spinal cord. In a few promising studies, clinical investigators have injected an endorphin called beta-endorphin under the membranes surrounding the spinal cord. Patients reported excellent pain relief lasting for many hours. Morphine compounds injected in the same area are similarly effective in producing long-lasting pain relief.

But spinal cord injections or other techniques designed to raise the level of endorphins circulating in the brain require surgery and hospitalization. And even if less drastic means of getting endorphins into the nervous system could be found, they are probably not the ideal answer to chronic pain. Endorphins are also involved in other nervous system activities such as controlling blood flow. Increasing the amount of endorphins might have undesirable effects on these other body activities. Endorphins also appear to share with morphine a potential for addiction or tolerance.

Meanwhile, chemists are synthesizing new analgesics and discovering painkilling virtues in drugs not normally prescribed for pain. Much of the drug research is aimed at developing nonnarcotic painkillers. The motivation for the research is not only to avoid introducing potentially addictive drugs on the market, but is based on the observation that narcotic drugs are simply not effective in treating a variety of chronic pain conditions. Developments in nondrug treatments are also progressing, ranging from new surgical techniques to therapies like exercise, hypnosis, and biofeedback.

When you complain of headache or low back pain and the doctor says take two aspirins every 4 hours and stay in bed, you may think your pain is being dismissed lightly. Not at all. Aspirin, one of the most universally used medications is an excellent painkiller. Scientists still cannot explain all the ways aspirin works, but they do know that it interferes with pain signals where they usually originate, at the nerve endings outside the brain and spinal cord: peripheral nerves. Aspirin also inhibits the production of chemicals called prostaglandins that are manufactured in the blood to promote blood clotting and wound healing. Unfortunately, prostaglandins, released from cells at the site of injury, are pain-causing substances. They actually sensitize nerve endings, making them-and you-feel more pain. Along with increasing the blood supply to the area, these chemicals contribute to inflammation-the pain, heat, redness, and swelling of tissue damage.

Some investigators now think that the continued release of pain-causing substances in chronic pain conditions may lead to long-term nervous system changes in some patients, making them hypersensitive to pain. People suffering such hyperalgesia can cry out in pain at the gentlest touch, or even when a soft breeze blows over the affected area. In addition to the prostaglandins, blister fluid and certain insect and snake venoms also contain pain-causing substances. Presumably these chemicals alert you to the need for care-a fine reaction in an emergency, but not in chronic pain.

There are several prescription drugs that usually can provide stronger pain relief than aspirin. These include the opiate-related compounds codeine, propoxyphene, morphine, and meperidine. All these drugs have some potential for abuse, and may have unpleasant and even harmful side effects. In combination with other medications or alcohol, some can be dangerous. Used wisely, however, they are important recruits in the chemical fight against pain.

In the search for effective analgesics, physicians have discovered pain-relieving benefits from drugs not normally prescribed for pain. Certain antidepressants are used to treat several particularly severe pain conditions, notably the riveting pain of facial neuralgias like trigeminal neuralgia and the excruciating pain that can follow an attack of shingles.

Interestingly, pain patients who benefit from antidepressants report pain relief before any uplift in mood. Pain specialists think that the antidepressant works because it increases the supply of a naturally produced neurotransmitter, serotonin. (Doctors have long associated decreased amounts of serotonin with severe depression.) But now scientists have evidence that cells using serotonin are also an integral part of a pain-controlling pathway that starts with endorphin-rich nerve cells high up in the brain and ends with inhibition of pain-conducting nerve cells lower in the brain or spinal cord.

Antiepileptic drugs have also been used successfully in treating trigeminal neuralgia. The rationale for the use of antiepileptic drugs (principally carbamazepine) is based on the theory that a healthy nervous system depends on a proper balance of incoming and outgoing nerve signals. Trigeminal neuralgia and other facial pains or neuralgias are thought to result from damage to facial nerves. That means that the normal flow of messages to and from the brain is disturbed. The nervous system may react by becoming hypersensitive: it may create its own powerful discharge of nerve signals, as though screaming to the outside world "Why aren't you contacting me?" Antiepileptic drugs-used to quiet the excessive brain discharges associated with epileptic seizures-quiet the distress signals and in that way may relieve pain.

Treatment for pain can include counseling, relaxation training, meditation, hypnosis, biofeedback, or behavior modification. The philosophy common to all of these approaches is the belief that patients can do something on their own to manage their pain. That something may mean changing attitudes, feelings, or behaviors associated with pain.

Psychotherapy. Some patients may benefit from individual or group counseling. Trained professionals can help the chronic pain sufferer learn valuable coping skills. They also provide the patient with much needed support-both psychological and emotional-for dealing with pain.

Relaxation and meditation therapies. These methods enable people to relax tense muscles, reduce anxiety, and alter mental states. Both physical and mental tension can make pain worse, and in conditions such as headache or back pain, tension may be at the root of the problem. Meditation, which aims at producing a state of relaxed but alert awareness, is sometimes combined with therapies that encourage people to think of pain as something remote and apart from them. The methods promote a sense of detachment so that the patient thinks of the pain as confined to a particular body part over which he or she has control. The approach may be particularly helpful when pain is associated with fear, as in cancer.

Hypnosis. No longer considered magic, hypnosis is a technique in which an individual's susceptibility to suggestion is heightened. Normal volunteers who prove to be excellent subjects for hypnosis often report a marked reduction or obliteration of experimentally induced pain, such as that produced by a mild electric shock. The hypnotic state does not lower the volunteer's heart rate, respiration, or other autonomic responses. These physical reactions show the expected increases normally associated with painful stimulation.

The role of hypnosis in treating chronic pain patients is uncertain. Some studies have shown that 15 to 20 percent of hypnotizable patients with moderate to severe pain can achieve total relief with hypnosis. Other studies report that hypnosis reduces anxiety and depression. By lowering the burden of emotional suffering, pain may become more bearable.

Biofeedback. Some individuals can learn voluntary control over certain body activities if they are provided with information about how the system is working-how fast their heart is beating, how tense their head or neck muscles are, how cold their hands are. The information is usually supplied through visual or auditory cues that code the body activity in some obvious way-a louder sound meaning an increase in muscle tension, for example. How people use this biofeedback to learn control is not understood, but some practitioners of the art report that imagery helps: they may think of a warm tropical beach, for example, when they want to raise the temperature of their hands. Biofeedback may be a logical approach in pain conditions that involve tense muscles, like tension headache or low back pain. But results are mixed.

Behavior modification. This psychological technique (sometimes called operant conditioning) is aimed at changing habits, behaviors, and attitudes that can develop in chronic pain patients. Some patients become dependent, anxious, and homebound-if not bedridden. For some, too, chronic pain may be a welcome friend, relieving them of the boredom of a dull job or the burden of family responsibilities. These psychological rewards-sometimes combined with financial gains from compensation payments or insurance-work against improvements in the patient's condition, and can encourage increased drug dependency, repeated surgery, and multiple doctor and clinic visits.

There is no question that the patient feels pain. The hope of behavior modification is that pain relief can be obtained from a program aimed at changing the individual's lifestyle. The program begins with a complete assessment of the painful condition and a thorough explanation of how the program works. It is essential to enlist the full cooperation of both the patient and family members. The treatment is aimed at reducing pain medication and increasing mobility and independence through a graduated program of exercise, diet, and other activities. The patient is rewarded for positive efforts with praise and attention. Rewards are withheld when the patient retreats into negative attitudes or demanding and dependent behavior.

How effective are any of these treatment methods? Are some superior to others? Who is most likely to benefit? Do the benefits last? The answers are not yet in hand. Patient selection and patient cooperation are all-important. Analysis of individuals who have improved dramatically with one or another of these approaches is helping to pinpoint what factors are likely to lead to successful treatment.

Surgery is often considered the court of last resort for pain: when all else fails, cut the nerve endings. Surgery can bring about instant, almost magical release from pain. But surgery may also destroy other sensations as well, or, inadvertently, become the source of new pain. Further, relief is not necessarily permanent. After 6 months or a year, pain may return.

For all those reasons, the decision for surgery must always involve a careful weighing of the patient's condition and the outlook for the future. If surgery can mean the difference between a pain-wracked existence ending in death, versus a pain-free time in which to compose one's life and see friends and family, then surgery is clearly a humane and compassionate choice.

There are a variety of operations to relieve pain. The most common is cordotomy: severing the nerve fibers on one or both sides of the spinal cord that travel the express routes to the brain. Cordotomy affects the sense of temperature as well as pain, since the fibers travel together in the express route.

Besides cordotomy, surgery within the brain or spinal cord to relieve pain includes severing connections at major junctions in pain pathways, such as at the places where pain fibers cross from one side of the cord to the other, or destroying parts of important relay stations in the brain like the thalamus, an egg-shaped cluster of nerve cells near the center of the brain. In addition, surgeons sometimes can relieve pain by destroying nerve fibers or their parent cell bodies outside the brain or spinal cord. A case in point is the destruction of sympathetic nerves (a part of the autonomic nervous system) to relieve the severe pain that sometimes follows a penetrating wound from a sharp instrument or bullet.

When pain affects the upper extremities, or is widespread, the surgeon has fewer options and surgery may not be as effective. Still, skilled neurosurgeons have achieved excellent results with upper spinal cord or brain surgery to treat severe intractable pain. These procedures may employ chemicals or use heat or freezing treatments to destroy tissue, as well as the more traditional use of the scalpel.

Some surgeons have reported success with a brain operation called cingulotomy to relieve intractable pain in patients with severe psychiatric problems. The nerve fibers destroyed are part of a pathway important in emotions and motivation. The surgery appears to eliminate the discomfort and suffering the patient feels, but does not interfere with other mental faculties such as thinking and memory.

Prior to operating, physicians can often test the effectiveness of surgery by using anesthetic drugs to block nerves temporarily. In some chronic pain conditions-like the pain from a penetrating wound-these temporary blocks can in themselves be beneficial, promoting repair of nerve damage.

How do these current treatments apply to the more common chronic pain conditions? What follows is a brief survey of major pain disorders and the treatments most in use today.

Headache. Tension headache, involving continued contractions of head and neck muscles, is one of the most common forms of headache. The other common variety is the vascular headache, involving changes in the pressure of blood vessels serving the head. Migraine headaches are of the vascular type, associated with throbbing pain on one side of the head. Genetic factors play a role in determining who will have migraines, but many other factors are important as well. A major difficulty in treating migraine headache is that changes occur throughout the course of the headache. Blood vessels may first constrict and then dilate. Changing levels of neurotransmitters have also been noted. While a number of drugs can relieve migraine pain, their usefulness often depends on when they are taken. Some are only effective if taken at the onset. Several drugs for the prevention of migraine have been developed in recent years, including serotonin agonists which mimic the action of this key brain chemical. Prompt administration of these drugs is important.

Drugs are also the most common treatment for tension headache, although attempts to use biofeedback to control muscle tension have had some success. Physical methods such as heat or cold applications often provide additional, if only temporary, relief.

Low back pain. The combination of pain-killers and modest amounts of a muscle relaxant are usually prescribed for the first-time low back pain patient. At the initial examination, the physician will also note if the patient is overweight or works under conditions (such as driving a truck or sitting at a desk for long hours) that offer little opportunity for exercise. Some authorities believe that low back pain is particularly prevalent in Western society because of the combination of overweight, bad posture (made worse if there is added weight up front), and infrequent exercise.

Although bed rest may be necessary for severe back problems, exercise is now considered to be an important addition to treatment and can help speed recovery for many patients with low back pain. Exercise helps reduce stress on the lower back by increasing flexibility and strength. To avoid injury, however, carefully follow the exercise routine prescribed by your doctor. In some cases, a full neurological examination may be necessary, including tests to determine if there may be a ruptured disc or other source of pressure on the cord or nerve roots.

Sometimes x-rays will show a disc problem that can be helped by surgery. Milder analgesics (aspirin, acetaminophen, or stronger nonnarcotic medications) and electrical stimulation-using TENS or implanted brain electrodes-can be very effective for low back pain. What is not effective is long-term use of muscle-relaxant tranquilizers. Many specialists are convinced that chronic use of these drugs is detrimental to the back pain patient, adding to depression and increasing pain. Massage and manipulative therapy are used by some clinicians but, except for individual patient reports, their usefulness is still undocumented.

Cancer pain. The pain of cancer can result from the pressure of a growing tumor or the infiltration of tumor cells into other organs. Or the pain can come about as the result of radiation or chemotherapy. These treatments can cause fluid accumulation and swelling (edema), irritate or destroy healthy tissue causing pain and inflammation, and possibly sensitize nerve endings. Ideally, the treatment for cancer pain is to remove the cancerous tissue. When that is not possible, pain can be treated by any or all of the currently available therapies: electrical stimulation, psychological methods, surgery, and strong painkillers.

Arthritis pain. Arthritis is a general descriptive term meaning a disorder of the joints. The two most common forms are osteoarthritis that typically affects the fingers and may spread to important weight-bearing joints in the spine or hips, and rheumatoid arthritis, an inflammatory joint disease associated with swelling, congestion, and thickening of the soft tissue around joints. Current treatments for arthritis include aspirin, acetaminophen, and nonsteroidal anti-inflammatory drugs like indomethacin and ibuprofen. Steroid drugs-important anti-inflammatory agents modeled after the body's own chemicals produced in the adrenal glands-were introduced and hailed as lifesavers in the 1950's. But the long-term use of steroids has serious consequences, among them the lowering of resistance to infection, hemorrhaging, and facial puffiness-producing the so-called moonface.

TENS and acupuncture have been tried with mixed results. In cases where tissue has been destroyed, surgery to replace a diseased joint with an artificial part has been very successful. The total hip replacement operation is an example.

Arthritis is best treated early, say the experts. A modest program of drugs combined with exercise can do much to restore full function and forestall long-term degenerative changes. Exercise in warm water is especially good since the water is both relaxing and provides buoyancy that makes exercises easier to perform. Physical treatments with warm or cold compresses are helpful sources of temporary pain relief.

Neurogenic pain. The most difficult pains to treat are those that result from damage to the peripheral nerves or to the central nervous system itself. Mentioned earlier in this brochure as examples of extraordinarily searing pain were trigeminal neuralgia and shingles, along with several drugs that can help in these conditions. In addition, trigeminal neuralgia sufferers can benefit from surgery to destroy the nerve cells that supply pain-sensation fibers to the face. An advantage to using a treatment called "thermocoagulation"-which uses heat supplied by an electrical current to destroy nerve cells-is that pain fibers are more sensitive to the treatment resulting in less destruction of other sensations (such as touch and temperature).

Sometimes specialists treating trigeminal neuralgia find that certain blood vessels in the brain lie near the group of nerve cells supplying sensory fibers to the face, exerting pressure that causes pain. The surgical insertion of a small sponge between the blood vessels and the nerve cells can relieve the pressure and eliminate pain.

Among other notoriously painful neurogenic disorders is pain from an amputated or paralyzed limb-so called "phantom" pain-that affects a significant number of amputees and paraplegia patients. Various combinations of antidepressants and weak narcotics like propoxyphene are sometimes effective. Surgery, too, is occasionally successful. Many experts now think that the electrical stimulating techniques hold the greatest promise for relieving these pains.

Psychogenic pain. Some cases of pain are not due to past disease or injury, nor is there any detectable sign of damage inside or outside the nervous system. Such pain may benefit from any of the psychological pain therapies listed earlier. It is also possible that some new methods used to diagnose pain may be useful. One method gaining in popularity is thermography, which measures the temperature of surface tissue as a reflection of blood flow. A color-coded "thermogram" of a person with a headache or other painful condition often shows an altered blood supply to the painful area, appearing as a darker or lighter shade than the surrounding areas or the corresponding part on the other side of the body. Thus an abnormal thermogram in a patient who complains of pain in the absence of any other evidence may provide a valuable clue that can lead to a diagnosis and treatment.