(FORTUNE Magazine) – THE WINSOME schoolgirl at right below, Jennifer Darling, 17, of Mansfield, Massachusetts, suffers from one of the most terrifying and mysterious conditions challenging modern medicine. It goes by the formidable name of reflex sympathetic dystrophy syndrome, RSDS for short, and as is typical, it started innocently enough. Three years ago Jennifer sprained her right wrist in gym class. A burning pain persisted -- ''like a hot iron on your arm,'' as she describes it -- and soon spread to her other arm and her legs. Painkilling medicines have been of little use. But she does get some relief through battery-powered electrodes implanted in her back and right arm; a weak (5 amp. or less) current, which she regulates with the computerized device she is holding, helps counteract the pain. RSDS is still rare, but you're likely to hear more and more about it. One reason: the explosion of carpal tunnel syndrome wrist injuries among continual users of computer keyboards. Unfortunately, surgery to correct the syndrome can also bring about RSDS. Help is on the way, though. While RSDS remains their toughest challenge, pain researchers are reporting major advances on other fronts. In the process they are rethinking old, often dismissive notions of pain and building a brief for swifter, more aggressive attacks on it. For example, patients who undergo major surgery -- an amputation, say, or the removal of a cancerous lung -- often face the additional ordeal of severe pain that can last months or even years. But a few lucky folks can count on virtually complete elimination of postoperative pain. Borrowing a trick from dentists, anesthesiologists at some research hospitals now pretreat the pain, and lessen it over the long pull, by injecting morphine at the site of the surgery as well as into the spinal cord. Weaker drugs can do the same for more routine procedures like biopsies and Caesarean sections. Medicine is finally starting to deal with pain effectively, thanks to two developments: research that has revealed more about how pain works and freer use of more precisely targeted drugs. Many new pain treatments are spreading into general practice -- albeit slowly -- while others are as yet available only through pain clinics at the most advanced medical centers. These innovative approaches not only spare patients suffering but also help keep down the appalling cost of health care. Increasingly doctors recognize that timely and proper treatment of pain can lead to faster, more complete recovery and even save lives. By shortening hospital stays and allowing patients to return to work sooner, good pain management pays off. The rethinking of pain is so new that some health insurers have yet to grasp the point. Specialists complain that a blunderbuss approach to cost cutting has led Medicare and many big health insurers that follow its lead to refuse to pay extra for nontraditional pain control. If this practice spreads, researchers fear, it could set back progress in pain treatment by years and subject countless people to unnecessary agony. Both the number of people in pain and the cost of treating them conventionally are astronomical. According to the National Institutes of Health (NIH), at least 40 million Americans -- more than one in seven -- suffer from chronic, debilitating pain that keeps them from functioning fully, at a cost of untold billions in lost output, wages, and taxes. As the population of the industrialized world ages, the demand for pain treatment will increase sharply. More people will contract diseases -- diabetes and cancer, for example -- that are often accompanied by chronic pain. When the U.S. Public Health Service published its first guidelines for managing severe pain early in 1992, the agency was inundated with requests for 825,000 copies. UNTIL RECENTLY, understanding the nature and treatment of pain lagged far behind the rest of medicine. Traditionally many doctors have viewed pain simply as a secondary symptom that goes away once a disease is dealt with -- nothing more than the body's alarm bells warning of injury or infection. Medical professionals are just beginning to digest the fact that pain can be much more -- sometimes a major component of disease or even a disease in its own right. Unlike touch or taste, pain is not a simple sensation. It involves a complex congeries of senses, memories, attitudes, and emotions that affect how people perceive pain and how their bodies respond to it. Sorting all this out has < engaged multidisciplinary teams of investigators skilled in neuroscience, physiology, physical therapy, anesthesiology, psychology, biofeedback, and other specialties. In the 1960s a pioneering neurologist, J. J. Bonica of the University of Washington, set up the world's first comprehensive pain clinic at the university hospital. Researchers at the NIH led by neurologist Ronald Dubner, as well as teams at other major medical centers, soon picked up the thread. From their multipronged attack, a theoretical framework has emerged that explains many longstanding puzzles. What scientists are discovering now is enough to shock even the most benighted practitioner into changing his ways. Among their discoveries:

-- Pain suppresses the immune system and enhances the development of cancerous tumors. Says John C. Liebeskind, a UCLA neurologist who made this remarkable discovery in rats: ''This finding argues strongly against the popular misconception: 'Pain won't kill you.' ''

-- Chronic pain damages neurons -- nerve cells -- in the spinal cord and possibly in the brain itself, according to new, unpublished findings by NIH scientists. Those damaged neurons malfunction, so a sufferer from chronic pain feels each successive injury more sharply. Says Dubner of the NIH: ''You must eliminate pain as soon as possible so that those changes in the brain don't become permanent, creating a permanently exaggerated pain response.''

-- In some serious conditions pain becomes more than merely a warning. It can significantly worsen an ailment. If pain keeps a bedridden patient from turning over often enough, for instance, he's more likely to develop a blood clot. If she can't take a deep breath because of pain, she's more likely to get pneumonia. If his blood pressure is high because of pain, he's more likely to suffer a heart attack.

''Pain is now recognized as a dynamic process -- it doesn't stay the same,'' says Daniel B. Carr, who directs the pain center at Massachusetts General Hospital in Boston. ''Pain is not simply the phenomenon of suffering but one dimension of a whole host of very important, linked body responses.'' He adds that it's almost impossible for a person to have severe pain without having some kind of response in the heart, the blood vessels, and elsewhere. ''We now have a whole armamentarium of new tools,'' says Dubner, made possible by unraveling the mysteries of how pain originates and how the body handles it. The traditional idea of specific, dedicated pathways carrying the message ''It hurts'' from all over the body to the brain dates back to the 17th century, but research in the past few decades has shown that things aren't quite so simple (see diagram). The big conceptual shift in understanding came about in 1965 with the formulation of a new theory of pain by Ronald Melzack, an American psychologist, and Patrick D. Wall, a British physiologist, both then at MIT. The two scientists were seeking answers to questions that the specific-path theory cannot resolve. For example: Why does the location of pain sometimes differ from the site of the damage? Why does the intensity of pain change over time?

The authors called their hypothesis ''gate control'' to indicate that a neural mechanism -- a ''gate'' in the spinal cord -- serves as a way station for pain signals going to the brain and modifies those signals en route. Like a gate, the neural mechanism can open or close, fully or partially, depending on the type of signals transmitted. TWO MAJOR ADVANCES in the 1970s bolstered the gate-control theory. First, scientists discovered that an ascending system toward the brain does originate in the fine nerve endings in the skin -- at the fingertips, for example. Contrary to the specific-path theory, however, these sensors are not specialized pain receptors; they also respond to pressure, temperature, and touch. In reaction to such stimuli, an electrical signal flashes at 225 mph through the nerve fibers to the spinal cord, reporting what's going on at the site of injury. In the spinal cord scientists traced the incoming signals entering specialized neurons for transmission to the brain. Although an area known as the thalamus processes pain signals, the brain has no single pain control center. Instead the spinal cord gate relays signals from injured parts of the body to regions of the brain governing mood, movement, and perception, among other things. What you ultimately perceive as pain is the sum of all this processing, comparing, weighing, modulating, and amplifying of signals. The brain and the nervous system possess an adaptability no man-made computer can match. The nervous system's amazing ability to grow new extensions to existing circuits is what makes learning possible. But no one knew that such changes, along with subtle shifts in the chemical neurotransmitters that help the brain and nerves communicate, also take place in processing pain. That's why surgery seldom works against recurring pain. By the time pain becomes chronic, new networks are already in place. The second big discovery of the 1970s -- a major triumph of biology -- was the detection of descending pathways that modify pain signals as they make their way outward from the parts of the brain that govern cognition, motivation, and mood. Down some of these pathways the brain sends opiumlike painkillers called endorphins. In other pathways scientists detected different pain modulators, including serotonin and norepinephrine, a relative of adrenaline. Researchers also found that a welter of other chemicals are involved in pain regulation in the spinal cord; their roles are still being sorted out. The discovery of endorphins cleared up an ancient puzzle. How can a soldier in combat fail to notice a serious wound until the battle is over? How can a football player run for a touchdown on a broken ankle without feeling pain? Endorphins are the answer. They produce a temporary morphinelike painkilling effect by locking onto the same receptors -- docking ports -- on the surfaces of neurons that morphine also attaches to. This release of the body's own opiates evolved as a survival mechanism. You can see why. To escape a predator in the wild, man had to be able to run on a broken foot. But if he kept going for a long time without feeling pain, he would cripple himself. That's why endorphins shut off soon after an injury, so the injured person will start to feel pain and stop to allow tissue and bone to heal. UNFORTUNATELY scientific understanding of pain has leapfrogged the development of new painkillers. So physicians specializing in treatment of acute pain have resorted to using an old standby -- morphine -- in new ways. Unlike weaker, aspirin-based painkillers that suppress pain by blocking synthesis of harmful substances in arthritic joints, for example, morphine works both in the brain and in the spinal cord. In fact, doctors now deliver small doses of morphine directly into the spinal cord for faster relief without side effects. One big recent advance has been the recognition that morphine and other opioids -- opium derivatives -- almost never lead to addiction when used for pain-killing. In the streets extreme overuse of opioids can lead to addiction, though not invariably. However, all the studies and clinical observations show that addiction as a result of prolonged use of opioids as painkillers happens to fewer than one in a thousand patients. Even so, because use of narcotics even for medicinal purposes is severely restricted in some states and because doctors understandably fear getting in trouble with the law, cancer patients in severe pain frequently get less medication than they should. ''Most physicians don't know how to use these drugs properly,'' says Kathleen Foley, who directs the pain clinic at Memorial Sloan-Kettering Cancer Center in New York City. Patients themselves sometimes contribute to the undermedication. Having been brought up to think that withstanding pain is manly or noble, they sometimes fail to report pain to their doctors. Sloan- Kettering, Mass General, and other advanced pain treatment centers are trying to solve the communications problem by having the patient describe the pattern of pain he experiences and either displaying that information visually on a bedside card or making sure a nurse takes note of it when the doctor makes his rounds. Says Annabel Edwards, the nurse at the Mass General pain center: ''It doesn't matter how you keep track of the pain, as long as you do it consistently for each patient.'' If the arsenal of painkillers hasn't changed, however, methods for administering morphine and other opioids have. In recent years engineers have developed sophisticated devices like electronically controlled pumps that patients operate themselves. This approach, called patient-controlled analgesia, or PCA, allows the patient to give himself a dose of the drug without waiting for a busy nurse who may take an hour to show up. Patients use their own judgment about how much of the drug they need; the devices have safeguards to prevent overuse. A pump made by Bard MedSystems, a subsidiary of C.R. Bard Inc. of North Reading, Massachusetts, won't deliver a dose more often than every few minutes no matter how frequently a patient presses the release button. The experience at big pain clinics like Mass General's, which owns 120 Bard pumps, shows that most patients give themselves smaller overall doses than they would have got under the old every-four-hours system. Reason: The narcotics work best in smaller, more frequent doses. Says nurse Edwards: ''Most patients love the pumps.'' An array of other patient-controlled painkilling devices are already here or under development. Alza Corp. of Palo Alto, California, a pioneer in drug delivery, makes a patch with the opioid fentanyl that releases controlled , amounts of the drug through the skin for up to 72 hours. That allows cancer patients to sleep through the night. The patch is sold by Janssen Pharmaceutica, a subsidiary of Johnson & Johnson. Alza, Elan Corp. of Athalone, Ireland, and other companies are also working on slow-release patches and on devices that use an electrical current generated by a tiny battery to deliver medication on demand. Elan is also seeking FDA approval of a wristwatch-size system called Panoject for administering painkillers to ambulatory patients at the press of a button. Dozens of companies, including Abbott Laboratories, Medtronic, and Pharmacia Deltec Inc., make pumps, implantable systems, and similar devices to control pain more effectively. SADLY even morphine is often helpless against some particularly painful conditions. In those diseases the alarm seems to get stuck. The value of pain signals as a warning bell is easy enough to understand. Without them man would have a shorter life span -- those few unfortunate people born without sensitivity to pain usually do. At the other extreme, in people hypersensitive to pain, the alarm never shuts off. What could be the possible survival value of extreme chronic pain so severe that it can drive people to suicide? David Borsook, a neuroscientist at Mass General, calls it ''a kind of mistake in design'' of the nervous system. Treating chronic pain, including damage to the nerves, is the biggest challenge still facing the pain fighters. They are making some headway, owing partly to the new theoretical understanding of how pain works. What scientists needed was to be able to induce pain in lab animals, then trace and measure its progression. In 1988, NIH neurophysiologist Gary J. Bennett and Xie Yikuan, a visiting scientist from China, did just that when they tracked signals from an injured rat's paw to the spinal cord and the brain. Those findings cast light on how pain works in man and help explain why chronic and debilitating pain occurs when nerves in the hands, arms, legs, and elsewhere are damaged by injury or disease -- as often happens with such widespread ailments as diabetes and shingles. In RSDS cases like Jennifer Darling's, where the whole body can become inflamed with persistent pain after a seemingly innocuous injury, normally harmless stimuli such as a gentle touch, bright sunlight, even a loud noise, produce agony. Bennett and Xie's rat model suggests that the nonstop pain signals somehow bypass the usual modulating mechanisms, bombarding neurons in the spinal cord or the brain and deforming them so that they respond to nerve messages from larger and larger areas of skin. The nervous system misinterprets touch or heat signals, falsely announcing them as pain even after the original wound has healed. NIH scientists hope to find clues to RSDS by scanning the brains of sufferers. IN THIS and other types of chronic pain, doctors face a shortage of suitable drugs to experiment with. In the past, big pharmaceutical companies have preferred to concentrate on aspirinlike headache and arthritis painkillers, which are more profitable than complex drugs for chronic pain. (One exception: Glaxo, which has just introduced the highly effective antimigraine drug, Imitrex, that selectively constricts blood vessels in the brain.) Scrambling for drugs to work with, pain researchers have reached into other shelves of the medicine chest. Recently, for example, NIH neurologist Mitchell Max and his colleague Michael Byas-Smith succeeded in relieving chronic pain in about one-fourth of a small group of diabetics with clonindine, a drug normally used to control high blood pressure. Clonindine, made by Germany's Boehringer-Ingelheim, works on the same receptors as the neurotransmitter norepinephrine; those receptors are believed to be involved also in chronic pain. The scientists' guess has paid off for patients like Richard Feldman, 67, a semiretired Chicago salesman of industrial tools, and Clayton Larson, 71, of Traverse City, Michigan, a manager who retired from Snap-on Tools Corp. Before joining the NIH study about two years ago, the men, both diabetics suffering chronic pain, had made the rounds of physicians and hospitals with little result. ''The pain was driving me crazy,'' says Feldman. ''It was like having a toothache in your toes,'' says Larson. Clonindine helped both men. Feldman now wears a clonindine-releasing patch made by Alza, while Larson took the drug orally once a day for about a year and now uses it only occasionally. Neither Larson's nor Feldman's pain has completely disappeared, however. Larson says he is constantly reminded of it, but that on a scale of 1 to 10, it was once 7 to 9 but now rates 2 or 3. Where he once felt ''like I was walking on hot coals'' and tried to keep off his feet, he now stays busy restoring historic ships for the Great Lakes Maritime Heritage Association and volunteering at a hospice. Feldman puts in three days a week as a salesman. ''Nothing worked before,'' he says. ''Now, once in a while I get a little twinge, but the patch keeps it under control. It's a difference of 100%.'' The battle against chronic pain is still in its early stages. As Annabel Edwards of Mass General puts it: ''We can't guarantee that we can help everybody. But almost always we can at least make an improvement. In some people we can cure, or stop, the pain. But we don't expect to eliminate it totally in every case. We just do the best we can to bring it as low as we can.'' No cure, in other words, but at least -- as they say -- some relief.

BOX: HOW PAIN SIGNALS TRAVEL TO THE BRAIN

The electrochemical signals that make you say ''ouch' when you hurt your little finger originate in specialized nerve endings called nociceptors, from the Latin nocere (to harm). They occur in specialized nerve endings in your skin, muscles, and internal organs. Pain signals flash to the dorsal horn, a section of the spinal cord with nerve circuits that act as gates. (The dorsal horn runs the length of the spine.) The gates modulate the signals and pass them on to the amygdala, hypothalamus, thalamus, and cortex -- parts of the brain that deal with emotions and memory as well as pain. Through a descending pathway, the brain in turn controls the processing of pain signals in the spinal cord and releases the body's own painkillers, called endorphins. If pain signals damage neurons in the spinal cord or in the brain itself, pain may persist after its source has disappeared -- which explains why some amputees feel pain in an arm or leg removed years before. Local anesthetics, aspirin, and opium-based drugs like morphine act to stanch pain in different ways at different stages of the process.