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David Geffen School of Medicine

The Greatest Evil

Since man first walked upright, we have struggled to understand and conquer chronic pain.

By Mona Gable

MedMag Fall 10-Chronic PainTOM SPEAR HAS BEEN IN PAIN FOR 36 YEARS. He was 22 when he was riding along the freeway on his motorcycle, and a driver pulled off on the shoulder and suddenly cranked a U-turn in front of him. He slammed into the car, flew over and skidded 300 feet. When he came to rest, he had a severe compression fracture in his spine. He was hospitalized for 10 months.

Spear is 58 now. He has been married for 30 years, has four children and a successful real-estate business in Culver City, and he still hurts. He’s been on the narcotic patch fentanyl and taken the highest doses of oxycontin he could tolerate. There have been more operations than he can count, including what he calls the “big one” at UCLA, in 1998, when doctors ground up part of his hip and used the meal to fuse a vertebra in his lower back to one in his sacrum. He’d heard so many horror stories about failed back surgeries that he fought having one for two years. “It scared the bejesus out of me,” he says.

The operation did help. After six months of physical therapy, he was able to work again. And despite having a degenerative bone disease that causes the spine to buckle and squeeze the nerves like toothpaste from a tube, in many ways Spear feels blessed. His wife, Cyndee, has been a rock. She is a nurse, and “takes on the brunt of the worry about my health,” he says.

“The greatest evil is physical pain,” wrote Saint Augustine, and one of its many associated ills is that it afflicts the entire family. Between the pain and the opiates Spear was taking to blunt the vice gripping his spine, he wasn’t exactly easy to live with. The painkillers made him sharp, angry. He couldn’t do things with his kids. “I missed a significant portion of their lives,” he says.

But he couldn’t have functioned without the drugs. He also couldn’t have functioned without a caring physician to help him along the way. For Spear, that physician is F. Michael Ferrante, M.D., director of the UCLA Pain Management Center. “In my experience,” Spear says, “the difference between doctors and healers is healers have an intrinsic gift. I believe Dr. Ferrante has that.”

And, in fact, healers do make a profound difference. One study found that the most critical treatment factor affecting outcome was “the intensive involvement of a single physician.”

ONE OF THE CRUEL PARADOXES OF CHRONIC PAIN, whether it is from injury or an illness such as cancer, is that you can’t see it. It’s subjective, a complex perception involving sensation, cognition and emotion, a malady that afflicts some 50-million Americans. Unlike acute pain, which serves to warn you if you bang your toe to stop what you’re doing and pay attention to the injury, chronic pain is useless. It is a signaling in the central nervous system and the brain that’s gone awry, where the nerves keep screaming that the body hurts even after the original assault is healed.

In irritable bowel syndrome (IBS), for instance, one of the most common chronic-pain conditions in adolescents and children, the sensory signaling is heightened so much that eating hurts. “Children will be brought sometimes from one gastroenterologist to another, and despite all the usual tests looking for disease, everything looks normal,” says Lonnie Zeltzer, M.D., director of the Pediatric Pain Program at Mattel Children’s Hospital UCLA, and the author of a book for parents on chronic pain. “Often people go from doctor to doctor, or they’re sent to a psychologist. They can often feel, ‘The doctor thinks I’m crazy,’ without recognizing that pain signaling can take place in the brain.”

Why some people are able to endure chronic pain while others cannot is a mystery. But it is believed one’s experience with pain is an interplay of genetics, the intensity of the original acute pain and cultural and psychological differences. “It can affect you on a purely somatic basis. Many people are hopeless. There have been studies to suggest that people who have spirituality have a tendency to do better,” Dr. Ferrante says.

“We know that all pain is real,” says Dr. Zeltzer. “There are chemicals in the brain and central nervous system involved, and there are many ways that emotions and experience influence chronic pain.”

And because it is subjective, pain is troubling for many doctors. “I don’t think the medical community understands the complexity of pain patients,” says Dr. Ferrante.

This is especially true in the case of children and adolescents. In a recent article in Science Daily, pediatricians reported that the dearth of options available for managing children’s pain is one of the most difficult aspects of providing care. At the UCLA Pediatric Pain Program, Dr. Zeltzer and her colleagues are working to change that reality. “We think about chronic pain in children from a family perspective, from a developmental and a biopsychosocial one,” she says.

Founded in 1991, the program takes an interdisciplinary approach to chronic pain. Dr. Zeltzer’s team includes clinicians and researchers from traditional fields like psychology and psychiatry, but also alternative complementary therapies such as yoga, acupuncture, hypnotherapy, biofeedback, art and music therapy and massage.

Subhadra Evans, Ph.D., wants to see if, like accupuncture, yoga has demonstrated benefits for pediatric patients. She’s currently conducting two studies to determine yoga’s usefulness in reducing pain. She ultimately hopes to discover: “Is this a feasible, safe and efficacious approach for young people?”

MedMag Fall 10-Chronic Pain CardIn one study, 80 patients from ages 16 to 35 with rheumatoid arthritis are taking Iyengar yoga classes for six weeks. In a second study, young people ages 14 to 26 with IBS are practicing yoga for six weeks. Before each class, the IBS patients are doing a series of stress tests and having their heart rate and blood pressure and other measures taken. At the end of the six weeks, Dr. Evans will determine if the yoga improved symptoms.

ON A COOL MORNING IN MARCH, Spear is at a crossroads. Six years ago, his pain levels were soaring, and Dr. Ferrante implanted a neural stimulator, a small box similar to a pacemaker, in his hip. Tiny wires from the box delivered electrical impulses to his spinal cord. The idea behind the device is to confuse the pain signal and replace the pain with a sensation that is more benign.

For a time it worked beautifully. It also allowed Spear to cut back on the drugs that were making him edgy and dull. Then two years ago, for no apparent reason, the pain roared back to life. It was so severe, he lay in bed curled up in a ball. They finally wrestled it down after he spent two weeks in the hospital.

Now, Spear is considering having Dr. Ferrante implant a pain pump in his abdomen, a way to deliver opiates directly to the spine. As a consequence of the drugs he’s had to take, Spear can’t remember things, a side effect called “clouding.” If he saw a TV show and his wife plays it again a week later, it’s as if he’s never seen it. He forgot his anniversary. He hates not being able to remember. The pump could alleviate that.

Still, as with any surgery, there are risks. And in the realm of chronic pain, perhaps the biggest risk is that it might not work.

ALBERT SCHWEITZER CALLED PAIN “the most terrible of all the lords of mankind.” Two-thousand years before Christ, people were using opium to treat pain. But the history of pain research and modern pain treatment really begins in the 1800s. And much of that research story is told in the Louise M. Darling Biomedical Library at UCLA.

It is here that archivist Russell Johnson and historian Marcia Meldrum, Ph.D., oversee the John C. Liebeskind History of Pain Collection. In the 19th century, people accepted pain as a fact of life, Dr. Meldrum says, and most looked to religion to help them cope. Pain was even considered virtuous. “This was something God gave you to test your character,” she says, speaking in the library’s Rare Books Room against the backdrop of a poster from the 1930s depicting a man with a big grin and nails sticking out of his cheeks and chin.

Far from discouraging this concept of righteous pain, many physicians reinforced it. As for pain treatments, they often contained opium or morphine in an alcohol base and were sold over-the-counter. Even children and infants were given the drugs. For a teething baby, there was Mrs. Winslow’s Soothing Syrup, just such a blend of alcohol and morphine. “Many people used these to self-medicate,” Dr. Meldrum says.

When surgical anesthesia came along, in 1946, the belief that pain was somehow good for you began to fade. Yet, throughout the 19th century, many physicians resisted its use. “There were a lot of arguments about whether it was ethical,” says Dr. Meldrum. “‘The patient is completely unconscious, and you’re cutting him with knives?’”

The next revolution in pain treatment came in 1855, when physicians invented the hypodermic needle. It allowed doctors to easily administer morphine, and during the Civil War, it was liberally used to treat wounded soldiers. But when thousands of soldiers, and later civilians, developed addictions, doctors were faced with a conflict: Should they ease severe pain at the risk of addiction?

There was no such conflict over the “wonder drug” aspirin. Developed by a German chemist in 1897, Bayer aspirin soon became the best-selling analgesic in the world. “Try to imagine a world in which there wasn’t a good treatment for arthritis,” says Dr. Meldrum. “Aspirin was good for arthritis. It was good for toothaches. It was good for headaches.”

MedMag Fall 10-Chronic Pain Card3At the time, pain was understood to be a simple neural response to a single, unpleasant stimulus. Yet many sufferers of chronic pain didn’t fit this mold, so pain was stigmatized – the idea that it’s “all in your head.” “Most physicians didn’t understand pain and couldn’t treat chronic pain,” says Dr. Meldrum. “They thought the patient was a hypochondriac.”

William Livingston, M.D., didn’t share that view. From his work on athletes with sports injuries, the Oregon surgeon saw that chronic pain wasn’t just confined to tissue damage but was far more complex. During World War II, he and a handful of others pioneered using lidocaine blocks to treat soldiers with peripheral nerve injuries and other chronic problems. But for some, the relief was only temporary.

In 1946, Harvard anesthesiologist Henry Beecher, M.D., reported an astonishing discovery. In Italy during the war, he had observed that severely wounded soldiers reported far less pain than his surgery patients at Massachusetts General Hospital. The soldiers saw pain as a blessing because it meant they were leaving the war. “Contrast that with the patient who was yanked out of the comfort of home, operated on and was scared stiff,” says Dr. Meldrum. “He immediately started experiencing disabling pain.”

Dr. Beecher dubbed this response “the reaction component” – the idea that pain is individual and shaped by experience.

But one of the biggest advances in the pain field came in 1965. That year, Patrick Wall, D.M., and Ronald Melzack, Ph.D., published their legendary article in Science on the “gate theory,” completely changing how pain transmission was understood. Let’s say you stub your toe. If the “gate” in the spinal cord is open, the signals will be transmitted to the brain. If the gate is closed, they won’t. Unless the pain is strong enough, the gate will stay closed. But if you focus on the pain in your toe, you can force the gate open – in other words, thinking about pain can make pain worse. At the same time, recent studies have also shown that distracting yourself from pain can make it better. Although the gating mechanism described by Wall and Melzack was later refuted, their idea that simple pain stimuli are modified within the body laid the foundation for a whole new field of research.

“We now know at lot more about how thinking, ideas, memories and a sense of lack of control can neurologically increase metabolic activity in the pain centers of the brain,” says Dr. Zeltzer.

Melzack’s studies with young dogs also helped to show that pain is learned from a very young age. “This is one of the sad things about kids with pain,” says Dr. Meldrum. “It’s a learned response. But you can also learn how to manage it.”

It is a problem the UCLA Pediatric Pain Program is intently focused on. In a recent study of 244 families funded by the National Institutes of Health, Dr. Zeltzer and her colleagues explored how healthy kids respond to pain. The children and adolescents, who ranged from 8 to 17, were given a set of standardized laboratory pain tests, while their parents filled out questionnaires. The researchers looked at three things: gender differences in pain responses, differences between boys and girls based on pubertal development and early versus late puberty. Did children respond to pain differently as they went through puberty?

The results were striking. Girls were less tolerant of pain than boys, but this difference was only apparent among adolescents. Yet as boys got older, they became more tolerant of pain. It’s not clear why, but “it suggests that when children are younger, boys and girls should be treated more similarly in terms of pain,” says Jennie Tsao, Ph.D., research director for the UCLA Pediatric Pain Program. “But as children get older, boys may try to downplay or underreport their pain.”

Dr. Tsao and her colleagues also found a strong link between parents’ anxiety and an increased sensitivity to pain in girls, but not in boys. “Parents have a huge influence in terms of how their children respond to pain,” says Dr. Tsao. “We can’t modify parents’ genetics, but maybe we can help them manage their anxiety or how they role model in dealing with their pain and stress, in the hope that it helps their children.”

THE GATE MODEL TRIGGERED A RENAISSANCE in pain research, including several path-breaking studies at UCLA. In 1971, psychologist John Liebeskind, Ph.D., and his colleagues at UCLA made a stunning discovery: A certain area of the brain known as the periacqueductal gray produced an analgesic effect similar to opiate-like substances when an animal was stressed. What if sufferers of chronic pain could tap into that effect? This soon led to a surge of interest in alternative treatments to help patients manage pain.

Dr. Liebeskind also made another profound discovery: Chronic pain was far more destructive than physicians knew. “Before, we didn’t think there were consequences on the nervous system,” says psychiatrist and pain specialist Thomas Strouse, M.D., medical director of the Stewart and Lynda Resnick Neuropsychiatric Hospital at UCLA. “Dr. Liebeskind showed that chronic pain causes pathologic changes to the nervous system. It was he who coined the phrase ‘pain kills.’”

Dr. Liebeskind died of cancer in 1997. But his work lives on in the oral histories he recorded of his colleagues, and in his students. “He was very instrumental in producing the next generation of researchers,” says Dr. Meldrum.

The ’90s were a watershed in the pain movement. After persistent advocacy by regional, national and international pain societies, pain was made the fifth vital sign in healthcare, as critical to understanding a patient’s health as heart rate or blood pressure.

That decade also brought an increased acceptance by doctors of the value of opioids in treating pain – a dramatic shift from the ’70s and ’80s. “In the culture of medical training,” says Dr. Strouse, “most of us were trained that opioids are bad, and people who need them are bad, so we should not reinforce that by treating with opioids.”

But the ’90s also brought a wave of prescription-drug abuse. As a result, doctors and patients had new fears about addiction, many of them uninformed.

As Dr. Strouse emphasizes, there’s a big difference between addiction and dependence. “Any patient with chronic pain who takes opiates regularly for more than a few weeks is going to develop physiologic dependence, an entirely normal and predictable phenomenon. The cardinal symptom of dependence is evidence of withdrawal if the medicine is abruptly stopped. This is avoided by stepwise dose reduction. Addiction,” he says, “is a pathologic state. It includes loss of control over one’s use behavior and continued use of the drug despite negative consequences. No one would say it’s a good outcome.”

MedMag Fall 10-Pain DestroyerIf pain specialists have learned anything over the past 25 years, it is this: Not all pain is equal. Pain associated with tissue injury, or “nociceptive” pain, can come from soft tissues, bone, nerve, hollow viscera and other sources. Optimal pain management and drug selection takes these variables into consideration. “It is important for doctors to evaluate the kind of pain they’re observing,” says Dr. Strouse, “and to articulate what the issue is, and what does the clinical science and his or her clinical experience say is going to be the best treatment?”

SPEAR DID HAVE THE PAIN PUMP PUT IN. It rests in his abdomen, and a line carries morphine to a catheter in his spinal cord. “It’s been tremendous,” he says. “It removed that whole level of pain in my system that would spin out of control.”

In early September, he’d just returned from a trip to Alaska, where he hiked and flew in a helicopter. His memory is better, his mind clearer. “I feel much more human,” he says.

He’s still wearing a pain patch but has been able to reduce his oral medication by about 25 percent. Eventually, he wants to wean himself off those drugs entirely. “I have every reason to believe I’ll accomplish my goal,” he says.

Asked to reflect on his long journey, Spear offers a hopeful message: “You need to get with the right caregivers,” he says. “Then you have to take responsibility for your health. I think you have to never give up. There’s always something that can be done better.”

Mona Gable is a freelance writer in Los Angeles.


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