Chronic Fatigue Syndrome (CFS) & Fibromyalgia (FM): The paradox of pain–a doctor’s search for why

(editor’s note: this is part one of a two part series describing one physician’s attempts to understand pain through 30 years of research.)

When pain pills and a heating pad couldn’t help mask the severe pains searing through her lower back, Sandra Coulter would climb into her bathtub. “I would sit in a hot tub for hours. It was the only way I could relieve the pain,” recalls Coulter. “It was excruciating.”

For three years, Coulter dealt with her debilitating torment until shortly after work one day, she fainted. Surgery eventually cured Coulter’s problem, but she is among tens of thousands of women–and as many men–who encounter the phenomenon of chronic pain–deep-seated hurting that seemingly lasts forever and that in many cases has no discernible cause.

But chronic pain is hardly a respecter of gender, says Dr. Karen Berkley (Ph.D. Washington) a neuroscientist who has made pain the focus of 30 years of research and teaching at FSU. Both men and women are subject to real, unrelenting pain that may or may not be traceable to organic disorders such as cancer, arthritis, gastrointestinal disease or to bodily injury.

In all her areas of research, Berkley, a McKenzie Professor in Florida State University’s Program in Neuroscience, is guided by the curious paradox of pain.

“Pain is always a motivator,” she said. “It’s extremely important–it alerts us that we need to take care of an injury that may have taken place. Without pain, we don’t survive very well.”

But constant, wracking pain also is a motivational force millions would like to live without. The National Institutes of Health estimates that up to 90 million Americans are chronic pain sufferers. In fact, chronic pain is the costliest health problem in the nation, totaling upwards of $100 billion annually in treatment costs, lost time from work, insurance pay-outs and legal bills.

Berkley is a member of a small international network of scientists who regard the phenomenon of chronic pain as one of the most challenging issues in the field of neurobiology, the science given over to the study of how the nervous system works. In the past 25 years, research into the cause and treatment of chronic pain has made extraordinary progress that has given hope to millions of sufferers worldwide.

Such strides include a host of therapies that range from the development of better and more economical pain-killing drugs to very expensive, high-tech treatments such as brain-implanted electrodes. Researchers have now found ways that the old stand-by morphine, for example, can be used safely and more often than ever before.

Some of the most exciting research surrounds the discovery of a class of pain-reducing proteins–called endorphins–produced by the body itself. These natural compounds come in a variety of strengths, researchers have found, and one of the latest discovered, called dynorphin, is reportedly 10 times more potent than morphine.

But despite the promise that both new and old treatments hold, for many victims of chronic pain nothing seems to work. Sufferers who have “tried it all” often are those whose conditions seem to defy all scientific and medical knowledge about the root causes of chronic pain and how to alleviate it. These unfortunates often make life hard for their families, and are ripe candidates for drug dependence, rip-offs from frauds selling miracle cures, despondency and depression. Often such sufferers are ultimately written off as “head cases,” a label that can be as socially debilitating as the condition itself.

Berkley says the mysterious nature of chronic pain–how it so obviously differs from the normal “ouch” variety–makes it one of the most interesting and important candidates for continued research. Unlike everyday scrapes, bumps and bruises that an aspirin can take care of, by its clinical definition chronic pain lasts at least six months and often has no obvious cause. But what clinicians and scientists call “acute” pain from traumatic injuries or common maladies can trigger chronic anguish long after an injury has healed or a painful disease has been cured.

Berkley’s research is focused on improving our understanding of how such unnecessary and often useless pain develops. This fall, she was in London finishing up a year-long sabbatical from FSU as a visiting professor at University College and at the National Hospital for Neurology and Neurosurgery. Her stay has afforded her opportunities to extend the medical applications of her research at FSU. Her sphere of research interests now includes colleagues working in Japan, Italy, Sweden and Canada, as well as in Britain, all of whom have visited her FSU lab at one time or another.

The Panoply of Pain

A consensus is emerging among Berkley’s group that researchers who study chronic pain need to begin rethink the way the body’s whole system of pain works. To Berkley and her colleagues, the often inexplicable manifestations and behavior of chronic pain suggest that the conventional theories of how the entire nervous system–the brain, spinal cord and all the peripheral nerves–create the perception of pain need to be changed.

Med schools generally teach that pain is a fairly straightforward response to injury. Abnormal amounts of pressure, heat and certain chemicals in injured tissue trigger a response in surrounding nerve fibers that are expressly designed to handle so-called “pain signals.” These fibers are said to fire “pain messages” toward the brain through a network in the spinal cord.

Before the brain receives these messages, a type of “gating” mechanism in a specific region of the spinal cord controls the duration and intensity of “pain signals” ultimately passed on to special parts of the brain. This gate is itself thought to be controlled by nerve impulses from all of the body’s five senses. Whatever “pain messages” the gate passes on become the raw material the brain uses to create the sensation of pain. Under the right circumstances, the gate can completely shut off all signals, resulting in no pain.

This interpretation of the so-called “spinal cord gate theory” is still the predominant concept of how pain works among many researchers and most physicians, and treatments of all pain are largely based on it.

However, Berkley and her colleagues–including Prof. P.D. Wall of London’s St. Thomas’s Hospital, one of the theory’s originators–argue that the gate theory has been grossly misrepresented. Wall has been a frequent visitor to Berkley’s group at FSU in recent years.

As Berkley explains it, the original gate theory refuted the idea that nerve fibers from the body handle so-called “pain messages.” What these fibers really do, she says, is deliver messages to the spinal cord–not about pain, but merely about stimulating events occurring to the body.

Once such information arrives at the spinal cord, it is subject to modification (“gating”) by interactions within the spinal cord itself and by information coming down from the brain, says Berkley. This modified information is then relayed to many parts of the brain where it gets modified even more by information arriving from other sensory organs. The final result may or may not be the perception of pain.

What this means, somewhat ironically, is that pain is a perceptual creation that is in fact always “in the head,” so to speak. What’s important, says Berkley, is that this means that injury or disease does not necessarily produce pain. And, conversely, pain can occur without any injury or threatening stimulus–ergo, an explanation for chronic pain that defies all efforts by physicians to pinpoint a cause.

Work by Berkley and her students at FSU, along with Wall and other colleagues in France and England, has extended the concept of how the brain creates the sensation of pain. Traditionally, neuroscientists thought that a particular nervous pathway identified years ago ferried information about gentle pressure on the skin to the brain. Berkley and her colleagues found that in fact this so-called “touch pathway” also carries information about both gentle and damaging events happening in internal organs.

This breakthrough discovery, published in the journal Nature Medicine in 1995, has considerably expanded scientists’ appreciation of the varied parts of the brain involved in creating the sensation of pain, says Berkley.

Because the brain is constantly receiving information from other organs, the picture it processes of what’s happening in the body is constantly changing as well, says Berkley. The upshot is that how the brain ultimately creates pain involves different “ensembles” of brain regions in different individuals at different times in their lives, she said.

Part two will be a continuation of Dr. Berkley’s work.

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