PAIN, THE DISEASE

A modern chronicler of hell might look to the lives of chronic-pain
patients for inspiration. Theirs is a special suffering, a separate
chamber, the dimensions of which materialize at the New England Medical
Center pain clinic in downtown Boston. Inside the cement tower, all sights
and sounds of the neighborhood -- the swans in the Public Garden, the
lanterns of Chinatown -- disappear, collapsing into a small examining room
in which there are only three things: the doctor, the patient and pain. Of
these, as the endless daily parade of desperation and diagnoses makes
evident, it is pain whose presence predominates.

"Yes, yes," sighs Dr. Daniel Carr, who is the clinic's medical director.
"Some of my patients are on the border of human life. Chronic pain is like
water damage to a house -- if it goes on long enough, the house collapses.
By the time most patients make their way to a pain clinic, it's very late."
What the majority of doctors see in a chronic-pain patient is an
overwhelming, off-putting ruin: a ruined body and a ruined life. It is
Carr's job to rescue the crushed person within, to locate the original
source of pain -- the leak, the structural instability -- and begin to
rebuild: psychically, psychologically, socially.

For leaders in the field like Carr, this year marks a critical watershed.
In January, the Joint Commission on Accreditation of Healthcare
Organizations, the basic national health care review board, implemented the
first national standards requiring pain assessment and control in all
hospitals and nursing homes. Standards for evaluating and managing pain in
lab animals have long been tightly regulated, but curiously there had never
before been any legal equivalent for people. Maine took the further step
last year of passing its own legislation requiring the aggressive treatment
of pain, and California and other states are considering following suit.

"It's a field on the verge of an explosion," Carr says. "There's no area of
medicine with more growth and more public interest. We've come far enough
scientifically to see how far we have to go."

Chronic pain -- continuous pain lasting longer than six months -- afflicts
an estimated 30 million to 50 million Americans, with social costs in
disability and lost productivity adding up to more than $100 billion
annually. However, only in recent years has it become a focus of research.
There used to be no pain specialists because pain had always been
understood as a symptom of underlying disease: treat the disease and the
pain should take care of itself. Thus, specializing in pain made no more
sense than specializing in fever. Yet the actual experience of patients
frequently belied this assumption, for chronic pain often outlives its
original causes, worsens over time and appears to take on a puzzling life
of its own.

Research has begun to shed light on this: unlike ordinary or acute pain,
which is a function of a healthy nervous system, chronic pain resembles a
disease, a pathology of the nervous system that produces abnormal changes
in the brain and spinal cord. New technology, like functional imaging,
which is generating the first portraits of brains in action, is revealing
the nature of pain's pathology.

Far from being simply an unpleasant experience that people should endure
with a stiff upper lip, pain turns out to be harmful to the body. Pain
unleashes a cascade of negative hormones like cortisol that adversely
affect the immune system and kidney function. Patients treated with
morphine heal more quickly after surgery. A recent study suggests that
adequate cancer-pain treatment may influence the prospects for survival:
rats with tumors given morphine actually live longer than those that do not
receive it.

Paradigm shifts occur slowly; if arriving at a new medical conception of
pain has been difficult and protracted, disseminating the knowledge will be
more so. Pain treatment belongs primarily in the hands of ordinary
physicians, most of whom know little about it. Less than 1 percent of them
have been trained as pain specialists, and medical schools and textbooks
give the subject very little attention. The primary painkillers -- opiates,
like OxyContin -- are widely feared, misunderstood and underused. (A 1998
study of elderly women in nursing homes with metastatic breast cancer found
that only a quarter received adequate pain treatment; one-quarter received
no treatment at all.)

While the undertreatment of pain has led to lawsuits -- recently, a
California court issued a judgment against a Bay Area internist for
undertreating a terminally ill patient's cancer pain -- so has the
overprescribing of OxyContin in cases of patient abuse. It takes only a few
lawsuits -- along with the threat of Drug Enforcement Administration
oversight and regulation -- to exert a chilling effect on prescribing
practices. "Doctors feel damned if they do and damned if they don't," says
Dr. Scott Fishman, chief of the division of pain medicine at the University
of California at Davis Medical Center. "The enormous confusion about pain
has led to the hysteria around opiates."

Dr. James Mickle, a family doctor in rural Pennsylvania, describes the
leeriness most physicians feel about treating pain: "Is it objective or
subjective? How do you know you're not being tricked or taken advantage of
to get narcotics? And chronic-pain patients are, generally, well -- a pain.
Most doctors' reaction to a patient with chronic pain is to try to pass
them off to someone who's sympathetic."

And what makes a doctor sympathetic to pain?

"Someone who has pain himself," Mickle says. "Or has an intellectual
interest -- who isn't interested in immediate results, doesn't want to make
money, has a lot of degrees. There's one in a lot of communities, but then
they get all the pain patients sent to them and eventually they burn out
and quit."

Daniel Carr's interest in pain began as an intellectual one. After training
as an internist and endocrinologist, he published a landmark study in 1981
of runners, which showed that exercise stimulates beta-endorphin
production, leading to a "runner's high" that temporarily anesthetizes the
runner. He began to wonder: if the runner's high is an example of how a
healthy body successfully modulates pain, what abnormality leads to chronic
pain? He did a third residency in anesthesia and pain medicine, became a
founder of the multidisciplinary pain clinic at Massachusetts General
Hospital and a director of the American Pain Society. Six years ago, he
moved to Tufts and set up a pain clinic (which loses money) and created the
country's first master's program in pain for health professionals.

Every pain patient is a testament to the dangers of the conservative
wait-it-out approach to pain, as a day spent in Carr's clinic demonstrates.
But it is the last patient of the day, Lee Burke, whose story proves the
most instructive, because her diagnosis turns out to be so simple, while
the forces that worked against it being made earlier were so complex.

Doctors warn patients of many risks, from death to scarring, but rarely
mention the not-uncommon side effect of chronic pain. The life of one of
Carr's patients was ruined by having a nerve nicked during plastic surgery
to correct protruding ears. Another acquired chronic chest pain after being
treated in a hospital for a collapsed lung when a tube was inserted in her
chest -- one of the most nerve-rich areas in the body. One especially
poignant category of patients in pain clinics is that of those who have had
surgery specifically to treat chronic -- usually back -- pain where the
surgery leads to new, worse pain, an outcome for which they say they had no
warning.

Pain doctors have many theories about why these kinds of things happen, but
the dialogue is frustratingly one-sided. There are no spokesmen for
undertreating pain -- no one advocates not treating pain.

Although I contacted many of the former doctors of pain patients, it was
rare that one was willing to examine his decisions thoughtfully, as Martin
Acquadro did. It was immediately clear to me that Acquadro, a licensed
dentist as well as an anesthesiologist, was both competent and caring and
that the forces that delayed Burke's treatment were not personal
shortcomings but genuine, pervasive confusions about pain.

Acquadro thought the pain of all acoustic neuroma patients should manifest
itself similarly, and most of those he had seen did, in fact, "respond to
simpler, more holistic therapies." He had not thought of Neurontin, and he
feared opiates. "We don't always do patients a favor putting them on
high-dose narcotics," he says. "When a patient is depressed or anxious,
you're leery about narcotics or alcohol. With Lee, I guess I'd have to say
I was being cautious." His voice changes -- softens and quiets -- as he
gets to the real point: "I was afraid."

Like many doctors, he says he felt comfortable with anti-inflammatory
drugs, although the 3,200 milligrams of ibuprofen that Burke took daily put
her at risk for gastrointestinal bleeding. According to the Federal Drug
Abuse Warning Network, anti-inflammatory drugs (including aspirin and
Aleve) were implicated in the deaths of 16,000 people in 2000 because of
bleeding ulcers and related complications. While large doses of the drugs
are sometimes needed to treat inflammation, opiates are a much safer -- and
generally more effective -- analgesic.

Although far fewer than 1 percent of pain patients using opiates develop
any addictive behavior, opiates have a reputation for being dangerous, and
social biases -- class, race and sex -- influence who is entrusted with
them. Studies by Dr. Richard Payne at Sloan-Kettering show that minorities
are up to three times as likely as others to receive inadequate pain relief
- -- and to have their requests for medication interpreted as bad
"drug-seeking behavior." A study conducted by Dr. William Breitbart at
Sloan-Kettering found that women with H.I.V. are twice as likely to be
undertreated for pain as men. Many of Carr's patients have some social
strike against them that led their previous doctors to withhold treatment:
two were workers' compensation cases, one was mentally ill, several had
histories of substance abuse, all of them were poor and most were women.

Women tend to be either less aggressive in demanding pain treatment or to
be aggressive in ways that are misinterpreted as hysteria. The longer pain
goes untreated, the more desperate and crazed the patient becomes -- until
those behaviors look like the problem. Burke recalls that whenever Acquadro
sent her to other specialists -- headache specialists, balance specialists
and behavioral pain-medicine specialists -- she would break down during the
appointments in pain and frustration. "They all just figured I was a basket
case," she says. "And I was. I was a basket case."

Rather than dismiss her psychic distress, Acquadro seems to have become
overly focused on it, trying to explain her pain through that prism: "Lee's
pain seemed to be better at the times she was happier, was forming new
relationships or helping others," he says. "And even though she was
motivated and worked hard on stress reduction, the fact remains, she is a
tense person."

Naturally. Everyone who has chronic pain eventually develops anxiety and
depression. Anxiety and depression are not merely cognitive responses to
pain; they are physiologic consequences of it. Pain and depression share
neural circuitry. The hormones that modulate a healthy brain, like
serotonin and endorphins, are the same ones that modulate depression.
Functional-imaging scans reveal similar disturbances in brain chemistry in
both chronic pain and depression.

"Chronic pain uses up serotonin like a car running out of gas," says
Breitbart. "If the pain persists long enough, everybody runs out of gas."
Thus, Acquadro's not treating Burke's pain aggressively because she was
"tense" is like "not rescuing someone who is drowning because they're
having a panic attack," according to Breitbart. Difficulty breathing
triggers panic as reliably as pain causes depression. When serotonin is
inhibited in laboratory animals, morphine ceases to have an analgesic
effect on them. Medications that treat depression also treat pain.
Depression or stressful events can in turn enhance pain. Since Sept. 11,
pain clinics have been fuller. "If we started putting sugar in the water,
it would affect the diabetics first -- pain patients respond to stress with
increased pain," explains Scott Fishman, who also trained as a
psychiatrist. But to make stress reduction a primary strategy for pain
treatment is trying to repaint the walls of a crumbling house.

It is an easy mistake to make -- and one I made myself. i developed pain
five years ago for, what seemed to me, absolutely no reason. A fiery
sensation flared in my neck, flowed through my right shoulder and sizzled
in my hand. It didn't feel like normal pain -- it felt like a demon had
rested a hand on my shoulder. Suddenly I tasted brimstone and burning.

Two years later, an M.R.I. would reveal spinal stenosis, a narrowing of the
spinal canal, and cervical spondylosis, a type of arthritis, both of which
squeeze the nerves and cause pain to radiate into my shoulder and hand. But
in the meantime, I was convinced that if I steadfastly ignored it, the pain
would eventually go its own way. I tried to treat it as a psychological
problem. Many pain patients have had doctors who pathologized them, told
them their pain was unreal; I pathologized myself, hoping my pain was
unreal -- or that it would become so if I treated it as such.

I analyzed the pain in psychotherapy. I tried acupuncture, massage and
herbal remedies. I read books about conversion hysteria, the placebo effect
and Sufis who thread fishhooks through their pectoral muscles. What I
didn't read was anything that might have actually informed me about my
symptoms, like Fishman's excellent patient-oriented book, "The War on
Pain." Nor did I consult any clarifying Web sites, like painfoundation.org.

When the pain depressed me, I focused on the depression. I adopted Dr. John
E. Sarno's popular creed that muscular tension syndrome is the source of
most back ills and faithfully scrutinized my life for stress. It is one of
those circular self-confirming hypotheses: when I was happy and my pain
light, I took it as confirmation of the correlation; when I was happy but
had a lot of pain, I wondered if I didn't want to be happy. I recall how,
strapped inside the white crypt of the M.R.I. machine for more than an
hour, I tried to calm myself by repeating the motto of my Christian
Scientist grandparents: "There is no life, truth, intelligence nor
substance in matter. All is infinite Mind and its infinite manifestation."
But I sensed the machine was seeing my pain in its own way and that its
report would be irrefutable. My pain would no longer be a tree falling in
the forest with no one to hear it. The greatest fear pain patients have,
doctors sometimes say, is that it is "all in their heads." But infinitely
scarier, I thought as I lay there, is the fear that it isn't.

This is the new frontier of medicine," Clifford Woolf says heatedly in his
clipped South African accent. "What we're learning is that chronic pain is
not just a sensory or affective or cognitive state. It's a biologic disease
afflicting millions of people. We're not on the verge of curing cancer or
heart disease, but we are closing in on pain. Very soon, I believe, there
will be effective treatment for pain because, for the first time in
history, the tools are coming together to understand and treat it."

The most important tool in his lab at Mass. General -- a vast landscape of
test tubes filled with rat DNA -- is the new "gene chip" technology that
identifies which genes become active when neurons respond to pain. "In the
past 30 years of pain research, we've looked for pain-related genes, one at
a time, and come up with 60. In the past year, using gene-chip technology,
we've come up with 1,500," Woolf says happily. "We're drowning in new
information. All we have to do is read it all -- to prioritize, to find the
key gene, the master switch that drives others."

Woolf is particularly interested in certain abnormal sodium ion channels
that are only expressed in sensory neurons that have been damaged. He
believes he is close -- perhaps a year away -- from identifying which among
these channels is the most important one. Then -- if his animal data
applies to humans -- pharmaceutical companies could design blockers for
these channels, and after the years it takes to develop a new drug, there
could be a cure for neuropathic pain.

On the table before us in Woolf's lab, a graduate student is piercing the
sciatic nerve of a white rat. The rat is of a pain-sensitive variety, one
prone to developing neuropathic pain. In 10 days, when Woolf cuts open the
rat's brain, he will be able to discern the imprint of the sciatic nerve
injury. There will be corresponding maladaptive changes in the way the
brain processes and generates pain.

The biggest question of pain research is whether this pathological cortical
reorganization can be undone. A 1997 University of Toronto study has shown
disturbing implications. Anna Taddio compared the pain responses of groups
of infant boys who had been circumcised with and without anesthesia. Four
to six months later, the latter group had a lowered pain threshold, crying
more at their first inoculations -- providing evidence that there is
cellular pain memory of damage to the immature nervous system.

Terms like "pathological cortical reorganization" and "cellular pain
memory" have a very ominous ring. Are these children really doomed to be
more sensitive to pain their entire lives? Will a cure for neuropathic pain
help all the people who already have it -- or only prevent others from
developing it?

Woolf looks at me and hesitates. "We don't really know," he says tactfully.
Another pause. "In the present state, no." However, he says, even if the
damage cannot be undone, treatment could still help suppress the abnormal
sensitivity. "But obviously, it's going to be much easier to prevent the
establishment of abnormal channels than to treat the ones already there."
He sighs, rests his head against his hand. "Obviously."

I want to ask another question, but I'm overcome by a rare unreporterly
desire. I want him to get back to work.