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The
Science of Pain 11/18/03 This is the second of a two part column on pain. Dr.
Darlyne Johnson, 46, an obstetrician-gynecologist at South Shore
Hospital in S. Weymouth, MA. is no stranger to pain – and not
just the pain of other women having babies. Over
the years, Johnson has had surgery, and each time, wound up with
such terrible nausea and vomiting from painkillers that she had to
stay in the hospital overnight. Not
surprisingly, when she found out three years ago that she needed
hernia surgery, she balked. “I knew what was going to happen –
I’d get sick.” Then
she heard about a device called ON-Q. It consists of a tiny tube,
placed in the incision and connected to a small container of local
anesthetic worn outside the body. Like water through a soaker
hose, the medication, usually lidocaine, oozes into the wound for
several days. The idea is that by blocking pain at the site of
injury, patients should need smaller doses of opioid painkillers,
which act on the whole body, often making people sick and spacey. “Basically, I was pain-free,” says a delighted Johnson, who immediately began offering ON-Q to her patients undergoing C-sections. And
that is just the beginning of doctors’ increasingly successful
efforts to manage pain. Chronic pain, which can be caused by damage to nerves (as in shingles or diabetes), inflammation (as in arthritis) and diseases (such as cancer), is a fact of life for 50 million Americans, according to some estimates, and as many as 75 million Americans, according to the American Pain Foundation, a consumer group. Another 25 million more suffer every year from acute pain after surgery or injury. At its
essence, pain “is an unpleasant and emotional experience
associated with tissue injury,” says anesthesiologist Dr. Daniel
Carr, professor of pain research at Tufts-New England Medical
Center in Boston. People can also feel pain when there is no
obvious tissue damage, as in fibromyalgia, or after a limb has
been amputated. Pain,
obviously, is an intensely subjective phenomenon. But there is
growing objective evidence of how pain is registered in the brain,
too. In one
recent report, Wake Forest University School of Medicine
researchers subjected volunteers to pain (heat) on their skin and
had them rate it on a scale of 0 to 10. They also scanned the
subjects’ brains with fMRI (functional magnetic resonance
imaging) and found that in those reporting the most intense pain,
several regions of the outer layer of the brain (the cortex) were
activated more often and more intensely. Dr. Catherine Bushnell, a professor of anesthesiology at McGill University, also uses brain scans to study pain. When people are distracted from pain, she has found, the scans reflect a dampened experience of pain, suggesting that a person’s psychological state can change the way pain is processed in the brain. On a
more technical level, pain comes in several forms. Nociceptive pain is triggered by tissue injury, including strong, noxious stimuli from the outside world such as a pin prick, heat or cold, as well as internal threats such as a kidney stone, obstructed bowe or infection. Neuropathic pain is caused by damaged nerves. Inflammatory pain is caused when joints or other tissues become swollen and release a cascade of natural, but harmful, chemicals. During transmission of pain signals from, say, a cut finger, to the brain, a slew of chemical signals is produced by injured tissues and nerves, including substance P, bradykinin and glutamate, which Dr. Clifford Woolf, a professor of anesthesiology research at Massachusetts General Hospital, calls “the star of the show.” At
normal levels, glutamate is essential to the functioning of the
nervous system; in excess, it can be devastating. When excess glutamate over-stimulates certain receptors on spinal cord neurons (called NMDA receptors), acute pain can be transformed into chronic pain. Some drugs already on the market such as ketamine and dextromethorphan can block this process. Researchers
now know that not only do all cells, including nerve cells, have
ion channels through which substances like sodium and calcium move
in and out, but that particular subtypes of sodium channels govern
the transmission of pain. “Some sodium channels are specific to
pain fibers,” says Woolf. This means that drugs targeted at only
these channels could block pain without affecting other cells. The
growing understanding of pain is the way pain is treated, says Dr.
James Rathmell, chairman of the committee on pain medicine for the
American Society of Anesthesiologists and a professor of
anesthesiology at the University of Vermont Medical College in
Burlington. One
example is sensitization, or “wind up” pain. When you injure
nerves in your finger, nerves in the spinal cord “reorganize to
amplify pain and remember it,” says Carr of Tufts. In other
words, acute pain becomes transformed into chronic pain. To
prevent this in surgical patients, some doctors now give patients
COX-2 inhibitors like Vioxx or Celebrex before surgery. These
drugs block an enzyme called cyclooxygenase-2, a key player in
pain transmission. For
women in labor, low doses of morphine injected into the
intrathecal space around the spinal cord provides “tremendous
pain relief,” Rathmell says. For
cancer pain, doctors also implant a permanent catheter (tiny tube)
into the intrathecal space and attach the tube to a morphine pump
placed in the abdomen. A major Johns Hopkins study showed that
this technique not only provides dramatic pain relief, but
increased longevity by a month or two. For
people with neuropathic pain, anti-epileptic drugs such as
Neurontin (gabapentin) are showing promise. The rationale is that
the body produces the same cascade of harmful chemicals during
both the “electrical
storm” of partial seizures and in neuropathic pain. Two
1998 studies showed that gabapentin can reduce nerve pain in both
diabetes and shingles. Other gabapentin-type drugs are now in
clinical trials for pain. For
people with back pain, microsurgery to remove damaged disks in the
spine can improve pain control significantly, says Dr. Michael
Ferrante, director of the UCLA Pain Management Center and
co-director of the UCLA Spine Center. So can non-surgical
techniques such as heated coils to destroy nerves in damaged
disks. Directly
addressing the link between chronic pain and depression can also
help, says Dr. Alan F. Schatzberg, chairman of the department of
psychiatry and behavioral sciences at Stanford University Medical
School. An epidemiological survey of 19,000 people in Europe shows
that there is a huge overlap between pain and depression. Anti-depressants
that boost both serotonin and nor-epinephrine, neurotransmitters
in the brain, seem to help with both pain and depression. Non-drug
approaches to pain control, most notably
acupuncture, can also be effective for some kinds of pain. As for
Dr. Darlyne Johnson and the ON-Q story?
One study by University of Vermont researchers on this
method of post-surgical pain control following knee surgery found
it had no effect. But the company that makes ON-Q, the I-Flow
corporation, says studies of patients undergoing hysterectomies or
colorectal surgery found that many patients using it needed less
then the usual level of opioids after surgery. At the
Johns Hopkins Hospital, anesthesiologists Dr. Lee Fleisher and Dr.
Christopher Wu are studying ON-Q in prostate surgery patients.
“We are very interested in seeing if there is a benefit to
blocking pain up front and never getting ‘wind up’ pain,”
says Fleisher. There’s no need to convince Dr. Darlyne Johnson of that. After her surgery, she went home quickly and needed only over-the-counter pain relievers: “It was a whole different experience.”
A
Conversation with Kathleen Foley
Dr.
Kathleen M. Foley, 59, spends most of her waking hours dealing
with two subjects that make many people cringe: pain, and death. As an
attending neurologist at Memorial Sloan-Kettering Cancer Center,
she treats the pain of cancer patients, including many who are
dying. As
director for the last nine years of the Project on Death in
America, an effort by George Soros’ Open Society Institute to
change the culture of death in this country, she’s been a
prominant voice for helping Americans get what polls show they
want: a dignified death, in many cases at home, with good pain
control and emotional support, for both patient and family. As
chair of three World Health Organization expert panels over the
last 27 years, she helped create
guidelines for doctors on managing cancer pain, setting up
palliative care services and controlling pain in children. A New
Yorker through and through, Dr. Foley was born and raised, with
her four sisters and two brothers, in Queens by her homemaker
mother and banker father. Though her mother died when Dr. Foley
was 13, she chugged straight through a Catholic girls’ school,
St. John’s University for a B.S. in biology, Cornell University
Medical College (now Weill Medical College of Cornell University)
for her M.D., and New York Hospital for her internship and
neurology residency. She has been at Sloan-Kettering ever since. Q. How
did you get interested in the subject of death and dying? A. I
was dragged into it. I was being interviewed for a position at
Sloan-Kettering to focus on pain in cancer. I told the interviewer
I knew nothing about pain. He said, ‘That’s okay. Nobody else
does, either.’ This was 1974. Researchers had just discovered
that there were receptors in the brain for painkillers, or
opiates. We knew
how to give morphine for acute pain, but we didn’t know how to
use it for chronic pain. It’s quite shocking to remember. Six
years after I got to Sloan-Kettering, we set up the first pain
service in the country for cancer patients. Q. In
the last five years, three major reports from the Institute of
Medicine (part of the National Academy of Sciences) have shown
that pain control is woefully inadequate. A 1995 study by the
Robert Wood Johnson Foundation showed that 50 percent of adults
die in pain. If we know so much about pain these days, why
aren’t we more aggressive about controlling it? A.
A big part of the problem is that our efforts to treat pain
aggressively have run into the war on drugs, as the furor over
opioids (or narcotics) like oxycodone [OxyContin] shows. Opioids
are safe and effective medications and patients can function very
well on them. But the increase in abuse of prescription opioids is
impacting the use of these drugs for legitimate medical problems.
Some drug stores won’t stock opioids. In some states, Medicaid
makes doctors get prior authorization before prescribing them.
Some doctors in New York – 30 percent in one survey – report
they are reluctant to prescribe them because of strict
regulations. Q. So,
what’s the solution? A. We need to balance our concerns about the risk of prescription drug abuse with the needs of pain patients. There are certain pain syndromes like neuropathic pain - pain resulting from injury to a nerve – for which current therapies work for less than half of the patients less than half of the time. We need to make pain research a national priority. Q. Why
don’t medical schools do a better job on all this? According to
a 2000-2001 survey of 125 medical schools compiled by the
Association of American Medical Colleges, only three percent had a
separate, required course on pain management and only four percent
had one in end-of-life care. The 2003 survey, which asked
questions differently, still shows only a few schools teaching
pain and palliative care as a separate course, though most do
include these issues to some extent in the curriculum. A. The
three Institute of Medicine reports identified lack of
professional education in pain and palliative care as the major
barrier to advancing these areas of expertise. Q.
Hospice care, usually in the patient’s home but also in nursing
homes, assisted living facilities and hospitals, is growing.
According to the National Hospice and Palliative Care
Organization, 11 percent of all deaths in 1993 took place in
hospice; by 2002, it was 28 percent. Yet polls show about 75
percent of Americans want to die at home. Why hasn’t the hospice
movement grown more? A. It’s complicated. To qualify for hospice benefits, a patient has to have about six months to live. But doctors have trouble prognosticating like that, especially for diseases other than cancer, such as Alzheimer’s disease and congestive heart failure. So people get to hospice late – when they have only a week or two to live. But the biggest issue is that in our culture, we don’t want to address death until it happens. Q. If
more people were in hospice or palliative care, wouldn’t that
save money? It must be cheaper to take care of someone at home
than in a hospital. A.
It’s probably at least cost-neutral. If we expand hospice to
non-cancer populations, we may shift costs from acute,
inappropriate care to appropriate, quality care. Q. In
many ways, palliative care seems like an ideal form of medicine.
Why do you have to be dying to get that kind of pain control and
emotional support? A.
Actually, we argue that palliative care should be an integrating
principle for both those at risk of imminent death and those with
chronic diseases. The
World Health Organization has it right – palliative care is an
approach to care for patients with life-threatening illnesses that
focuses on their quality of life. Q. If
we really had that, would we need physician-assisted suicide? A.
Probably not. Since Oregon passed its law in 1997, there have been
129 cases of physician-assisted suicide, although requests for a
doctor’s aid in dying have increased. The real issue is
providing palliative care for all Americans. At the present time,
we have not provided the education to health care professionals
and to the public about their real choices. Q. A
Canadian study three years ago showed that terminally ill cancer
patients who denied that they were dying were three times more
likely to be depressed than those who exhibited understanding of
their imminent deaths. Do you think talking about death helps? A.
There is a distinction between people knowing they are going to
die soon and their being willing to talk about it. Many people
know, but don’t wish to articulate it. Some don’t need to talk
about it. But you don’t have to force someone to talk about it
to be helpful. I am most humbled by all of this. What you can ask
is ‘What do you know about your situation? What are you worried
about? And how can we help.’ Q. So
what is your definition of a “good death?” A .
It’s a good death is if the patient has what he or she wanted
– having the family there, if that’s what they wanted, or not,
if it’s not. It’s not suffering in the last days or hours or
minutes. It’s having an opportunity to say goodbye, if that was
something they valued. And it’s being recognized as the person
they have been.
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