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[ Subject: ON PAIN'S TRAIL - Exploring fibromyalgia's mysteries
[ From: Dr. Jai Maharaj
[ Date: Tue, 23 Aug 2005

On pain's trail

Exploring fibromyalgia's mysteries, researchers look to
the central nervous system, gaining deeper insight into
why we suffer.

By Shari Roan, Times Staff Writer
The Los Angeles Times
Monday, August 22, 2005

For years, pain, stiffness and fatigue clung to Lauren
Armistead like an invisible shroud. It was tough enough
to live with fibromyalgia -- but the skepticism she
encountered when she discussed her condition was
intolerable.

"Throw out a word like fibromyalgia and you'll get this
blank stare," the 28-year-old said recently, sitting in
her Santa Monica apartment. "For so long, it was my own
private battle."

Today, however, Armistead is slowly, tentatively opening
up about a disease that is simultaneously emerging from
its own mysterious black box.

A groundswell of research has begun to expose the
underpinnings of the baffling disorder that affects an
estimated 6 million to 10 million Americans, most of them
women. Not only do the findings have the potential to
ease the condition's stigma, they also may provide clues
to other illnesses for which there is no clear clause.

Fibromyalgia, experts now believe, is a pain-processing
disorder -- arising in the brain and spinal cord -- that
disrupts the ways the body perceives and communicates
pain.

"There was a time when it was thought to be
psychosomatic," said Dr. Robert Bennett, a fibromyalgia
expert at Oregon Health & Science University in Portland.
"We now understand the pain in fibromyalgia is an
abnormality in the central nervous system in which pain
sensations are amplified."

Now doctors are more likely to acknowledge fibromyalgia
as a real illness. Because patients are being diagnosed
and referred to specialists more quickly, they're finding
relief, and acceptance, easier to come by.

Pharmaceutical companies have jumped on the new theory of
the disorder too. The first prescription drug approved
specifically for fibromyalgia will likely be approved
late next year or early in 2007, and at least half a
dozen pharmaceutical companies are developing other
treatments. Meanwhile, the federal government is funding
10 studies of the disease.

"It's very rewarding," said Dr. Stuart Silverman, medical
director of Cedars-Sinai Medical Center's Fibromyalgia
Rehab Program. "I was seeing patients before because no
one else wanted to see them. Patients would tell me,
'Everyone has told me there is nothing I can do.' "

*

The difficulty of diagnosis

Fibromyalgia typically is defined as unremitting pain in
multiple areas of the body -- at least 11 of 18 specific
tender points -- accompanied by fatigue, difficulties
with concentration and other vague physical discomforts.
The illness is called a syndrome because the cluster of
symptoms lacks the clear markers of disease, such as
changes in the blood or organ function.

Because patients often look healthy, doctors have
sometimes diagnosed fibromyalgia as a muscle problem or
an autoimmune disorder. It can also be a "wastebasket"
diagnosis, attached to people with inexplicable pain
problems. Some have even dismissed it as the complaints
of emotionally troubled women.

Many fibromyalgia patients stumble around for years
seeking help for their symptoms -- even after receiving a
diagnosis. Always athletic, Armistead first experienced
back pain when she was a child, but she assumed the
discomfort was a part of playing sports.

By the time she had joined the UCLA volleyball team in
the mid-'90s, however, Armistead knew something was
seriously wrong. After games, she would be racked with
pain. She sometimes took as many as 15 over-the-counter
pain pills a day.

Coaches and trainers, alarmed at her use of painkillers,
insisted she undergo medical tests. Over a year,
Armistead saw numerous doctors but got no answers.

"Eventually everyone started doubting whether or not I
was really in pain," she said. "My coach couldn't
understand how I could play one day and be bedridden the
next."

Debilitated by pain and fatigue, Armistead quit the team
and began to cut back on classes. She lost 35 pounds in
eight months. It was a time in her life "so painful, I've
tuned a lot of it out."

In 1996, however, a doctor diagnosed her problem as
ankylosing spondylitis, a type of arthritis affecting the
spine, and fibromyalgia.

Today Armistead takes an arthritis medication, two sleep
medications, vitamins and herbs. She undergoes
acupuncture, exercises moderately and works only a few
hours each day doing freelance marketing.

"With each passing year I've accepted the cards I've been
dealt," she said. "I'm not giving up. I keep trying new
treatments."

*

The evolution of treatment

Armistead, like many fibromyalgia patients, is a long way
from being pain-free. But the new research on
fibromyalgia's causes offers a blueprint for more
effective treatments.

For years doctors had been looking for a cause of
fibromyalgia at the site of the pain: the head, back,
hands, neck, gut or elsewhere. And their treatments
focused on soothing pain in these locations. As their
understanding has grown, however, these treatments have
begun to change and new ones are in development.

Fibromyalgia is now thought to arise from
miscommunication among nerve impulses in the central
nervous system, in other words the brain and spinal cord.
This "central sensitization" theory is described in
detail this month in a supplement of the Journal of
Rheumatology. The neurons, which send messages to the
brain, become excitable, exaggerating the pain sensation,
researchers have found.

As a result, fibromyalgia patients feel intense pain when
they should feel only mild fatigue or discomfort -- such
as after hauling bags of groceries. They sometimes feel
pain even when there is no cause.

"The pain of fibromyalgia is not occurring because of
some injury or inflammation of the muscles or joints,"
said Dr. Daniel Clauw, a fibromyalgia researcher and
director of the Center for the Advancement of Clinical
Research at the University of Michigan. "There is
something wrong with the way the central nervous system
is processing pain from the peripheral tissues. It's
over-amplifying the pain."

Recent studies show multiple triggers for the amped-up
response to pain. Fibromyalgia patients have, for
instance, elevated levels of substance P, a
neurotransmitter found in the spinal cord that is
involved in communicating pain signals.

They also appear to have lower levels of substances that
diminish the pain sensation, such as the brain chemicals
serotonin, norepinephrine and dopamine. Growth hormone,
which helps promote bone and muscle repair, is also found
in lower levels in fibromyalgia patients.

New therapies are aimed at these abnormalities. The
experimental drug pregabalin, for example, can reduce the
release of brain chemicals involved in the pain response.
Other medications might encourage the deep, restorative
sleep during which the body secretes growth hormone to
nourish tissues.

Although antidepressants that increase just serotonin
have been a disappointment in treating fibromyalgia, a
new class of drugs may provide better pain relief by
boosting both serotonin and norepinephrine. The pain and
depression of fibromyalgia are caused by abnormal levels
of these neurotransmitters, doctors now believe, not
simply by the inability to live life normally.

"What we have realized is there is a very strong
relationship between depression and pain
physiologically," Bennett said.

Medications approved specifically for fibromyalgia will
dramatically change treatment, Silverman predicts.

"Fibromyalgia will get a lot more respect," he said.
"People will think there must be a disease if there is a
medicine for it. It must be treatable."

*

A multifaceted model

The "central sensitization" model of fibromyalgia may
even be used to help explain and treat other chronic pain
conditions that have stumped doctors, such as irritable
bowel syndrome, chronic low back pain, interstitial
cystitis and vulvodynia, Clauw said. All may be
variations of central sensitization and the resulting
imbalance of chemicals and hormones.

Although fibromyalgia is thought to affect mostly women,
he believes many men are afflicted but are instead
diagnosed with chronic low back pain.

"These enigmatic chronic conditions are all probably
central pain syndromes," he said. "People were taught
that there is one kind of pain, a pain that occurs in the
area of the body where people are experiencing pain. But
this notion of central pain, that's where we really need
to move."

Others aren't so sure, however. Many questions about
central pain disorders remain, including why some people
are afflicted and not others; why symptoms can vary so
widely among patients; and whether the emerging chemical
markers -- high levels of substance P and low levels of
serotonin and norepinephrine -- cause the exaggerated
pain or are its result.

The central sensitization theory hasn't convinced
everyone that fibromyalgia is a real illness, said Dr.
Nortin M. Hadler, a professor of medicine, microbiology
and immunology at the University of North Carolina.

It's possible that fibromyalgia patients simply have a
different mind-set, he said. They tend to catastrophize
small burdens, exaggerate minor discomforts and quickly
lose hope. This psychic despair, he said, can alter
neurotransmitters and influence other central nervous
system functions.

"Is central sensitization something we want to label as a
pathological process or is this something we are all
capable of doing if we prepare ourselves intellectually?"
he said.

Hadler is the author of the 2004 book "The Last Well
Person," in which he said that too many normal human
characteristics and conditions are "medicalized" into
problems that require treatment.

Once fibromyalgia patients are treated as if they have a
disease, he said, "they never return to wellness."

*

A hard disorder to treat

This perception of fibromyalgia, while falling out of
favor among many doctors, nevertheless strikes a nerve in
patients and among doctors specializing in its treatment.

Fibromyalgia patients are difficult to treat, Bennett
said, requiring much time and attention. Some patients
never get better, although about 80% improve with a
dedicated treatment plan and lifestyle modifications, he
said.

"There is no recipe for treating fibromyalgia patients.
The treatments have to be fully individualized, and that
takes a lot of time," Bennett said. "Most patients aren't
getting the treatment they need."

Armistead, however, has reached a turning point. Now she
sits down with loved ones and friends and explains to
them, one on one, what her illness is like, how she must
be flexible when making plans, that she may not feel well
even though she looks fine.

"The name 'fibromyalgia' is recognized now," she said. "I
think someday people will be shocked that anyone thought
it was all in your head."

On a recent day, as the clock approached 6 p.m.,
Armistead pushed herself through a 90-minute yoga class
at a sunny Westside studio. She slowly picked up her mat,
towel and water and left the studio looking tired and
moving gingerly. Her back throbbed. Her neck hurt. A
headache was coming on.

But she did it. She made herself do the stretching
exercises her doctor said are necessary. She enjoys the
small satisfaction of knowing that she did her best.

"Living with any chronic illness is not easy," she said.
"It's a constant battle. My saving grace is I know there
will be a day when I'll wake up pain-free."

*

(BEGIN TEXT OF INFOBOX) New options for treatment

As understanding of fibromyalgia has grown, so too have
options for treating the condition. These medications are
under study:

o  Pregabalin (brand name Lyrica): This antiepileptic
drug, also approved for diabetic nerve pain, appears to
be effective in reducing pain and disturbed sleep in
fibromyalgia patients. If late-stage trials prove
successful, Pfizer plans to ask the FDA to approve the
drug for fibromyalgia.

o  Milnacipran: Marketed outside the United States as an
antidepressant, this drug increases the brain chemicals
norepinephrine and serotonin. Early studies showed it to
be successful in reducing fibromyalgia pain, and data
from the first phase-three trial is due out this fall.
Cypress Bioscience and Forest Laboratories hope to seek
FDA approval late next year.

o  Duloxetine (brand name Cymbalta): This
antidepressant, already on the market, increases the
activity of serotonin and norepinephrine. It was
successful in reducing fibromyalgia pain in early-phase
studies, and plans for a phase-three study are underway.
If successful, Lilly may seek FDA approval of the
medication for fibromyalgia.

o  Xyrem: Approved for narcolepsy with the complication
of weak or paralyzed muscles, the drug might be able to
increase deep sleep in people with fibromyalgia. The
results of an initial study on fibromyalgia are due later
this year. It's made by Jazz Pharmaceuticals.

o  Provigil: Approved for daytime sleepiness associated
with narcolepsy and shift-work disorders, or sleep
problems in those who work nights or on changing
schedules, the medication might help treat fatigue
related to fibromyalgia. The manufacturer, Cephalon Inc.,
has no plans to seek approval for the drug for this
purpose, but it can be used off-label.

o  Mirapex: Approved for Parkinson's disease, this drug
works by increasing the neurotransmitter dopamine. The
manufacturer, Boehringer Ingelheim, has no plans to study
the drug for use in fibromyalgia, but it can be used off-
label. An independent study showed it was promising for
reducing fibromyalgia pain.

- - -

Fibromyalgia's link to other disorders

The recent fibromyalgia research might also lead to a
greater understanding of several other disorders. The
suspected cause of the condition -- central
sensitization, in which nerve impulses in the central
nervous system malfunction -- may also play a role in:

o  Irritable bowel syndrome
o  Chronic fatigue syndrome
o  Gulf War syndrome
o  Interstitial cystitis
o  Vulvodynia
o  Chronic low back pain
o  Chronic headaches
o  Endometriosis

http://www.latimes.com/features/health/la-he-fibromyalgia22aug22,1,6467708.story
?track=mostemailedlink&ctrack=1&cset=true

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Posted on 8/22/2005 10:50:57 PM PDT in part by Plutarch
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