Thursday, January 31, 2008

Pitching Relief: A Physician With Firsthand Knowledge About Pain Advocates Opium-Based Drugs Despite Fears of Abuse

Pitching Relief
A Physician With Firsthand Knowledge About Pain Advocates Opium-Based Drugs Despite Fears of Abuse

By Marc Kaufman
Washington Post Staff Writer
Sunday, April 23, 2006

Howard Heit knows pain.

He lives it, he studies it, he works to reduce it. His own pain used to get so bad that he wore patches of hair off the back of his head by rubbing it hard against walls in a desperate effort to get some relief.

"What I was feeling was like a cramp in my leg, but multiply that by 100 times and make it continuous," he now says. He no longer hurts like that, but he still wears a brace with a head attachment he can push against for acupressure when a pain spasm hits.

Heit is a doctor. Today he's a pain and addiction specialist in Fairfax, but once he was an up-and-coming gastroenterologist, a football player, a jock. That was before his auto accident, the one that changed his life and taught him about pain problems the very hard way -- as a patient who often didn't get the help he so badly needed.

The doctor still spends a lot of time in his wheelchair, but that hasn't stopped him from becoming a prominent practitioner and lecturer over the past decade. More recently, his profession and personal history have propelled him to the center of a contentious national dispute that he virtually personifies.

On one side, the Drug Enforcement Administration and Justice Department -- alarmed by the seemingly widespread diversion of opium-based prescription drugs such as OxyContin and Dilaudid to addicts and abusers -- have investigated, arrested and prosecuted as "drug dealers" scores of pain doctors who allegedly misused their authority to write prescriptions for narcotic painkillers. On the other side, many pain doctors and patients have protested the DEA's approach as overly aggressive and punitive, saying that it's unfairly penalizing pain patients.

Heit, 61, doesn't use prescription opioids for his own pain now, but he does prescribe them in high doses to many of his patients, and he's seen the drugs (in conjunction with proper monitoring) provide remarkable relief -- the kind he still wishes he had had available back when he really needed it. As the showdown between pain doctors and prosecutors stiffened several years ago, he felt obliged to get more actively involved in defense of opioid treatment despite the potential risk to his practice.

So he joined a team of 18 pain and addiction specialists, hospice and cancer-care workers and DEA officials to write and review guidelines for the proper prescribing of narcotics. He was delighted when, after more than two years of work, their Frequently Asked Questions presentation was posted on the DEA Web site in the summer of 2004. But several weeks later the FAQs disappeared from the site and was soon essentially repudiated by the agency, leading 30 state attorneys general to write to the agency in protest. The chill in the world of pain management has grown worse ever since.

More ...


Wednesday, January 30, 2008

Swiss study in mice may lead to new pain drugs | Reuters

CHICAGO, Jan 16 (Reuters) - Enhancing a natural pain-filtering mechanism in the spine helped relieve chronic pain in mice without the unwanted side effects of current pain relievers, Swiss researchers said on Wednesday.

They honed in on a specific molecule that helps prevent chronic pain signals from reaching the brain, without blocking normal pain messages that alert people to danger.

And they said their experiments in mice may point the way to better drugs in humans.

"Our approach addresses primarily chronic pain," said Hanns Zeilhofer of the University of Zurich in an e-mail.

He said analgesics such as aspirin can cause stomach ulcers, while opioids such as morphine make patients sleepy and are addictive.

Zielhofer's idea was to find a way to trick the body into intercepting pain signals before they cause havoc in the brain.

"We know that normally the spinal cord acts as filter for pain signals. It prevents most of the pain signals from reaching the brain, where pain becomes conscious," said Zeilhofer, whose study appears in the journal Nature.

Zeilhofer's team focused on a molecule called GABA that that can inhibit pain signals.

A class of drugs called benzodiazepines, which include diazepam -- better known as Valium -- bolsters the action of this GABA molecule in the central nervous system. The drugs are used to treat things like anxiety and insomnia, but when injected near the spine, these drugs also relieve pain.

"Problem is, they must not be used in chronic pain patients because of undesired effects that they have in the brain," Zeilhofer said in an e-mail. "They make patients sleepy, they impair memory and can cause addiction." But benzodiazepines target at least four different GABA receptors that mediate pain control.

"These receptors turned out to be predominately present in the spinal cord and occur in the brain at much less density," he said. By targeting just two of the GABA spinal receptors, they might be able to make a drug that could be used for chronic pain without losing potency or making people sleepy.

To test this, the researchers used genetically engineered mice to target only the GABA receptors in the spine. Then they irritated nerves in the paws of mice, making them more sensitive to touch and measured how fast the mice pulled away when gently touched.

"When we treated the mice with the right drugs, their sensitivity to this touch became normal again," Zeilhofer said. And it worked without unwanted sedation or impaired motor function.

"Normal pain, however, was retained. This is important because normal pain has a protective function as it warns us of tissue damage," he said. They also used brain scans on rats to see how the drugs worked in certain pain centers that control both the sensation of pain and the feelings of anxiety that pain can produce. The scans showed the drugs reduced pain in these brain regions. Zeilhofer said the study showed that targeting specific GABA receptors may provide a promising new target for drug development. "The next big challenge will be to develop drugs which work in humans," he said.

The Best of January’s Pain Articles | How To Cope With Pain Blog

How to Cope with Pain is now offering a monthly Pain-Blog Carnival during the last week of every month, to include each month's best posts.  January's carnival is now posted.  New bloggers are always welcome to contribute.

Tuesday, January 29, 2008

Emergency room - pain rating scales

Comedian Brian Regan goes into detail about the ER

Strange Creature Immune to Pain | LiveScience

Strange Creature Immune to Pain

By Charles Q. Choi, Special to LiveScience

As vulnerable as naked mole rats seem, researchers now find the hairless, bucktoothed rodents are invulnerable to the pain of acid and the sting of chili peppers.

A better understanding of pain resistance in these sausage-like creatures could lead to new drugs for people with chronic pain, scientists added.

Naked mole rats live in cramped, oxygen-starved burrows some six feet underground in central East Africa. Unusually, they are cold-blooded — which, as far as anyone knows, is unique among mammals.

"They're the nicest, sweetest animals I've ever worked with — they look frightening, but they're very gentle," said neurobiologist Thomas Park at the University of Illinois at Chicago

Scientists knew the mole rats were quite sensitive to touch — perhaps to help replace their almost useless eyes. After probing their skin, Park and his colleagues unexpectedly discovered the rodents lacked the chemical Substance P, which causes the feeling of burning pain in mammals.

Acid t

The researchers discovered that when unconscious mole rats had their paws injected with a slight dose of acid, "about what you'd experience with lemon juice," Park said, as well as some capsaicin — the active ingredient of chili peppers — the rodents showed no pain.

"Their insensitivity to acid was very surprising," Park told LiveScience. "Every animal tested — from fish, frogs, reptiles, birds and all other mammals — every animal is sensitive to acid."

To explore their pain resistance further, the researchers used a modified cold sore virus to carry genes for Substance P to just one rear foot of each tested rodent. Park and his colleagues found the DNA restored the naked mole rats' ability to feel the burning sensation other mammals experience from capsaicin.

"They'd pull their foot back and lick it," Park said. Other feet remained impervious to the sting of capsaicin.

"Capsaicin is very specific for exciting the fibers that normally have Substance P," Park added. "They're not the fibers that respond to a pinprick or pinch, but the ones that respond after an injury or burn and produce longer-lasting pain."

Curiously, the researchers found that mole rats remained completely insensitive to acids, even with the Substance P genes. This suggests there is a fundamental difference in how their nerves respond to such pain.

"Acid acts on the capsaicin receptor and on another family of receptors called acid-sensitive ion channels," Park said. "Acid is not as specific as capsaicin. The mole rat is the only animal that shows completely no response to acid."

Why so i

Scientists theorize naked mole rats evolved this insensitivity to acid due to underground living. The rodents exhale high levels of carbon dioxide, and in such tight, poorly ventilated spaces it builds up in tissues, making them more acidic. In response, the mole rats became desensitized to acid.

"To give you an idea of what they experience, we normally all breathe in carbon dioxide levels of less than 0.1 percent. If people are exposed to an air mixture with as low as 5 percent carbon dioxide, we'll feel a sharp, burning, stinging sensation in our eyes and nose," Park said. "We hypothesize that naked mole rats live in up to 10 percent carbon dioxide."

Researcher Gary Lewin, a neuroscientist at the Max Delbrück Institute for Molecular Medicine in Germany, noted, "People may say, 'So what — it's weird, but what has it to do with human pain?' I think that is wrong, unimaginative and short sighted."

Lewin noted that all vertebrate pain-receptor systems "are built in a highly similar way, so the mole rat may tell us how you can unbuild the system."

Help for people

Specifically, Park noted this research adds to existing knowledge about Substance P. "This is important specifically to the long-term, secondary-order inflammatory pain. It's the pain that can last for hours or days when you pull a muscle or have a surgical procedure," he explained.

As such, these findings might shed new light on chronic pain. Park said,

"We're learning which nerve fibers are important for which kinds of pain, so we'll be able to develop new strategies and targets."

Lewin added, "We really do not understand the molecular mechanism of acid sensing in humans, although it is thought to be pretty important in inflammatory pain. An animal that naturally lacks such a mechanism may help us identify what the mechanism actually is."

Park next plans to study distantly related animals that dwell in similar circumstances, such as the Mexican free-tailed bat and the Alaskan marmot, which both spend large amounts of time in high carbon dioxide caves or burrows. "How are they surviving down there? It'd be interesting if we saw some parallels there with the naked mole rats," Park said.

The scientists detailed their findings online Jan. 28 in the journal PLoS Biology.

SIMPLY WAIT - a personal blog by writer Patry Francis

Yesterday, for the first time in weeks, I got dressed in real clothes: my too-big jeans and a sweater. I put on boots and make-up. I found out what the weather was like by feeling it against my skin, instead of asking my family as they swept in from their busy lives. (It was COLD, wonderfully, slap in the face cold.)

I was out in the world and life was good--even if my only destination was the doctor's office in Boston.

I enjoyed traveling through the snow squalls on the Cape. Even when my daughter-in-law, Nicola, took the wrong exit, we celebrated being lost--pointing out the architecture, and imagining how exciting it would be to live in some of the neighborhoods we passed.

"Someday, when everyone's on their own, I'd like to move to the city," I said, daring to imagine the future.

When we passed the river, Nicola said she particularly loved Boston because the Charles reminded her of the river that cut through her native Melbourne.

We also acknowledged that if we'd been with our spouses, we would have been enjoying the scenery less and blaming each other for screwing up the directions more...

We got there on time, but even if we hadn't, it would have been okay. Some days, I've sat in the waiting room for more than two hours before I heard my name called. It turned out yesterday was one of those days.

"Simply waiting" in the Cancer Center wasn't easy. The fifteen or twenty people who sat in chairs along the periphery all looked scared and tense. No one spoke. Furtively, I checked out them out, wondering what form of the disease they had, what their prognoses might be. Were they among the statistical numbers who would beat the disease? Was I?

The first day I visited, most of the patients were a generation older than I was. What was I doing there? I wondered. It wasn't fair. Then I spotted a woman who appeared to be about the age of my oldest son. Damn. Cancer WASN'T fair. It wasn't democratic. It just was.
I looked down and pretended to read People magazine.

This time, however, Nicola and I had eight month old Hank with us. How would an active, squirmy baby ever endure the kind of wait that drove adults to distraction? But it turned out that Hank found the spacious waiting room perfect for exploring on hands and knees, the coffee tables just the right height to walk around, and the seats filled with people he was eager to meet.

He started with those closest to us, and then, slowly (followed by his mum, of course) he extended his reach to everyone in the waiting room, transforming the atmosphere as he crawled around, babbling and smiling.

Strangers smiled back and called to him, "Over here, buddy." When he toppled over, people leaped up to make sure he was all right. Suddenly, Nicola and I weren't the only ones watching to make sure he didn't put anything in his mouth. Everyone in the room had his back.

Soon people were sharing stories about their children and grandchildren. When someone said that babies who don't crawl before they walk often have developmental delays later, a vigorous debate broke out.

Eventually, the conversation expanded. People discussed how far they'd traveled to get there, and worried that they'd get on the road before rush hour. A couple of men started to talk about sports.

We stopped being a bunch of solitary, anxious cancer patients, and became a room full of human beings. I forgot to think about how many paients had come in after me and heard their names called before me, or to look at my watch. What remained was the goodwill in that room, the outstretched hands, and the encouraging words to Hank when he took a couple of tentative steps between table and chair.

"Look! You're doing great. You can do it!"

On the way home, exhausted, but strangely elated, I wondered why it took a baby to release us from our fear and reveal our common humanity....

And why it took a life-threatening illness to make me realize that nothing is promised to me or to anyone else--not a single breath--that it's all a gift and I'd better savor every bit of it--even the missed exits, and the unexpected detours.

Friday, January 25, 2008

Rein on pain lays mainly in the brain, researchers find

Chronic pain sufferers may be able to reduce pain levels by studying their own live brain images, researchers at the School of Medicine report in a new study.

With training in an investigational technique called "neuroimaging therapy" and the use of high-tech imaging equipment, subjects were able to influence their pain by controlling activity in one of the pain centers of the brain through the use of mental exercises and by visualizing their own brain activity in real time.

Compare it to exercising your muscles in a top-of-the-line weight room. After repeated practice, you get better at it.

The scientists are hopeful that the new technique will be used in the future as a long-term treatment for chronic pain patients—possibly even without all the high-tech equipment. They caution that significantly more work is needed before it can be thought of as a clinical treatment. "We believe these subjects and patients really learned to control their brain and, through that, their pain," said Sean Mackey, MD, PhD, assistant professor of anesthesia and co-author of the study in the Dec. 12 online issue of the Proceedings of the National Academy of Sciences.

The study posed two questions: "Can healthy subjects and patients with chronic pain learn to control activity in specific regions of their brain? And, in doing so, does this lead to an improved control of their pain?" The answer to both was a resounding: "Yes."

"I got incredibly jazzed by the results," said Mackey, who is also associate director of the medical center's pain management division. "However, significantly more science and testing must be done before this can be considered a treatment for chronic pain." A second, larger study is under way to test the potential for long-term use in future therapy.

The researchers used a new technology called real-time functional magnetic resonance imaging, or rtfMRI. The scientists placed subjects inside an MRI scanner where they were able to watch the subjects' brain activity on a moment-by-moment basis. The subjects were then shown "live" action images of their rostral anterior cingulate cortex, an area of the brain responsible for processing pain.

Next, subjects and patients were asked to try various mental strategies to change their brain activity. "As an example, we asked them to think about changing the meaning of the pain," Mackey said. "Instead of thinking of it as a terrible experience, to think of it as something relatively pleasant. Over time, subjects showed an increased ability to change their brain and by doing so to modulate their pain."

How did they do it exactly? "We really don't know, but then we really don't know how anyone controls their brain to perform an action," Mackey said.

Laura Tibbitts, 31, a subject in the study who suffers from back pain caused by a horseback riding accident seven years ago, said she used different thoughts to decrease the pain while watching her "brain on pain."

"I'd think of little people on my back digging out the pain, or I'd think of snowflakes," she said. "The goal was to exercise your brain, to retrain it. Sometimes I felt like I had made a change in my brain. The pain was never completely gone, but it was better."

Mackey said extensive controls were used in the study to make sure the results reflected a direct correlation between brain imaging and pain control.

"One of the questions that always comes up is, 'Did we just design the world's most expensive placebo?'" Mackey said. Researchers used multiple control groups to ensure against this: The first remained outside the MRI machine; the second received no imaging feedback; the third was shown different areas of the brain that don't process pain; and members of the fourth group were shown someone else's brain activity. None of the control subjects showed an ability to control pain levels.

"Real-time functional neuroimaging is a wonderful tool for investigating the neurosystems in the brain responsible for the perception and processing of pain," Mackey said. "It allows us to do that in ways that we've never been able to before."

Training Your Brain to Handle Pain - video

Training Your Brain to Handle Pain
Scientists are finding that it truly is the brain that decides what is or isn't painful. They're also finding that there may be a way to teach people to train their brain to better handle chronic pain.

Wednesday, January 23, 2008

Medical News: NSAIDs, Acetaminophen Equivalent in Relieving Low Back Pain - MedPage Today

ROTTERDAM, The Netherlands, Jan. 23 -- For lower back pain, the old standby acetaminophen appears to be as effective for pain relief as nonsteroidal anti-inflammatory drugs (NSAIDs), researchers here said.

A meta-analysis of 65 studies of NSAIDS for lower back pain, with or without sciatica, showed the drugs are more effective than placebo but roughly equivalent to acetaminophen, according to a systematic review published in the first 2008 issue of The Cochrane Library.

But NSAIDs have significantly more side effects -- mainly gastrointestinal -- than acetaminophen, with a relative risk of 1.76 (with a 95% confidence interval from 1.12 to 2.76), the researchers found.

The findings support guidelines that suggest NSAIDs be used only after acetaminophen (also known in Europe as paracetamol) has been tried, "since there are fewer side effects with paracetamol," said lead author Pepijn Roelofs, a doctoral student at Erasmus University in Rotterdam, Holland, and colleagues.

The report is an undated version of a review first published in 2002. It includes 15 new studies, the researchers said. Of the 65 evaluated studies, which enrolled 11,237 patients, 28 (or 42%) were considered high quality.

The 65 studies compared NSAIDs to placebo, acetaminophen, muscle relaxants, and other drugs, non-drug treatments, and other NSAIDs, the researchers said.

They looked at 11 studies comparing NSAIDS to placebo in acute low back pain and four in chronic pain.

For acute pain, the studies were heterogeneous, but there was enough information to conclude that NSAIDs were more effective than placebo, with a pooled relative risk for global improvement after one week of 1.19, with a 95% confidence interval from 1.07 to 1.33.

The effect sizes seen in the individual studies were also small, the researchers noted.

Where Does It Hurt? - Health (

Where Does It Hurt?

By Ken Adelman

An NIH doctor talks about advances in pain management and the importance of listening.

Q & A with Dr. Zena Quezado

"Every day, patients tell me they feel genuine pain and suffering," says National Institutes of Health anesthesia specialist Dr. Zena Quezado. "Whether it's psychosomatic or physiologically traceable, I can't tell. But it's true to those for whom it counts most—the patients."

As chief of the department of anesthesia and surgical services at NIH's Clinical Center, Dr. Quezado is proud of advances in pain management.

"We've developed a variety of new drugs and techniques that we use to treat pain. But the best thing that's happened in pain management over the past decade is the attention it's gotten. That's long overdue."

Quezado, 45, was born in Patos, a small city in northeastern Brazil, and grew up in Fortaleza, near the equator. Her father was a civil engineer, and her mother stayed at home with five children.

Quezado received her medical degree from the Federal University of Ceará in her hometown. She moved to the United States in 1986 to intern at Philadelphia's Albert Einstein Medical Center. She stayed there for her residency before moving to NIH's Critical Care Medicine Department in 1990.

She has been an anesthesiologist at Harvard Medical School and Shriners Hospital in Boston and has taught at Harvard and George Washington University medical schools. In 2004 Quezado won an NIH award for excellence in patient care; the next year she won the Director's Award for dedication to the Clinical Center's mission and her leadership of anesthesia services.

Quezado commutes by bicycle between her home near DC's Dupont Circle and the Bethesda campus of NIH. In her office, we discussed what she's learned.

Support Group for Migraine Sufferers on LiveJournal

Fibromyalgia community on LiveJournal

Welcome. This community has been created for people that are suffering and surviving fibromyalgia. All are welcome. That means patients, spouse/significant others, medical professionals, and people wanting to learn more. This is for sharing our daily struggles and pain and good days.

Tuesday, January 22, 2008

BBC NEWS | Health | Gene 'may transform pain relief'

Pain vanished for at least three months in rats who were injected in the spine with a gene that triggers endorphins, the body's natural pain killer.

The therapy did not affect the rest of the nervous system, including the brain, potentially preventing the main side-effects of current pain relief.

Studies suggest drugs do not relieve cancer pain in as many as 66% of cases.

The research appeared in the Proceedings of the National Academy of Sciences.

"Chronic pain patients often do not experience satisfactory pain relief from available treatments due to poor efficacy or intolerable side effects like extreme sleepiness, mental clouding and hallucinations," said Andreas Beutler, part of the team who conducted the study at Mount Sinai School of Medicine in New York.

He said that in some circumstances, patients preferred to continue suffering some pain in order to preserve lucidity.

There is also a potential risk of addiction to opiate drugs.

The team used a disabled cold virus to carry the gene into the spinal fluid of the rats, which had been developed to suffer from chronic pain.

By blocking the pain impulses travelling up to their brains, the rats remained pain-free for at least three months, the researchers wrote.

"Although this research is at a very early stage, the concept of using gene therapy to deliver pain relief is interesting because it could potentially have fewer side effects than conventional pain relief," said Josephine Querido of Cancer Research UK.

But while cancer patients could be among the main beneficiaries of such a technique, a recent European study suggested that as many as 20% of adults suffer from chronic or intermittent pain for which no satisfactory treatment has been found.

Chronic back pain in the UK alone is thought to cost billions.

Scientists have been trying for many years now to harness gene therapy for pain relief but have hit various problems.

This development is "certainly exciting and promising", says Professor Turo Nurmikko, Director of the Pain Research Institute in Liverpool.

"But it is a little too early to say what the ultimate significance of the results is.

"Once the researchers have shown that in animal models of chronic pain, there is long-standing improvement, one could start speaking of a medical breakthrough."

chronic pain anonymous | Google Groups

Chronic Pain Anonymous is a 12 step support group for men and women to share their experience, strength and hope with each other that they may solve their common problem and help others to recover from chronic pain.

Sunday, January 20, 2008

Mind Hacks: An ode to ibuprofen

A lyrical tribute to the pain killer ibuprofen, written by poet Matt Harvey.

The poem was written for BBC Radio 4's Saturday Live, as they had Dr Stewart Adams on the programme discussing his discovery of the drug.

The Telegraph has a great article on its discovery, which includes the fact that he tested the drug on himself to try and shift a troublesome hangover.

I Prefer Ibuprofen

Life is so much easier with effective analgesia

The purpose of pain is to say to the brain:
Ow! Houston we've got a problem…
But once we've got the message we don't need it again and again…

What do we want? Symptom Relief!
When do we want it? Now!

When you've had enough of it there's just no need to suffer it
Just pop a little caplet and Ibuprofen will buffer it

I've had a go with Aspirin, Codeine and Paracetamol
With Solpadeine, Co-codamol, with Anadin and Ultramol
I love them all, I really do, but I prefer Ibuprofen

There are other non-steroidal anti-inflammatory drugs around
Your NSAID's these days are quite thick on the ground
There's Naproxen, there's Nabumetone
and, of course, there's Indomethacin
Each with much to offer us. But I prefer Ibuprofen

I love the way the compound sticks its cheeky little hand in
The way it blocks the enzyme that creates the prostaglandin

Reducing fever, inflammation, and mild to moderate pain

Yes I know it isn't curative, in anyway preventative
But to dwell on what it doesn't do is anally retentative
I know it doesn't treat the cause, the cause will still be there
But it lends a hand, it puts the 'pal' back into palliative care.

It does exactly what you'd expect it to say it would do if it came in a tin

Thursday, January 17, 2008

Disease or Not, the Pain Is Very Real - New York Times

To the Editor:

"Drug Approved. Is Disease Real?" (front page, Jan. 14) does a disservice to your readers, including the millions of patients afflicted by fibromyalgia, a debilitating condition. The fact that Western medicine does not yet understand a condition does not make it any less "real."

Millions of people suffer from the physical pain and crippling fatigue associated with fibromyalgia. We are not hypochondriacs, but sick people in search of a cure, and of more compassionate medical care.

Would that it were true that fibromyalgia patients "obsess over aches that other people simply tolerate"; in truth, they suffer from pain other people can scarcely imagine. To imply, as the article does, that doctors who advocate on behalf of these patients are somehow "in the pocket" of the pharmaceutical industry is to betray a stunning degree of cynicism, and of callow disregard for the real lives and deep suffering of millions of human beings.

Shai Held
New York, Jan. 14, 2008

To the Editor:

The pain of fibromyalgia is real, even if some doctors don't think it is a disease. Fibromyalgia and the related chronic fatigue are syndromes, not discrete diseases. Because there is no single test to identify them does not make them a fiction in the mind of the sufferer.

The pain and discomfort experienced are similar to what ordinary people feel when they have the flu. These are autoimmune disorders, with the exact triggering mechanisms still unknown. There is no cure. Only time and a lower stress lifestyle help.

I am a retired farmer who developed chronic fatigue and fibromyalgia through exposure to grain dust and mold spores. My pain level comes and goes based on my stress level and exposure to airborne proteins and smoke. I have a high pain tolerance, and I take no drugs. When the pain comes, I accept it, and when it goes away, I'm relieved. But it is real.

Fred Schumacher
Mankato, Minn., Jan. 14, 2008

To the Editor:

Your article suggesting that fibromyalgia isn't a disease translates a significant health problem into a polemic. The problem derives from medical materialism. By this I mean that doctors tell patients that nothing's wrong, if no abnormality can be found.

With this stance, patients fall between the cracks of classic medicine left on their own or to the burgeoning alternative medicine industry.

When I took the Hippocratic oath, I didn't pledge to care for only patients with stroke or cancer but instead to do whatever possible to reduce suffering and improve health. Your article will make doctors, relatives and friends of millions with fibromyalgia conclude that their symptoms are just a "physical response to stress, depression, and economic and social anxiety."

This is an opinion ignoring published medical literature showing brain abnormalities in fibromyalgia and drugs that clearly improve patient health.

What's needed is less talk and more federally financed, peer-reviewed research.

Benjamin H. Natelson

Newark, Jan. 15, 2008

The writer, a physician, is a professor of neurosciences and director of the Pain and Fatigue Study Center at U.M.D.N.J.-New Jersey Medical School.

Chronic-pain treatment without side effects : Nature News

A common class of drug could be targeted to give better pain relief.

A drug has been found that treats chronic pain in mice, without the usual painkiller side effects of sedation, addiction or developing tolerance.

Whether the compound has the same effect in people remains to be seen, but researchers are approaching the drug's target with "cautious optimism".

The compound comes from a well-known class of drugs, the benzodiazepines, that are widely used for sedation or to treat anxiety. Benzodiazepines act on brain pathways involved with pain perception, but have not been very effective at relieving pain. A team led by Hanns Ulrich Zeilhofer of the University of Zurich in Switzerland wanted to know why.

They first tested diazepam — commonly known as valium — by injecting it into the spines of mice. The spine is one of the body's direct pain highways, so blocking pain signals here might help avoid side effects that turn up when a drug hits the brain. In this system the researchers found that diazepam could indeed relieve pain — mice that either endured a painful injection or had a nerve squeezed to simulate chronic pain were less bothered if they received the spinal injections.

Receptive strategy

Researchers know that valium acts on a receptor called γ-aminobutyric acid, or GABA, in the spine, and that GABA has different parts or subunits that might be responsible for the different effects of the drug. To investigate, the team looked at four types of mutant mouse, each of which had a different subunit of this GABA receptor rendered inactive, to see what valium would do.

They found that two of the subunits, α2 and α3, had to be present for the drug to relieve pain. Thankfully it is a different subunit, α1, that causes sleepiness when the drugs hit the brain. The researchers report their results in Nature 1.

"What we have shown is which receptors need to be targeted," says Zeilhofer. Being able to zoom in on the target like this is what’s most exciting about this work, says Clifford Woolf, an anaesthesiologist at Massachusetts General Hospital in Charlestown.

Drug development

If giving drugs via the spine was practical in humans, the team could just use benzodiazepines in this way to relieve pain without side effects. But this requires a catheter and is not suitable for most patients.

So knowing which parts of GABA to aim for, the team tested the effects of a benzodiazepine known not to act on the α1 sleep-inducing bit of the GABA receptor: a compound memorably named L-838,417. They gave the compound orally to rats and it worked to relieve pain without sedating them like other painkillers. Moreover, it didn’t lose its effect when treatment continued for a few days. This issue of tolerance is a problem for drugs such as morphine.

Additionally they imaged the rats’ brains with functional magnetic resonance imaging to see what effect L-838,417 was having on pain-processing areas. As expected, the drug reduced activity in brain areas related to pain, as well as in areas known to be involved in the emotional distress that comes with hurt.

The next step is to find drugs that will act the same way in humans. Some α1-sparing benzodiazapines are already being developed for the treatment of anxiety without sleepy side effects. But the α2 and α3 might not be the same in people as in rodents.

Woolf is adopting an attitude of "cautious optimism" towards these results. "It’s always a long way between pre-clinical studies and proof-of-concept in man," he says.

Wednesday, January 16, 2008

BBC NEWS | Health | Clue to migraine headache cause

Clue to migraine headache cause

Scientists may be a step closer to uncovering the cause of certain types of debilitating migraine headaches.

A French team observed activation in the hypothalamus region of the brain as sufferers had a migraine attack.

The hypothalamus has long been suspected as it regulates physiological responses to factors known to trigger headaches, such as hunger.

It is hoped the discovery, featured in the journal Headache, could lead to new treatments.

The researchers, from Rangueil Hospital, used a technique called Positron Emission Tomography (PET), which contrasts functional activity within the brain, on seven patients with migraine without aura, the most common type of migraine.

Previously, activation in the brain stem and midbrain, and a thickening in some areas of the cortex were seen in migraine sufferers.

The present study may have seen a more detailed pathogenesis of the condition for two reasons.

First, timing was crucial: to capture an attack as it happened, patients rushed to hospital without self-medicating, arriving on average around three hours after the onset of the migraine.

Second, the observed headaches were spontaneous, and not chemically induced as in other laboratory studies.

Lead researcher Dr Marie Denuelle said: "When you induce the attack you miss the hypothalamic activation.

"We suspect the hypothalamus may play a role in the start of the migraine attack.

"But to prove it we would need to do similar study before the start of an attack."

Dr Andrew Dowson, director of headache services at Kings College Hospital, London, said: "It has been suggested for many years that the hypothalamus is involved in the early stages of migraine attacks.

"But there are other factors involved in the early generation of headache."

Suicide headaches

Activation of the hypothalamus had previously only been seen in cluster headache, a different and altogether more crippling condition.

Cluster headache sufferers experience headaches on a regular basis: for certain months of the year in the episodic form, or every day at regular intervals in the chronic form.

So debilitating can the attacks be that they have been dubbed "suicide headaches" because some sufferers have taken their own lives.

The new evidence for hypothalamic activation in migraine may explain why some migraine drugs, particularly the triptans, can sometimes be effective at aborting a cluster headache attack.

However, Professor Peter Goadsby, of the Insitute of Neurology at University College London, said there were distinct clinical and physiological differences between cluster headache and migraine.

He said: "The area [of the hypothalamus] reported as activated in migraine is about 10mm more anterior than the cluster headache area.

"The hypothalamus is not one thing but a collection of discrete neurons."

Professor Goadsby said a cascade of changes in the brain seemed to cause the migraine problem.

"It's easy to think that migraine is a specific brain disorder, but it is a series of systems that go wrong - a system disorder.

"There is no single holy grail. Multiple structures are involved."

Pain Treatment Advocacy - The National Foundation for the Treatment of Pain

Suffering Chronic Pain

Voices of People with Pain

Pain Relief Network

Welcome to PRN. We are a network of pain patients, family members of people in pain, physicians, attorneys, and activists who are working toward a day when people in pain will be afforded the simple dignity and compassion due all ill Americans.

On July 12, 2007 Siobhan Reynolds, the president and founder of PRN, herself the family member of a now deceased chronic pain patient, and John Flannery, one of the private attorneys with whom PRN had worked on several cases in the past, testified before the House Subcommittee on Crime (Read Testimony). The hearing was covered by John Tierney in his blog on the New York Times website and much was accomplished to put the documentary proof of this government sponsored holocaust on the Congressional Record.

As a result, we are working with several members of the Subcommittee to introduce legislation to return the regulation of medicine to the Fifty States where, according to the US Supreme Court, it rightfully belongs.

We are also working to educate the media and members of Congress as to the severity of the problem should political will somehow magically develop out of the swirling chaos that now characterizes Capitol Hill, informing members and their staff of the substantive press coverage PRN developed on our issue (When Is a Pain Doctor a Drug Pusher?) and the damage being done to their constituents.


Pain and the Law: Developed by St. Louis University and the American Society of Law, Medicine and Ethics under a grant from the May Day Fund

This site focuses primarily on the legal issues involving pain management and palliative care.

Tuesday, January 15, 2008

Medical News: Sickle Cell Pain More Pervasive than Generally Recognized

Sickle Cell Pain More Pervasive than Generally Recognized

By Charles Bankhead, Staff Writer, MedPage Today

RICHMOND, Va., Jan. 14 -- Patients with sickle cell disease endure pain that is more frequent and more severe than commonly appreciated by clinicians, investigators here found.

In a study of 232 patients ages 16 and older, recruited throughout Virginia, more than half the patients reported having pain more than half the time, Wally R. Smith, M.D., of Virginia Commonwealth University, and colleagues reported in the Jan. 15 issue of Annals of Internal Medicine.

Almost 30% of the patients said they were in pain virtually every day, the survey found.

Yet most pain days did not correlate with sickle cell crises or health care utilization, a traditional proxy for pain and underlying vascular occlusion.

"Our findings suggest a vast, mostly submerged iceberg of sickle cell
pain that is not seen by most professionals, but rather is managed
outside of medical facilities," the authors stated. "The extremely
low proportion of sickle cell disease pain that is managed within
medical facilities explains why treating physicians might believe
that sickle cell pain is the exception rather than the rule."

Patients with sickle cell disease may have severe and disabling pain
that typically occurs in the long bones, joints, back, abdomen, and
chest, the authors said. Vaso-occlusive pain accounts for most
medical contacts with sickle cell patients. The frequently episodic
nature of contacts may lead to the conclusion that patients do not
have pain on most days.

Caregivers traditionally have used the term "crisis" to describe
sickle cell patients' medical contacts and have used the term chronic
pain syndrome to describe pain associated with sickle cell disease
complications, such as ankle ulcers or avascular necrosis. However,
the relationship among sickle disease pain, crises, and health care
utilization had not been examined in a large-scale longitudinal
epidemiologic study, according to the authors.

In the Pain in Sickle Cell Epidemiology Study (PiSCES), patients
completed daily diaries for as long as six months, recording maximum
pain (on a scale of 0-9), crises, and use of hospital, emergency, or
unscheduled ambulatory care for pain.

Overall, 54.5% of patients reported pain on more than half (³51%) of 31,017 patient-days. On 38.3% of days, patients described their pain as being at less than crisis level and not requiring unplanned health care utilization. They reported crisis-level pain on 12.7% of days, but managed the pain at home. The patients reported unplanned health care utilization on 3.5% of days. Inclusion of scheduled visits increased utilization to only 5.1% of days.

The investigators found that 29.3% of participants reported having pain on more than 95% of diary days, whereas 14.2% reported pain on no more than 5% of diary days.

Home opiate use independently predicted pain, crises, and utilization. Mean pain intensity increased with the percentage of pain days (P<0.001). Pain intensity was significantly higher on health care utilization days (P<0.001) but did not predict crisis episodes.

"Pain in adults with sickle cell disease is the rule rather than the exception and is far more prevalent and severe than previous large-scale studies have portrayed," the authors concluded. "It is mostly managed at home; therefore, its prevalence is probably underestimated by health care providers, resulting in misclassification, distorted communication, and undertreatment."

Drug Approved. Is Disease Real? - New York Times

Drug Approved. Is Disease Real?

Fibromyalgia is a real disease. Or so says Pfizer in a new television advertising campaign for Lyrica, the first medicine approved to treat the pain condition, whose very existence is questioned by some doctors.

For patient advocacy groups and doctors who specialize in fibromyalgia, the Lyrica approval is a milestone. They say they hope Lyrica and two other drugs that may be approved this year will legitimize fibromyalgia, just as Prozac brought depression into the mainstream.

But other doctors — including the one who wrote the 1990 paper that defined fibromyalgia but who has since changed his mind — say that the disease does not exist and that Lyrica and the other drugs will be taken by millions of people who do not need them.

As diagnosed, fibromyalgia primarily affects middle-aged women and is characterized by chronic, widespread pain of unknown origin. Many of its sufferers are afflicted by other similarly nebulous conditions, like irritable bowel syndrome.

Because fibromyalgia patients typically do not respond to conventional painkillers like aspirin, drug makers are focusing on medicines like Lyrica that affect the brain and the perception of pain.

Advocacy groups and doctors who treat fibromyalgia estimate that 2 to 4 percent of adult Americans, as many as 10 million people, suffer from the disorder.

Those figures are sharply disputed by those doctors who do not consider fibromyalgia a medically recognizable illness and who say that diagnosing the condition actually worsens suffering by causing patients to obsess over aches that other people simply tolerate. Further, they warn that Lyrica's side effects, which include severe weight gain, dizziness and edema, are very real, even if fibromyalgia is not.

Despite the controversy, the American College of Rheumatology, the Food and Drug Administration and insurers recognize fibromyalgia as a diagnosable disease. And drug companies are aggressively pursuing fibromyalgia treatments, seeing the potential for a major new market.

Hoping to follow Pfizer's lead, two other big drug companies, Eli Lilly and Forest Laboratories, have asked the F.D.A. to let them market drugs for fibromyalgia. Approval for both is likely later this year, analysts say.

Worldwide sales of Lyrica, which is also used to treat diabetic nerve pain and seizures and which received F.D.A. approval in June for fibromyalgia, reached $1.8 billion in 2007, up 50 percent from 2006. Analysts predict sales will rise an additional 30 percent this year, helped by consumer advertising.

In November, Pfizer began a television ad campaign for Lyrica that features a middle-aged woman who appears to be reading from her diary. "Today I struggled with my fibromyalgia; I had pain all over," she says, before turning to the camera and adding, "Fibromyalgia is a real, widespread pain condition."

Doctors who specialize in treating fibromyalgia say that the disorder is undertreated and that its sufferers have been stigmatized as chronic complainers. The new drugs will encourage doctors to treat fibromyalgia patients, said Dr. Dan Clauw, a professor of medicine at the University of Michigan who has consulted with Pfizer, Lilly and Forest.

"What's going to happen with fibromyalgia is going to be the exact thing that happened to depression with Prozac," Dr. Clauw said. "These are legitimate problems that need treatments."

Dr. Clauw said that brain scans of people who have fibromyalgia reveal differences in the way they process pain, although the doctors acknowledge that they cannot determine who will report having fibromyalgia by looking at a scan.

Lynne Matallana, president of the National Fibromyalgia Association, a patients' advocacy group that receives some of its financing from drug companies, said the new drugs would help people accept the existence of fibromyalgia. "The day that the F.D.A. approved a drug and we had a public service announcement, my pain became real to people," Ms. Matallana said.

Ms. Matallana said she had suffered from fibromyalgia since 1993. At one point, the pain kept her bedridden for two years, she said. Today she still has pain, but a mix of drug and nondrug treatments — as well as support from her family and her desire to run the National Fibromyalgia Association — has enabled her to improve her health, she said. She declined to say whether she takes Lyrica.

"I just got to a point where I felt, I have pain but I'm going to have to figure out how to live with it," she said. "I absolutely still have fibromyalgia."

But doctors who are skeptical of fibromyalgia say vague complaints of chronic pain do not add up to a disease. No biological tests exist to diagnose fibromyalgia, and the condition cannot be linked to any environmental or biological causes.

The diagnosis of fibromyalgia itself worsens the condition by encouraging people to think of themselves as sick and catalog their pain, said Dr. Nortin Hadler, a rheumatologist and professor of medicine at the University of North Carolina who has written extensively about fibromyalgia.

"These people live under a cloud," he said. "And the more they seem to be around the medical establishment, the sicker they get."

Dr. Frederick Wolfe, the director of the National Databank for Rheumatic Diseases and the lead author of the 1990 paper that first defined the diagnostic guidelines for fibromyalgia, says he has become cynical and discouraged about the diagnosis. He now considers the condition a physical response to stress, depression, and economic and social anxiety.

"Some of us in those days thought that we had actually identified a disease, which this clearly is not," Dr. Wolfe said. "To make people ill, to give them an illness, was the wrong thing."

In general, fibromyalgia patients complain not just of chronic pain but of many other symptoms, Dr. Wolfe said. A survey of 2,500 fibromyalgia patients published in 2007 by the National Fibromyalgia Association indicated that 63 percent reported suffering from back pain, 40 percent from chronic fatigue syndrome, and 30 percent from ringing in the ears, among other conditions. Many also reported that fibromyalgia interfered with their daily lives, with activities like walking or climbing stairs.

Most people "manage to get through life with some vicissitudes, but we adapt," said Dr. George Ehrlich, a rheumatologist and an adjunct professor at the University of Pennsylvania. "People with fibromyalgia do not adapt."

Both sides agree that people who are identified as having fibromyalgia do not get much relief from traditional pain medicines, whether anti-inflammatory drugs like ibuprofen — sold as Advil, among other brands — or prescription opiates like Vicodin. So drug companies have sought other ways to reduce pain.

Pfizer's Lyrica, known generically as pregabalin, binds to receptors in the brain and spinal cord and seems to reduce activity in the central nervous system.

Exactly why and how Lyrica reduces pain is unclear. In clinical trials, patients taking the drug reported that their pain — whether from fibromyalgia, shingles or diabetic nerve damage — fell on average about 2 points on a 10-point scale, compared with 1 point for patients taking a placebo. About 30 percent of patients said their pain fell by at least half, compared with 15 percent taking placebos.

The F.D.A. reviewers who initially examined Pfizer's application for Lyrica in 2004 for diabetic nerve pain found those results unimpressive, especially in comparison to Lyrica's side effects. The reviewers recommended against approving the drug, citing its side effects.

In many patients, Lyrica causes weight gain and edema, or swelling, as well as dizziness and sleepiness. In 12-week trials, 9 percent of patients saw their weight rise more than 7 percent, and the weight gain appeared to continue over time. The potential for weight gain is a special concern because many fibromyalgia patients are already overweight: the average fibromyalgia patient in the 2007 survey reported weighing 180 pounds and standing 5 feet 4 inches.

But senior F.D.A. officials overruled the initial reviewers, noting that severe pain can be incapacitating. "While pregabalin does present a number of concerns related to its potential for toxicity, the overall risk-to-benefit ratio supports the approval of this product," Dr. Bob Rappaport, the director of the F.D.A. division reviewing the drug, wrote in June 2004.

Pfizer began selling Lyrica in the United States in 2005. The next year the company asked for F.D.A. approval to market the drug as a fibromyalgia treatment. The F.D.A. granted that request in June 2007.

Pfizer has steadily ramped up consumer advertising of Lyrica. During the first nine months of 2007, it spent $46 million on ads, compared with $33 million in 2006, according to TNS Media Intelligence.

Dr. Steve Romano, a psychiatrist and a Pfizer vice president who oversees Lyrica, says the company expects that Lyrica will be prescribed for fibromyalgia both by specialists like neurologists and by primary care doctors. As doctors see that the drug helps control pain, they will be more willing to use it, he said.

"When you help physicians to recognize the condition and you give them treatments that are well tolerated, you overcome their reluctance," he said.

Both the Lilly and Forest drugs being proposed for fibromyalgia were originally developed as antidepressants, and both work by increasing levels of serotonin and norepinephrine, brain transmitters that affect mood. The Lilly drug, Cymbalta, is already available in the United States, while the Forest drug, milnacipran, is sold in many countries, though not the United States.

Dr. Amy Chappell, a medical fellow at Lilly, said that even though Cymbalta is an antidepressant, its effects on fibromyalgia pain are independent of its antidepressant effects. In clinical trials, she said, even fibromyalgia patients who are not depressed report relief from their pain on Cymbalta.

The overall efficacy of Cymbalta and milnacipran is similar to that of Lyrica. Analysts and the companies expect that the drugs will probably be used together.

"There's definitely room for several drugs," Dr. Chappell said.

But physicians who are opposed to the fibromyalgia diagnosis say the new drugs will probably do little for patients. Over time, fibromyalgia patients tend to cycle among many different painkillers, sleep medicines and antidepressants, using each for a while until its benefit fades, Dr. Wolfe said.

"The fundamental problem is that the improvement that you see, which is not really great in clinical trials, is not maintained," Dr. Wolfe said.

Still, Dr. Wolfe expects the drugs will be widely used. The companies, he said, are "going to make a fortune."