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FMS Community Newsletter #94
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~The best new pain cures, with a focus on women
~More drugs hobble restless legs syndrome
~Some pin hopes on study of functional syndromes
~Fibromyalgia patients show an abnormal dopamine response to pain.
~Randomized controlled study of the antinociceptive effect of ultrasound on trigger point therapy?
~Gene cluster linked to chronic fatigue
~FDA issues new safety rules for vitamins

The best new pain cures, with a focus on women

Story Highlights
? Until recently, most pain research didn't consider women's hormones, physique
? Researchers finding "dramatic" gender differences in experiencing pain
? Today prevention, early intervention viewed as "absolutely critical"
? Women also more prone to conditions involving the immune system

By Melanie Haiken
You've got achy shoulders from carrying the kids, the groceries, or your incredibly heavy handbag. You look for the right pill to pop, but what should you take? Aspirin? Ibuprofen? Or, you're about to get your period. You know you'll get killer cramps or that nasty headache any minute now, but nothing you take seems to help once the pain hits.

You're not alone: Many women have a tough time finding the right kind of relief for their pain --and for good reason: Until recently, experts hadn't actually studied women's pain specifically, and most research wasn't conducted with a woman's hormones and physique in mind. All that's changing, though.

Docs now know that to banish our aches, they must develop treatments formulated for women's bodies. What's more, researchers are also looking for -- and finding -- ways to head pain off at the pass, so those of us with chronic troubles such as migraine, fibromyalgia, or backache don't have to be hobbled by pain on a daily basis. Here, how the new research will help you live an (almost) pain-free life. ( Smart ways to banish pain )

The prevention revolution

"The old way of dealing with pain was to 'wait until it hurts enough to treat it,'" says Carol A. Foster, M.D., director of Valley Neurological Headache and Research Center in Phoenix, Arizona, and author of "Migraine: Your Questions Answered." "But in the last few years, there has been a complete turnaround. Now we know that prevention and early intervention are absolutely critical."

The new thinking has made all the difference for Carolyn Robbins of Petaluma, California, who suffers from chronic back and neck pain, the result of a spinal-disk injury combined with nerve damage from Guillain-Barre syndrome. "If you've ever had an exposed nerve in your tooth, you know what it feels like," says Robbins, who describes her pain as "electrical shocks" in her upper and lower back.

The 45-year-old mother of two doesn't wait until pain hits her full force before treating it. She now relies on a daily prevention regimen, starting with a hot shower and a double dose of ibuprofen. She swims two to three times a week for strength and mobility, and gets weekly massage and chiropractic treatments. And during those times when things get really bad, she pulls out the stronger painkillers prescribed by her doctor. "I've found that it's not a good idea to try to power through the pain, because other things start to go wrong," Robbins says. "Pain depletes your system as much as exposure to germs."

Just five years ago, a "kitchen sink" approach like Robbins' might have been pooh-poohed by pain-management types, who would have been quick to prescribe hard-core, addictive drugs such as oxycontin for such a serious condition. But now the focus has switched. "It used to be, people treated the pain and didn't always treat the underlying disease," Foster says.

The problem with such an approach, though, is that it sets up a vicious cycle of dependence. "Giving narcotic pain pills to headache patients is like giving cookies to diabetics," she adds.

So how do you break the habit of heading straight for the medicine cabinet? No matter what your source of pain, the first step is to get an accurate diagnosis and then set up an early intervention strategy with your doctor, says Neil Kirschen, M.D., president of the American Association of Orthopedic Medicine and chief of pain management at South Nassau Community Hospital in New York. "The whole goal of pain management today is to keep pain from becoming chronic," he says.

The reason? Pain actually causes the brain to fire off a stress response that, over time, makes nerves more and more sensitive -- and thus better able to telegraph intense pain to you. In other words, pain actually begets pain.

Nan Weiner, executive editor at San Francisco magazine, is a case in point. When she broke her ankle eight years ago, it never completely healed, and the pain became chronic. What should have been a relatively simple injury became an odyssey that had Weiner visiting specialists all over San Francisco. She finally found a podiatrist who "took a detective-like approach to the problem," Weiner says, by exploring and treating each joint and tendon in a methodical search for the pain's source. Thanks to this care, which includes regular pain-preventing cortisone shots, the 55-year-old mother of one has been able to resume her hobby of salsa dancing.

Zooming in on female pain

We know that men don't suffer menstrual pain, but that's not the only fun they're missing. "Research is uncovering very dramatic differences in how the genders experience pain," says Mark Allen Young, a professor at New York College of Podiatric Medicine and author of "Women and Pain: Why It Hurts and What You Can Do."

It all starts with hormones. There is no getting around how profoundly hormones such as estrogen and testosterone affect the central nervous system, which is responsible for perceiving and transmitting the sensation of pain. According to experts, this is one reason why conditions such as osteoarthritis, headaches, and irritable bowel syndrome strike women at much higher rates than men.

Our physical differences really matter, too. "We've only recently begun to grasp that women's body architecture is completely different from men's," Young says. Because women walk differently, for instance, they put pressure on joints, muscles, and bones in very different ways than men do. "Starting with the knees and hips and working up to the shoulders, spine, and neck, how a person walks can have a huge impact on how pain develops later in life," Young says. Just last year, one medical-implant maker finally recognized this fact by creating a knee implant just for women.

Women are also more prone to conditions involving the immune system, says Deborah Metzger, M.D., an OB-GYN and specialist in integrative pain management in Los Altos, California. Scientists have long known that women have stronger immune systems than men, she says. That strength can backfire, though, leading women to suffer from far more autoimmune disorders -- in which the immune system attacks itself -- and the host of mysterious diseases thought to sometimes result from an overreactive immune system, such as celiac disease, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, and many types of pelvic pain.

"Women tend to have hyperalert immune systems, which is good," Metzger says. "But once the immune system gets stirred up, it can turn into a feeding frenzy." The fired-up immune activity produces inflammatory chem?icals that fuel all types of muscle and joint pain; it can also activate nerves in vulnerable spots like the lower back (sciatica), the head (migraines), and the pelvis (endometriosis and pelvic pain).

New relief for headaches

There's good news for women who suffer migraines -- and most other types of headaches -- which they do at twice the rate of men. Headaches are one area where the new focus on prevention can be seen in a host of treatment options, including Botox. Considered experimental just a few years ago, Botox injections (in which the botulinum toxin type A is used to paralyze specific muscles in the forehead, brow, temples, and neck) is now offered by many hospital pain clinics. Botox is also extremely effective for certain types of neck pain, such as cervical dystonia.

Another treatment that's crossing over from fringy "alternative" practitioners to mainstream pain clinics is neuromodulation, a.k.a. transcutaneous electrical nerve stimulation, or TENS. "Think of TENS as acupuncture without needles that you can wear at home," says Joseph Shurman, M.D., pioneer of a new pain-management model at Scripps Memorial Hospital in La Jolla, California, and chairman of pain management. (Take that! (for pain) )

Extremely effective for neck pain, back pain, and some kinds of headaches, the treatment involves applying electrodes to the skin to stimulate particular nerves. "Neuromodulation works by trying to change the pain message into something else," Kirschen says.

Acupuncture is also a routine part of treatment in many headache clinics; it's used in conjunction with pain medication and other treatments. Women seem to respond particularly well to this therapy, Young says. "There are certain acupuncture points that are better for women than for men," he adds.

Fighting the fatigue

In the past year, some of the biggest headlines in pain management have been about fibromyalgia (chronic bodywide pain in joints, muscles, and tendons) and CFS, two conditions that strike women at as much as six times the rate of men. After years of failing to take these conditions seriously, the Centers for Disease Control and Prevention and other groups have recently mounted aggressive public-information campaigns alerting women to the prevalence of these conditions and the importance of accurate diagnosis and treatment. Experts have also made dramatic gains in finding treatments that work by focusing on the sleep problems and physical weakness that seem to fuel these diseases. (Could painkillers be hurting your heart? )

Marly Silverman of Pompano Beach, Florida, learned she had fibromyalgia and CFS more than 10 years ago. "It felt like acid chemicals going through my veins," she says, describing the excruciating pain that forced her to quit her job as vice president of a bank after fruitlessly seeking treatment from a variety of specialists. Today, Silverman manages her pain with a plethora of remedies, including painkillers, anti?spasmodics (muscle relaxants), and lidocaine patches for localized pain. To speed research into these complex and mysterious illnesses, Silverman founded PANDORA, a patient advocacy and research organization that cosponsors a national conference on the latest research into these and related neuro-endocrine immune conditions.

In studying other immune-triggered conditions such as Crohn's disease -- which also affects women at two to six times the rate of men -- experts have made a similar breakthrough. Instead of treating digestive symptoms such as gas, diarrhea, and constipation (common in Crohn's and IBS), experts realized the culprit might be an underlying food sensitivity, most likely to wheat gluten, milk protein, or one of several other common allergens. What happens, integrative pain specialist Deborah Metzger says, is that an overreactive immune system protests against the irritating foods, causing systemic inflammation throughout the body. She says that in recent years she's had great success by putting patients on the Sugar Busters diet, which eliminates sugar, white flour, and other suspect foods. Metzger's advice: Find a doctor who will analyze all aspects of your lifestyle rather than just medicate pain symptoms.

How to be a good pain patient

There's no question that women aren't always taken seriously when they ask for help with a condition that doesn't have a clear-cut explanation. Just ask those with pelvic pain. Chronic pain is bad enough, but pain down there can be very difficult to describe. "I see so many patients who come in with pelvic, vulvar, ovarian, and/or lower-back pain that they've been dealing with for years, but they can't even tell exactly where the pain is coming from," Metzger says. "There are certain nerves on the abdominal wall that tend to be vulnerable spots. It takes time and patience to pinpoint what's really going on."

That's what happened to Jo Ziegler, 39, of Katonah, New York. She struggled for more than a year with lower- abdominal pain. And it wasn't until after trying a wheat- and sugar-free diet and having a colonoscopy that she visited a surgeon who made a correct hernia diagnosis. One simple outpatient procedure, and Ziegler was rid of the pain.

Often, the biggest treatment barriers women encounter are plain old stereotypes: Women are perceived as "emotional" when they try to talk about what's bothering them, says Joseph Shurman, M.D., whose wife, Gloria Shurman, Ph.D., suffers from chronic pain. "But how can you not get emotional if it hurts, and it seems like nobody will listen?" Gloria says.

The solution is to take a proactive approach, the Shurmans say, even if you need to look in the mirror and give yourself a pep talk and write down a list of symptoms or questions before you head for the doctor's office. "The most important thing is to be persistent," Gloria Shurman says. "If you're in pain, don't ever take no for an answer."


Some pin hopes on study of functional syndromes Tina Hesman Saey St. Louis Post-Dispatch

All Tina Allen wants is a doctor like TV?s Dr. House. He?d figure out what?s wrong with her.

She has plenty of symptoms and diagnoses. Her medical records cram a tote bag 6 inches thick. She?s boiled down the highlights for new doctors into a four-page summary. It starts with a list of 29 symptoms and 26 diagnoses and ends with a plea for a House-like commitment to get to the bottom of what?s wrong.

Allen has a suite of conditions that includes irritable bowel syndrome, fibromyalgia, headaches, and pain and tingling in her hands and arms.

Millions of people across the country share at least one of Allen?s conditions, and many battle more than one.

Doctors have been stumped as to why those people are so susceptible.

But researchers now think the ailments may have a common cause. Studies have shown that the brains of people with these conditions may interpret pain signals differently than those of other people.

Doctors have labeled the problems ?functional syndromes? because they haven?t found a physical cause for the complaints.

In fact, most patients with combinations of these conditions have been told at least once that the problem is all in their heads.

?The way that society and the health-care system responds to these disturbances is part of the problem,? said Dr. Emeran Mayer, director of neurovisceral sciences and women?s health at the University of California at Los Angeles.

Most of the time patients are referred to specialists and subspecialists to deal with individual sets of symptoms. Patients tend to talk about digestive problems only with their gastroenterologists, saving joint pain, headaches and other problems for other specialists, Mayer said.

But patients will report those other problems if asked.

About eight years ago, Dr. Ray Clouse, a gastroenterologist at Washington University, and his colleagues started asking patients to fill out a form listing about 30 symptoms, only a subset of which included stomach and bowel problems. Patients who had conditions such as Crohn?s disease or ulcers usually would mark only stomach pain and bleeding. But patients with irritable bowel syndrome and related conditions often would tick off nearly all the digestive tract symptoms plus a host of others including trouble sleeping, joint and muscle pain, lower back pain and headaches, Clouse said.

As many as one in five people have irritable bowel syndrome. Between 3 million and 6 million people, most of them women, suffer from fibromyalgia. People with fibromyalgia experience joint and muscle pain, fatigue and multiple tender spots. The tingling and pain in Allen?s hands, a condition known as peripheral neuropathy, affects about 20 million people. About half of patients with one of the ailments also have others, such as chronic fatigue syndrome, tension headaches, restless leg syndrome or multiple chemical sensitivity.

The doctors weren?t the first to note that patients with functional syndromes often have a history of psychiatric conditions such as depression or anxiety.

?That was a big distraction,? Clouse said.

The correlation pushed doctors into two camps: those who believed the syndromes were psychiatric conditions and those who thought they had physical causes. The fact that low doses of antidepressants or talk therapy are often effective in treating irritable bowel syndrome and other functional disorders further complicates the matter, Clouse said.

Brain imaging studies show that the nerves of people with functional syndromes send normal pain signals to the brain. Once those signals reach the brain, though, they are processed in areas involved in emotion, stress and thinking. That processing center appears to be more active in people with functional disorders, suggesting that the interpretation of pain signals, rather than the sensation itself, goes awry in people with the syndromes, Clouse said.

What?s more, the geared-up processing center may rile up the autonomic nervous system, the part of the nervous system that controls automatic responses such as sweating, heartbeat and blood pressure, so it makes the person sweat, causes cramps and triggers pain. Those sensations are sent back to the brain where the whole process repeats, each time racheting up the patient?s pain and distress, Clouse said.

Clouse and his colleague Dr. Gregory Sayuk, a Washington University gastroenterologist who specializes in irritable bowel syndrome and other functional digestive syndromes, are trying to understand how pain is processed in people with multiple functional syndromes. They have already shown that the pain processing center is more active in people with irritable bowel syndrome than in people without it.

Now they will look at how people like Tina Allen, with many functional syndromes, process pain compared with people who have only irritable bowel syndrome and with people who have no syndromes.

Allen, who is 50, made the trip from her home in Kansas City to participate in the study.

?I have believed my whole life that there?s some sort of interference between my GI tract and my brain,? she said. Her test results tell her she?s not crazy. ?I have quantifiable evidence of physical processes, so it?s not just psychosomatic.?

Mayer predicts that within five years scientists will finally understand what drives functional syndromes. Finding treatments will probably take longer, but at least Allen and others may finally know what is wrong with them.


Fibromyalgia patients show an abnormal dopamine response to pain.

Eur J Neurosci. 2007 Jun;25(12):3576-82.

Wood PB, Schweinhardt P, Jaeger E, Dagher A, Hakyemez H, Rabiner EA, Bushnell MC, Chizh BA.
McGill University Centre for Research on Pain, Faculty of Dentistry, 3640 University Street, Strathcona Building, Montreal, QC, Canada, H3A 2B2.

Fibromyalgia is characterized by chronic widespread pain and bodily tenderness and is often accompanied by affective disturbances. Accumulating evidence indicates that fibromyalgia may involve a dysfunction of modulatory systems in the brain.

While brain dopamine is best known for its role in pleasure, motivation and motor control, recent evidence suggests that it is also involved in pain modulation. Because dopamine is implicated in both pain modulation and affective processing, we hypothesized that fibromyalgia may involve a disturbance of dopaminergic

Fibromyalgia patients and matched healthy control subjects were subjected to deep muscle pain produced by injection of hypertonic saline into the anterior tibialis muscle. In order to determine the endogenous release of dopamine in response to painful stimulation, we used positron emission tomography to examine binding of [(11)C]-raclopride (D2/D3 ligand) in the brain during injection of painful hypertonic saline and nonpainful normal saline.

Fibromyalgia patients experienced the hypertonic saline as more painful than healthy control subjects. Control subjects released dopamine in the basal ganglia during the painful stimulation, whereas fibromyalgia patients did not. In control subjects, the amount of dopamine release correlated with the amount of perceived pain but in fibromyalgia patients no such correlation was observed.

These findings provide the first direct evidence that fibromyalgia patients have an abnormal dopamine response to pain. The disrupted dopaminergic reactivity in fibromyalgia patients could be a critical factor underlying the widespread.


Randomized controlled study of the antinociceptive effect of ultrasound on trigger point therapy?

Clin Rehabil. 2007 May;21(5):411-7. Srbely JZ, Dickey JP. Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.

OBJECTIVE: To investigate whether therapeutic ultrasound modulates the pain sensitivity of myofascial trigger points.

DESIGN: Repeated measures, single-blinded randomized controlled trial of ultrasound treatment of trigger points.

SETTING: Outpatient injury rehabilitation clinic. SUBJECTS : Forty-four patients (22 males, 22 females) with trigger points identified within the trapezius muscle.

INTERVENTIONS: Five-minute therapeutic intensity of ultrasound versus 5-min low-intensity application of ultrasound to a trapezius myofascial trigger point locus.

MAIN MEASURES: Pain pressure threshold readings were measured at the trapezius trigger point site before and after exposure to the ultrasound intervention.

RESULTS: Pain pressure threshold scores increased an average of 44.4 (14.2)% after therapeutic exposure to ultrasound (pre-ultrasound test 35.4 (8.5) N, post-ultrasound test 51.1 (12.8) N). No significant
difference in pain pressure threshold scores was observed with low-intensity ultrasound exposures (pre-ultrasound 36.1 (6.1) N, post-ultrasound 36.6 (4.8) N).

CONCLUSIONS : Therapeutic exposures to ultrasound reduce short-term trigger point sensitivity. Ultrasound may be a useful clinical tool for the treatment and management of trigger points and myofascial
pain syndromes.


Gene cluster linked to chronic fatigue

Australian researchers have identified a cluster of genes linked to chronic fatigue syndrome which may help finally explain the mysterious condition.

The team from the University of NSW sifted through more than six million pieces of DNA information in people who had glandular fever, including half who went on to develop chronic fatigue.

Their goal was to identify which genes appeared to be more active in the people who went on to get fatigue, to shed light on what triggers the unexplained condition.

Professor Andrew Lloyd and his colleagues at the Centre for Infection and Inflammation Research were able to find 35 genes linked to the symptoms of the illness. 'These (35) genes might point to the nature
of the disease process that underlies chronic fatigue syndrome, which is currently unknown,' said Prof Lloyd, whose findings are published in the latest Journal of Infectious Diseases.

Chronic fatigue is most commonly triggered by an acute illness, like glandular fever. It is characterised by extreme tiredness but recent studies have left researchers puzzled as to what it actually is.

'We know it's not a psychiatric disorder, and doesn't appear to have anything to do with immune responses or hormones or the severity of the virus,' Prof Lloyd said. 'So that's left us thinking it's some kind of brain disorder.'

The team decided to analyse brain patterns by studying blood samples of 15 people with glandular fever, including some who also developed fatigue. The work was part of a larger project tracking the long-term
health of people infected by three infections - the mosquito borne Ross River virus, Q fever bacterial infection and Epstein-Barr virus, which causes glandular fever - in the central NSW city of Dubbo.

Prof Lloyd said the findings were the tentative beginnings of better understanding the disease. 'It's given us the starting point for some gene expression pattern that might become a diagnostic test for the condition,' he said. 'And it's given some clues of what the disease
process might be that underlies the disorder.' (c) 2007 AAP


~FDA issues new safety rules for vitamins

KEVIN FREKING, Associated Press Writer 6-22-2007

WASHINGTON - For the first time, manufacturers of vitamins, herbal pills and other dietary supplements will have to test all of their products' ingredients.
The Food and Drug Administration said Friday it is phasing in a new rule that is designed to address concerns that existing regulations allowed supplements onto the market that were contaminated or didn't contain ingredients claimed on the label.

Last year, the agency found that some supplements contained undeclared active ingredients used in prescription drugs for erectile dysfunction. In the past, regulators found supplements that didn't contain the levels of Vitamin C or Vitamin A that were claimed.

If, upon inspection, the FDA finds that supplements do not contain the ingredients they claim, the agency would consider the products adulterated or misbranded. In minor cases, the agency could ask the manufacturer to remove an ingredient or revise its label. In more serious cases, it could seize the product, file a lawsuit or even seek criminal charges.

Dietary supplements, pills, liquids or other products are a $22 billion industry.

Most companies already test their raw ingredients, said Steve Mister, president and CEO for the Council for Responsible Nutrition, a trade association representing about 65 manufacturers.

"This raises the bar so that all have to comply," Mister said.

The new rule goes into effect Aug. 24 and will have a three-year phase-in that gives smaller manufacturers more time to comply. Even the largest of the manufactures won't have to comply until June 2008.

The rule applies to all domestic and foreign companies that manufacture, package and label supplements for sale in the U.S. It requires them to analyze the identity, purity and strength of all the ingredients that go into their products before they are distributed.

It also includes requirements for record keeping and handling consumer complaints.

Dr. Sidney Wolfe, who has testified before Congress on problems with dietary supplements, said the new rule does not ease his concern that unsafe supplements are too easy to bring to market.

"You still don't have to show the product is safe. You don't have to prove it works," said Wolfe, director of Public Citizen's Health Research Group.

Consumers Union, publisher of Consumer Reports, called the rule a good step toward improving consistency in the ingredients that go into supplements.

"However, consumers still have no idea if a given product works, or whether it is dangerous," said Janell Mayo Duncan, senior counsel for Consumers Union, publisher of Consumer Reports.

Congress limited the Food and Drug Administration's oversight of vitamins and other dietary supplements in 1994. The new rule is a product of that law, meaning that the rule took nearly 13 years to develop.

Under the old regulations, supplements were governed by the same rules that applied to producing foods, such as cans of soup.

"The final rule will help ensure that dietary supplements are manufactured with controls that result in a consistent product free of contamination, with accurate labeling," said Dr. Robert E. Brackett, director of FDA's Center for Food Safety and Applied Nutrition.

~More drugs hobble restless legs syndrome

An investigational dopamine agonist, is being studied for
treatment of restless legs syndrome. Jun 4, 2007 By: Kelly Dowhower Karpa, Ph.D., R.Ph. Drug Topics

A leading theory regarding the pathophysiology of primary restless legs syndrome (RLS) suggests that abnormalities of dopaminergic function may be involved. Consistent with this thinking, dopamine receptor agonists are often used in therapeutic management of RLS. In
May 2005, ropinirole (Requip; GlaxoSmith-Kline) became the first drug approved by the Food & Drug Administration for RLS, followed by pramipexole (Mirapex, Boehringer Ingelheim) in November 2006. RLS, a sensory disorder, causes an irresistible urge to move the legs. Up to 10% of American adults may be affected.

Another investigational dopamine agonist, rotigotine-delivered via a transdermal patch-has been studied for both RLS and Parkinson's disease and, as Neupro (Schwarz Pharma), was just approved for arkinson's. "The patch releases the drug continuously, with no drop in drug levels during early morning hours, so rotigotine should have less of a 'wearing-off effect' in the morning compared with other dopamine agonists," said Jack Chen, Pharm.D., associate professor in
the movement disorders clinic at Loma Linda School of Medicine and Pharmacy in Southern California. This would prevent a recurrence of symptoms in the morning, a phenomenon sometimes seen with current dopaminergic therapies.

According to product labeling for dopamine agonists, hypotension may occur-even resulting in syncope. Dopamine agonists have also been associated with compulsive behaviors. But, as Chen noted, "they are
not dose-related and they are clearly a class effect," as compulsions have occurred with both pramipexole and ropinirole.

New-generation dopamine receptor agonists like ropinirole and pramipexole target receptors located within brain regions that control motivation, emotion, and reward behaviors. In at least a subset of patients, stimulation of these receptors can prompt pleasure-seeking behaviors. Because of this, experts are now
recommending that all patients with RLS be screened by physicians for compulsive behaviors prior to therapy with dopamine agonists. Family and friends of patients should report all negative behaviors to the patient's physician, suggested Maja Tippmann-Peikert, M.D., a
neurologist at the Mayo Clinic in Rochester, Minn., and lead author of an article in the Jan. 23 issue of Neurology on this subject.

Although the precise mechanism by which it acts in RLS management is unknown, gabapentin is used off label for treating RLS. In several small clinical studies in which gabapentin was studied in patients with RLS, the antiepileptic drug improved sleep quality and sleep
latency and reduced leg movements during sleep. In fact, in several of the studies, gabapentin was just as effective as dopamine-acting drugs.

"Gabapentin might be used in RLS management when there is a simultaneous neuropathic pain component. Additionally, gabapentin might be added if patient are not getting adequate relief from a dopaminergic drug," said Chen.

Capitalizing on the benefits of gabapentin, Xenoport Inc. andGlaxoSmithKline have partnered to develop and commercialize a unique prodrug of gabapentin, known at this point only by the chemical name XP13512. This new drug reportedly has improved bioavailability
compared with gabapentin.

Gabapentin is absorbed in the upper portion of the small intestine by a transporter that is easily saturated. This causes absorption of gabapentin to be dose dependent and to vary widely between patients.
Rapid clearance of the drug also necessitates dosing three or more times per day to maintain therapeutic levels.

In contrast, XP13512 was designed to be absorbed throughout the length of the intestines, and when XP13512 is delivered via a sustained-release formulation, extended exposure to the drug enhances
colonic absorption.

Although clearly the pharmacokinetic properties differ between gabapentin and XP13512, Chen cautioned that "it is too soon to tell whether XP13512 will offer clinical advantages over gabapentin" for RLS management.

THE AUTHOR is a clinical writer based in the Philadelphia area.Source:


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