Wednesday, December 21, 2011

Fibromyalgia and Mitochondrial Dysfunction

Dr Myhill on Fibromyalgia and Mitochondrial Dysfunction
by Sarah Myhill, MD*
December 21, 2011

Dr. Sarah Myhill is a UK-based physician with a special interest in fatigue and nutrition. Her pioneering research (“Chronic Fatigue Syndrome and Mitochondrial Dysfunction”) suggests the cells’ energy generating mitochondria are dysfunctional in ME/CFS – a situation that can produce various symptom clusters, including: a) blood flow/vascular abnormalities such as orthostatic intolerance, b) the widespread pain and sensitization most typical of fibromyalgia syndrome, and c) fatigue, exhaustion & brain fog. This information is excerpted with kind permission from (*


Fibromyalgia – Possible Causes and Implications for Treatment

The word ‘fibromyalgia’ just refers to a symptom - it means pain in the muscles. It occurs very commonly with chronic fatigue syndrome [ME/CFS] because I suspect the underlying causes are similar.

How Energy is Produced in Cells

All cells require energy in order to work. There are two ways that they can get their energy.

Energy Production Using Oxygen. Normally, energy is supplied to cells by mitochondria (little organelles within cells) which supply energy in the form of Adenosine Triphosphate (ATP) via a process called Oxidative Phosphorylation. This process requires oxygen, is extremely efficient, and is the way in which the vast majority of energy is produced the vast majority of the time. You might enjoy watching a very interesting presentation on oxidative phosphorylation (which starts with NADH and Ubiquinol CoQ-10) - published on the website of Purdue University, Indiana.

Energy Production Using Sugar. The second way in which cells can get energy is through Glycolysis.  From an evolutionary point of view this is a very much more primitive way of supplying energy. It does not require oxygen, it just needs sugar. It is extremely inefficient and the result of glycolysis is the production of large amounts of lactic acid.

All athletes recognize the moment when they switch from aerobic metabolism (requiring oxygen) via mitochondria to anaerobic metabolism (glycolysis) resulting in a build up of lactic acid. It is this build up of lactic acid that causes the pain, heaviness, feeling exhaustion, deadened muscles, and muscles will not work or go any faster sensation.

I am also interested in this idea because in horses there is a condition known as azoturia (tying up), which does not have an obvious human parallel. I suspect, however, that this parallel is fibromyalgia. This condition occurs in some susceptible horses when there is a huge build up of lactic acid in their muscles which causes extremely severe muscle damage, massive amounts of pain and distress and in severe acute cases the horse can die from it.

So What Goes Wrong in Fibromyalgia?

I suspect that in fibromyalgia there is an inappropriate switch from aerobic mitochondrial production of energy (via oxidative phosphorylation) to glycolysis (very inefficient anaerobic production of energy, not requiring oxygen, but with a large build up of lactic acid).

Lactic acid in the short term causes immediate muscle pain. Normally this is remedied by the person slowing down or stopping because of that pain, cells switch back into aerobic metabolism and the lactic acid is quickly cleared away and got rid of. All athletes know that when they stop running the horrible painful sensation in their legs will be gone within a few seconds or minutes.

This does not happen in fibromyalgia because:
• The sufferer can't make ATP quick enough to shunt lactic acid back to acetate (via the Cori Cycle, aka Lactic Acid Cycle; more on this below).

• And the sufferer is completely pole axed by ongoing lactic acid burn with inability to move,

• And possibly secondary damage from lactic acid which, for example, is good at breaking down the collagen matrix which holds cells together. That is to say, the lactic acid may cause microscopic muscle tears, which would present as local areas of soreness and would trigger a process of healing and repair by the immune system.
There would also be excessive release of free radicals as the immune system repairs. This may well cause further muscle damage and - in people with poor antioxidant system - this is a disease amplifying process. Some sufferers find vitamin B-12 helpful, possibly because it is acting as a scavenger of free radicals.

1. The most obvious reason for this of course is mitochondrial failure, which I believe is a major cause of chronic fatigue syndrome.

If mitochondria cannot supply sufficient energy to cells, cells will switch into glycolysis with a resultant build up of lactic acid. In the heart, this switch into anaerobic metabolism because of mitochondrial failure will present with angina (chest pain). There are many causes of mitochondrial failure (see handout - causes of CFS, mitochondrial failure and mitochondrial function test) such as:
• Lack of nutrients for mitochondria to work (D-ribose, magnesium, vitamin B3 (niacin), co-enzyme Q10 and acetyl L-carnitine). [Note: A trial due to start in early 2012 at Columbia University will test the ability of selected nutraceuticals to help manage lactate levels and other aspects of mitochondrial dysfunction in ME/CFS.]

• Toxic stress (which is blocking oxidative phosphorylation, or blocking translocator protein function),

• Poor antioxidant status (so mitochondria are damaged by biochemical activity),

• Poor hormonal control (poor levels of thyroid or adrenal hormones) and so on.
2. Lack of oxygen to muscles may be another reason for the switch to glycolysis.

A fascinating paper in the Lancet by John Yudkin explains how a high carbohydrate diet could cause high blood pressure. [As a long-time professor of nutrition and dietetics at the University of London, he was an early advocate of low carb Atkins-type diets]. Dr. Yudkin demonstrated that high levels of sugar in the blood were very damaging to muscles, and the body compensates for this by shutting down the blood supply to muscles when blood sugar levels are running too high.

Whilst this protects muscles from damage by sugar, it restricts oxygen supply to that muscle. One can see how if that muscle were asked to suddenly work quite hard, it would rapidly switch into glycolysis with production of lactic acid.

Therefore I suspect high carbohydrate or high sugar diets are a risk factor for fibromyalgia. In horses with azoturia, a high carbohydrate diet is a known risk factor.

3. Exercise - too much or too little!

Muscles are extremely dynamic organs. Blood is obviously supplied to them by the heart. However, for blood to come out of muscles requires the muscle itself to contract.

Thanks to a serious of valves within veins, when muscles contract they squeeze the blood out of themselves; then as they relax, the muscles fill with blood from the heart; and then as they contract, the blood is pumped out of them again.

Indeed, during exercise, it is this alternate muscle contraction and relaxation that is largely responsible for the circulation of blood through the muscle. That is to say, the muscles like being worked - it is essential for good blood supply and it is essential to move out and excrete toxins (such as lactic acid), which inevitably build up in muscles when they are being used.

The problem for people with fatigue syndromes is that they do not have sufficient energy to exercise their muscles and therefore bring an adequate blood supply to their muscles, and this alone causes muscle problems.

This is compounded in severe CFS where cardiac output is poor because of mitochondrial failure in heart muscle! For example, if there is too much build up of toxins in muscle, the reflex response of that muscle is to go into spasm. If that muscle goes into spasm and remains in spasm (i.e., a cramp), then the circulation is further impaired and there is sudden and quick build up of toxic metabolites, which causes more pain and spasm.

This is exactly what happens in horses with azoturia (hence its other name 'tying up'). There is so much muscle spasm and pain that the horse is literally unable to move and there is a huge amount of tissue damage going on.

Obviously humans do not push themselves to the extremes that horses do and so we do not see this same acute clinical picture, but I suspect the underlying biochemistry is the same.

4. The Cori Cycle (aka Lactic Acid Cycle)
• In converting glucose to lactic acid, 2 molecules of ATP are produced.

• To get rid of lactic acid, it has to be converted back to glucose, but this requires 6 molecules of ATP.

• When energy in the form of ATP is in such short supply, lactic acid hangs around much longer and is more damaging.
Implications for Treatment

1. Treatment of mitochondrial failure as per handout.

My experience so far is that:
• This works reliably well, though it takes months to respond, not weeks.

• But improvement is sustained month on month.

• What gets in the way is allergy - that is to say, tolerating the supplements.
2. Eat a low carbohydrate, low sugar diet.

Most calories should come from protein, fat and complex carbohydrates requiring gut fermentation by probiotics - these ferment carbohydrates into short chain fatty acids, which are the desirable fuel for mitochondria.

3. The muscle problem.

There is a fine balance to be judged here! When the muscle is in acute spasm and in pain, the worst thing you can possibly do is to exercise it because it will simply make everything much worse. However, the muscle does require blood circulation in order to heal and repair, and this can be encouraged by:
• Muscle relaxants (such as diazepam),

• Improving trace mineral status (imbalance of magnesium, calcium, sodium and potassium can cause a tendency to cramp and muscle spasm),

• Heat (to improve blood supply),

• And ideally massage or toning tables. The idea here is that the muscle is gently and rhythmically squashed, which therefore improves the circulation of the muscle, but without the muscle having to do any work.

• Painkillers may be helpful because the body's response to pain is muscle spasm.
However, if the muscle feels completely fine and is not painful at all, then it should be exercised gently on a daily basis. Obviously, the more exercise one can tolerate the better, but as soon as it switches into pain, you must stop or you simply make the situation much worse.

Gentle daily use of the muscles, therefore, improves the circulation and helps the muscle to clear toxic metabolites which trigger the above problems. This may be why yoga or Pilates exercises are often helpful in fibromyalgia.

However, do not use painkillers to allow exercise - this may make things much worse!

4. Improve antioxidant status.

As soon as muscle starts to become painful and release toxic metabolites, there is secondary muscle damage by free radicals. Having good antioxidant status helps protect against this secondary damage. The obvious antioxidants to measure which I check on a regular basis are: Co-enzyme Q10, glutathione peroxidase, and superoxide dismutase. [See "A Primer on Antioxidants and Free Radicals."]

There is one antioxidant which has been trialed in horses with good results called astaxanthin, and the dose for humans would be 4mg daily. [See “Astaxanthin – A little-known but power-packed nutrient.”]

5. Iodine deficiency.

This may present with fibromyalgia. [See “Iodine – What is the correct daily dose?”]

Monday, December 19, 2011

Physical Therapy for chronic pain

KALISPELL, MT., (PRWEB) December 19, 2011 

While many people associate physical therapy solely with injury rehabilitation, Professional Therapy Associates analyzed its physical therapy services to determine the percentage of patients undergoing rehabilitative therapy versus other forms of treatment. The Northwest Montana physical therapy practice found that approximately half of its patients are receiving treatment for injury, illness or post-surgery rehab, while the remaining half are using physical therapy to address a variety of other conditions or attain health, fitness and lifestyle goals.

“Physical therapy is widely recognized for its effectiveness in helping patients recover and regain full mobility after an injury, severe illness or surgery. However, it’s a common misconception that physical therapy is only used for rehabilitative purposes – statistically, one in two patients visit us for reasons other than rehab,” said Blaine Stimac, owner and CEO of Professional Therapy Associates. “Our physical therapists are experts at rehab therapy, but they also treat patients for conditions ranging from chronic pain, arthritis and repetitive strain to headaches, sleep problems and balance issues. They also provide strength, flexibility and endurance training to athletes and individuals looking to improve their overall health and fitness.”

Physical therapists undergo extensive training in biomechanics and the musculoskeletal system, which is why they are qualified to help patients increase mobility, alleviate pain and improve fitness. Stimac elaborated on some of the physical therapy services his team provides beyond injury and surgery rehabilitation:
  • Back Pain – “Many people immediately think of chiropractors when they have back pain, but physical therapy can effectively treat back pain as well as pain in adjacent areas, such as the neck, shoulders and hips,” explained Stimac. “Some people find that their back pain returns even after being treated by a chiropractor. This often happens when a chiropractor is correcting the issuing but not providing the necessary stabilization. This is where a physical therapist can help.”
  • Arthritis – Stimac notes that individuals with arthritis often have stiff joints because they avoid movements that may exacerbate their pain. However, by not moving or exercising those joints, arthritis sufferers often find the pain and stiffness only get worse. Physical therapists can teach patients exercises that will minimize pain and stiffness, and strengthen muscles that support the joints.
  • Desk Pain – Professionals who work with computers or at a desk often suffer from a host issues as a result of sitting for hours in a fixed position and performing repetitive movements. Physical therapy can assist with many different types of work-related pain – from back pain and neck stiffness to headaches and repetitive stress injuries. Not only will physical therapists help to ease patients’ pain, but they will also demonstrate how to avoid related problems in the future.
  • Sleep-Related Issues – According to Stimac, many individuals experience fatigue or have difficulty sleeping as a result of chronic pain. Conversely, there are others who may sleep well but in awkward positions that cause neck and shoulder pain during their waking hours. He explains that physical therapists are skilled in determining the cause of such conditions, and can provide treatments, exercises and advice that will help resolve the issue.
“When patients come to us with chronic pain or other complaints, we’ll identify the underlying cause, alleviate their pain or discomfort, and show them how to fix whatever is creating the problem in the first place,” said Stimac. “I would encourage anyone experiencing pain, stiffness or limited mobility to schedule a physical therapy evaluation. Montana residents can request a free consultation at any of our four Flathead Valley physical therapy clinics if they’d like to learn more about our treatments and explore whether physical therapy is the right choice for them.”

For additional information on Professional Therapy Associates – including details on its rehabilitative treatments and other physical therapy services, as well as contact information for its clinics in North Kalispell, Downtown Kalispell, Whitefish and Columbia Falls – please visit

About Professional Therapy Associates and Blaine Stimac

Professional Therapy Associates (PTA) is an established provider of physical therapy in Montana. Founded in Kalispell in 1988, the practice has expanded to include four convenient locations throughout Flathead Valley. In addition to its flagship Kalispell North facility, PTA also has clinics in Downtown Kalispell (Flathead Health and Fitness), Whitefish (The Wave) and Columbia Falls (Columbia Falls Clinic). Owner and CEO Blaine Stimac is a licensed Physical Therapist in Montana, and holds a Master of Science in Physical Therapy from the University of Montana. He and his team offer a full range of services, including manual physical therapy, sports medicine, therapeutic exercise and biofeedback, as well as treatment for back and neck injuries, motor vehicle injuries and work-related injuries. For more information, visit

Thursday, December 15, 2011

New TMJ study may answer questions about pain

A new study about painful jaw problems could lead to a better understanding of chronic pain and pain disorders.

The results, recently published in the Journal of Pain, provide insights into potential causes of temporomandibular joint and muscle disorders, known as TMJ. Researchers believe their work, the first large scale study of its kind, could lead to new methods of diagnosing facial pain, predicting who is susceptible to them and new treatments.

TMJ is not a single condition, but rather a group of conditions, categorized by acute pain in the jaw joint and chronic pain in the facial area. This cluster of jaw problems is the second most common occurring musculoskeletal condition that can lead to disability, trailing only chronic lower back pain. TMJ radiates through the jaw and muscles, causing pain and tightness in the jaw, neck, and ear. Symptoms include aching facial pain, difficulty chewing, ear aches, pain and tenderness in the jaw, headache, jaw locking, and an uncomfortable or uneven bite.

Researchers with the Orofacial Pain Prospective Evaluation and Risk Assessment study (OPPERA) followed an initial group of 3,200 pain-free people, aged 18 to 44, between three and five years. They found that chronic pain TMJ increased with age in women but not in men. This finding overrode assumptions that pain was greatest in childbearing years for women but decreased with age. The study also found genetic factors that were linked to chronic TMJ. These genes were identified, resulting in the possibility of creating drugs for these and other chronic pain conditions that are related to TMJ.

“This novel study will also allow us to learn more about pain disorders in general, and will improve our ability to diagnose and treat chronic pain conditions across the board,” said Dr. William Maixner, program director for the study and director of the Center for Neurosensory Disorders at the University of North Carolina at Chapel Hill School of Dentistry. “OPPERA is allowing us to study potential biological, psychological and genetic risk factors over a longer period of time, so we will be able to better evaluate the association of these factors.”

While trauma is often the cause of TMJ, there are many times when the cause isn’t clear. The Mayo Clinic states that some of the reasons for jaw pain, tightness, and clicking include the disk eroding out of alignment, a damaged joint, arthritic damage to the cartilage of the joint and fatigued muscles that should be stabilizing the joint. Simply put, even every day occurrences such as grinding your teeth at night or clenching your jaw may lead to the condition.

Perhaps the most outstanding finding in the study was finding a range of biological and psychological factors that contribute to the pain of the condition. People with TMJ are more sensitive to pain, even just mildly painful stimulation, than those that do not have the condition. They have a higher heart rate that increases greater during stress. They are also more aware of their body’s sensations than those without TMJ. These findings may conclude that TMJ is partially connected to the ability to suppress pain and the perception of pain.

Tuesday, December 13, 2011

Why the focus on medical cannabis?

I know it seems like I've been posting a lot about medical cannabis lately, but there are several studies being publicized at this time.  I believe, if it works, it works, so I have no problem with publicizing these studies and writing about medical cannabis.  I will soon be focusing on other areas of treatment of chronic pain, and have in my past posts.  A number of topics can be found in the archives.

Monday, December 12, 2011

Cannabis and California’s Physicians: A New Perspective

The following statement appears in the December edition of San Francisco Medicine, the journal of the San Francisco Medical Society.

Time for New Perspectives


Steve Heilig, George Fouras, Donald Abrams, and David Pating

There has long been a “drug war” surrounding marijuana, not only in terms of the plant’s legal status but also in words.  As the California Society of Addiction Medicine observes, “Reasonable dialogue regarding marijuana use has historically proven extraordinarily difficult.”  The result is a longstanding stalemate and various symptoms of “reefer madness,” but with a growing consensus that our nation’s marijuana policy has not served us much better than the failed experiment with alcohol prohibition many decades ago.

Most recently, there was this headline: “California Medical Association calls for legalization of marijuana.” It was a cover story in the Sunday Los Angeles Times in October. As the CMA is a large, mainstream medical society, this caused quite a stir.

The four authors of this article served as San Francisco’s representatives on the CMA’s “Technical Advisory Committee” (TAC) tasked with drafting “a comprehensive white paper recommending policy on marijuana legalization and appropriate regulation and taxation.”  The TAC was “selected to represent CMA in the areas of science, ethical affairs, public health, addiction medicine, and expertise in the use of cannabis.”  We met five times; the deliberations were sometimes contentious but each member agreed sufficiently to endorse a final report to the CMA board of trustees.

Our 14-page report, titled “Cannabis and the Regulatory Void”, was submitted to the CMA’s Board of Trustees and approved, unanimously, in October. Reactions from all sides were immediate.  The CMA was called “irresponsible” and at least one opponent utilized the cliché “What are they smoking?”  But there has also been much positive response as well, with editorials saying we took “a bold step” towards “a prescription for the medical pot mess” and that that the CMA’s “traditionally conservative doctors” are “simply acknowledging the obvious: Our current laws and the resulting war on drugs aren’t working.

“1. Impact on Cannabis use:  The primary concern regarding “legalization” or any lessening of legal penalties regarding cannabis is that it might increase use, particularly among teens.  We share such concerns, especially in light of growing evidence regarding negative effects on neurodevelopment.  But there is no good evidence that laws have much effect on use; in fact, long evidence is that our punitive approaches have little deterrent effect.  Thus we should seek approaches which maximize knowledge about the impacts of cannabis use, and which do not worsen the problem by criminalizing otherwise law-abiding people, kicking kids out of schools to no productive end, wasting resources, and hampering research.  Evidence-based drug education is difficult but likely to be at least as effective as legal approaches – and likely more so.

2. Resources and costs:  Enforcing largely futile laws is expensive, especially when prison is involved.  Appropriate treatment and education is far more cost-effective. While our report recommends an approach closer to that taken towards alcohol, at least for adults, we have no illusion that such an approach is easy or ideal, or that the taxation we endorse will be a simple matter or yield massive funding.  But we are confident that it will be more cost-effective than longtime, failed “drug war” or prohibition-type policies.  And very importantly, the funds saved and generated should be directed towards treatment of addiction.

3. Medical Marijuana: We join the many experts and organizations holding that cannabis be placed in a less restrictive category that would facilitate more research.  And while we support some legal medical use of cannabis such as allowed since 1996 in California, we note that a decriminalization approach would have the salubrious effect of lessening or even eliminating the need for physicians to serve in the oft-uncomfortable “middle man” role of “gatekeeper” for medical use of cannabis – and also allow for more rigorous regulation of questionable practices at “cannabis dispensaries.”

An ever-growing roster of medical, legal, political, and other authorities of all political stripes feel that the time has come for a serious change in our drug laws, especially with respect to cannabis.  We have joined them, as has the CMA.

Interestingly enough, another new CMA policy was independently adopted this year, which could have served as a preamble to our own report:

MEDICAL VS. LEGAL SOLUTIONS TO DRUG ABUSE: CMA encourages the federal government to re-examine the enforcement- based approach to illicit drug issues (“war on drugs”) and to prioritize and implement policies that treat drug abuse as a public health threat and drug addiction as a preventable and treatable disease.

We agree, and know that many others do as well.  We hope our elected leaders will listen.

***Steve Heilig is with the San Francisco Medical Society and editor of the Cambridge Quarterly of Healthcare Ethics.  George Fouras is a child and adolescent psychiatrist and President of the San Francisco Medical Society; Donald Abrams is chief of Hematology-Oncology at San Francisco General Hospital and a leading medical cannabis researcher at the University of California, San Francisco; David Pating is an addiction psychiatrist and past-president of the California Society of Addiction Medicine. Their opinions here are their own and not necessarily representative of their affiliated organizations.
For more information:
The California Society of Addiction Medicine:

Sunday, December 11, 2011

Speaking out against a stigma

Terry Bremner smokes his marijuana pipe in Halifax parking lots and quiet woods, even though he is legally allowed cannabis to dull the pain of fibromyalgia.

Until now, his two adult sons didn't know. Nor did his neighbours, or the parents of the preteen football players he coaches.

But he thinks it's time to speak up against the stigma that lumps medical users with recreational ones.
As president of the Chronic Pain Association of Canada, headquartered in Edmonton, Bremner, 50, visits chronic pain sufferers across the country talking about marijuana as a medical option, especially for those who experience side-effects from strong opioids.

"I was begging for pain meds," said Bremner, who was 34 and working in St. Albert when he was in a head-on collision in 1995. Doctors didn't diagnose him with a mild traumatic brain injury and fibromyalgia until two years later.

Bremner tried Tylenol 3s, morphine, Demerol and Prozac. A psychiatrist suggested shock treatment.
Instead, Bremner started sneaking off for a joint, which helped interrupt his fixated thoughts of pain, his worries about making ends meet and his fight for benefits.

When Bremner moved back to Nova Scotia in late 1997 with his wife and two children, he couldn't find a doctor willing to take on his complex needs. Initially he turned to the streets to get his small supply.
His supplier got busted.

Then, his wife found out. "She wasn't impressed," he said.

At least not until he discovered the compassion club in Halifaxthat sold marijuana illegally to people with documented health problems - and then only in clandestine handovers.

Bremner could only afford 10 grams a month, and would quickly run out. He enrolled in a two-year study to try the government's marijuana. "It was total garbage," he says, but it was free.

Eventually, Bremner got his federal licence to use the drug. He has been waiting two months for a renewal. Then he will once again order his supply from Victoriabased MedMe, a company that supplies multiple strains of marijuana.

Bremner looks for the right combination of Sativa strains, to boost energy, and Indica strains, to bring sleep and relaxation. Some types help with chronic pain; others work better for patients with cancer, HIV or other severe diseases. Health Canada's one-size-fitsall approach simply isn't adequate, Bremner said.
His wife now understands the medical need. Bremner plans to explain it soon to his two sons.

"I have been asked to be a voice" for chronic pain sufferers, Bremner said. "Maybe it will attract more attention to help more individuals, people like myself who need this medication."

Thursday, December 8, 2011

Researchers seek Chronic Fatigue patients for study

Participants needed to take part in study, the first to look in-depth at vision problems caused by the disorder 

Researchers from the University of Leicester have launched a new study into vision problems suffered by patients with Myalgic Encephalopathy (ME) or Chronic Fatigue Syndrome (CFS). People who suffer from ME/CFS typically experience a range of symptoms which may include extreme tiredness, painful joints, headaches and digestive problems.

The team from the University of Leicester's School of Psychology is undertaking the first study to look in-depth at visual issues in ME/CFS patients. The researchers hope that collecting medical evidence of such symptoms could aid in the diagnosis and treatment of ME/CFS.

There is little consensus on the cause of ME/CFS or on how to treat patients with the condition. Although vision problems are widely reported by ME/CFS sufferers, research in this area is scarce and little formal evidence of such issues has been documented.

The researchers are actively looking to recruit participants to take part in the study.
Steve Badham, who is running the study, said: "This project provides us with an excellent opportunity to study the link between vision and ME/CFS. Understanding this relationship will allow us to better differentiate between ME/CFS and other conditions, and to learn more about the symptoms that patients are suffering from."

The University of Leicester team hopes to investigate a range of basic visual problems commonly reported by ME/CFS sufferers, such as hypersensitivity to light and difficulties focussing on and tracking objects.

ME/CFS affects around 250,000 people in the UK alone. The main symptom is persistent fatigue and tiredness that doesn't go away with rest and has no obvious cause. Sufferers may also experience other symptoms and can find themselves unable to work or take part in activities. Gathering hard evidence of the symptoms and effects of ME/CFS can aid in treatment and diagnosis and help raise the profile of this debilitating illness.

The diagnosis of ME/CFS has been a controversial one for many years, because the cause of the condition is currently unknown. Suggested treatments for ME/CFS include psychological interventions such as behavioural therapy, and medication such as painkillers and low dose antidepressants. There is no known cure for ME/CFS.

The researchers are looking for anyone with a medical diagnosis of ME or CFS to get in touch if they wish to help out with the study. Participants will take part in the study at the University, involving visual tests and tasks on a computer. You can contact Steve Badham by email ( or telephone (0116 229 7081) for more information about volunteering. Even if you don’t think you suffer from a vision problem, you may still be eligible to take part.

Wednesday, December 7, 2011

Pot, narcotics OK to treat chronic pain

Inhaled marijuana appears to be a safe and effective treatment for chronic pain when used in addition to narcotics like morphine and oxycodone, according to a small UCSF study that is the first to look at the combined effects of the two classes of drugs in humans.

The study, published in this month's edition of Clinical Pharmacology and Therapeutics, was designed primarily to look at whether taking marijuana with narcotics is safe, and researchers reported that there were no negative side effects from combining the drugs.

Overall, the 21 men and women in the study reported a roughly 25 percent reduction in pain after inhaling vaporized marijuana several times a day for five days.

If the results can be backed up in further studies, marijuana could prove an important means of augmenting the effects of narcotic drugs for the millions of people who suffer from chronic pain associated with cancer, AIDS and a variety of other conditions, said study author Dr. Donald Abrams, a UCSF professor and chief of the hematology-oncology division at San Francisco General Hospital.
"If we can get funded, we should do a study now with pain as the endpoint" and not just safety, Abrams said.

He added that scientists don't yet understand how, exactly, marijuana and opiates interact in humans, but "our results support that the relationship between cannabis and opiates is synergistic."

Multiple studies of medical marijuana have shown that the drug can be beneficial in treating pain. A drug called Sativex that combines the two main compounds of marijuana - cannabidiol (CBD) and delta-9 tetrahydrocannabinol (THC) - is currently in clinical trials for treatment of pain in cancer patients in the United States, and is already used in Europe and Canada.

Stands to reason

With what's already known about marijuana's pain-relieving effects, it's not surprising that the drug, when used with narcotics, would increase pain relief, said researchers not associated with the new study.

"There's already tons of data on cannabinoid pain relief and opiate pain relief, and it only makes sense that you'd get more pain relief from two drugs instead of one," said Dr. Daniel Nomura, an assistant professor in the nutritional sciences and toxicology department at UC Berkeley.

Abrams himself pointed out that because his study is small, and because all of the patients knew they were inhaling marijuana and therefore could have experienced some pain relief from a "placebo effect," it would be premature to start widely prescribing cannabis to pain patients. Still, the results were promising enough that he intends to attempt a second study to look more closely at pain relief.

But getting another study off the ground will be tough. The bar has been set high for acceptable uses of medical marijuana, Abrams said, and getting money and other resources - notably, the drug itself - to conduct research can be very difficult. Abrams' study was funded by the National Institute on Drug Abuse, which also supplied the marijuana.

The patients in Abrams' study were taking twice-daily doses of either morphine or oxycodone to treat chronic pain associated with a variety of conditions, such as arthritis, neuropathy, cancer and multiple sclerosis.

Patients stayed at San Francisco General Hospital during the study. They inhaled vaporized marijuana three times a day, for about 10 minutes at time. On the first day of the study, the mean pain score, on a scale of 0 to 100, was 39.6; after five days of marijuana therapy, their mean pain score was 29.1.

Ideal outcome

The hope, Abrams said, is that marijuana could someday be used either in conjunction with narcotics or as a replacement for narcotics to help curb some of the side effects associated with those medications.
Glenn Osaki of Pleasanton, a patient of Abrams who used to take drugs like morphine and oxycodone daily, said he's been off narcotics since July 2010, after he started using medical marijuana to combat pain associated with colon cancer.

"I was out of it most of the time from the opiates," said Osaki, 53. "It was hard having a decent quality of life, and I was just trying to figure out a way to manage my pain."

Medical marijuana has only one side effect he doesn't care for: the high.

"I used to smoke pot when I was a kid, just goofing around," he said. "The stuff nowadays is pretty strong, so that is one thing I don't really like now."

At UC Berkeley, Nomura agrees. He and other biologists are studying ways to tap into the useful effects of cannabis without the drug high that comes with it.

"Obviously medicinal marijuana is still widely used. There are really undisputed beneficial effects," Nomura said. "But in terms of moving forward with drug development, we need to develop safer drugs that don't make you high."

Monday, December 5, 2011

Cannabis slows cancer in test tube

Marijuana Ingredients Slow Invasion by Cervical and Lung Cancer Cells

Dec. 26, 2007 -- THC and another marijuana-derived compound slow the spread of cervical and lung cancers, test-tube studies suggest.

The new findings add to the fast-growing number of animal and cell-culture studies showing different anticancer effects for cannabinoids, chemical compounds derived from marijuana.

Cannabinoids, and sometimes marijuana itself, are currently used to lessen the nausea and pain experienced by many cancer patients. The new findings -- yet to be proven in human studies -- suggest that cannabinoids may have a direct anticancer effect.

"Cannabinoids' ... potential therapeutic benefit in the treatment of highly invasive cancers should be addressed in clinical trials," conclude Robert Ramer, PhD, and Burkhard Hinz, PhD, of the University of Rostock, Germany.

Might cannabinoids keep dangerous tumors from spreading throughout the body? Ramer and Hinz set up an experiment in which invasive cervical and lung cancer cells had make their way through a tissue-like gel. Even at very low concentrations, the marijuana compounds THC and methanandamide (MA) significantly slowed the invading cancer cells.

Doses of THC that reduce pain in cancer patients yield blood concentrations much higher than the concentrations needed to inhibit cancer invasion.

"Thus the effects of THC on cell invasion occurred at therapeutically relevant concentrations," Ramer and Hinz note.
The researchers are quick to point out that much more study is needed to find out whether these test-tube results apply to tumor growth in animals and in humans.

Ramer and Hinz report the findings in the Jan. 2, 2008 issue of the Journal of the National Cancer Institute.

Tuesday, November 29, 2011

Risk of fibromyalgia tripled in women with sleep problems

By Anne Harding
Women plagued by sleep problems have more than triple the risk of developing the pain disorder fibromyalgia compared to their better-rested peers, a new study from Norway suggests.
The more often a woman experienced insomnia and other sleep problems, the more likely she was to have developed fibromyalgia 10 years later, according to the study, the largest to date to follow women who were initially free from chronic pain.

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The findings imply that sleep problems may lead to fibromyalgia, but the researchers say the relationship isn't so clear-cut. Although sleep deprivation has been shown in previous research to increase inflammation and reduce the body's ability to manage pain, experts haven't been able to draw a straight line from sleep difficulties to fibromyalgia.

"Sleep problems are just one factor that may contribute to the development of fibromyalgia," says Paul J. Mork, Ph.D., a study coauthor and a researcher at the Norwegian University of Science and Technology, in Trondheim. "Fibromyalgia is a complex pain syndrome and there are numerous other factors that may contribute to the development of this illness."
Doctors have long been aware of the link between poor sleep and fibromyalgia, a chronic condition characterized by widespread pain and tender points in the soft tissues. Fibromyalgia patients -- more than 90 percent of whom are women -- nearly always report trouble sleeping, while poor sleep is in turn associated with worse pain. (A 1975 experiment found that depriving healthy volunteers of sleep caused them to develop fibromyalgia-like symptoms.)
"In the clinic we really do see a reciprocal relationship between fibromyalgia and sleep quality," says Lesley Arnold, Ph.D., a professor of psychiatry and behavioral neuroscience at the University of Cincinnati College of Medicine. "Pain can affect your sleep; it results in poor sleep for many patients, and that in turn increases the pain and results in the persistence of the problem."

The new study, which was published in the journal Arthritis & Rheumatism, included 12,350 women age 20 and older who had no fibromyalgia, muscle or bone pain, or other physical impairments when the study began, in the mid-1980s. When the researchers surveyed the women again, in the mid-1990s, roughly 3 percent reported that they had developed fibromyalgia.
At the study's outset, roughly two-thirds of the women said they had no difficulty sleeping. Compared with that group, those who said they "sometimes" had trouble falling asleep or had any sleep disorder during the previous month had double the risk of developing fibromyalgia. The risk was three and a half times greater among those who said they "often or always" had sleep problems.
The link appeared to be especially strong among women age 45 and older. Women in that age group who reported often or always having sleep problems had a more than fivefold increased risk of fibromyalgia compared to sound sleepers, while the corresponding risk among younger women was just three times greater.

The study has some key shortcomings. The researchers relied on the women's own assessment of their sleep problems and fibromyalgia symptoms, as opposed to official diagnoses. And though they took several potentially mitigating factors (such as body mass index, depression, and education levels) into account, they lacked data on anxiety, which has been linked to both sleep problems and fibromyalgia.
Other important factors that weren't measured in the study include menopausal status and a history of physical or psychological trauma, says Carol A. Landis, a professor at the University of Washington School of Nursing, in Seattle. As many as 30 percent to 50 percent of women with fibromyalgia report a history of trauma, Landis says.
Still, "The weight of the evidence really supports the important role of sleep in fibromyalgia," Arnold says. "We don't always understand what the biological mechanisms are underlying that association between sleep and pain, but clearly there's an important connection."

Doctors and patients should be aware of this connection and should address sleep problems -- especially unrefreshing sleep -- to lower the risk of the patient developing chronic pain, Arnold says.
"Sleep problems should be taken seriously," Mork says. "In addition to being a risk factor for fibromyalgia, sleep problems are also associated with increased risk of other chronic diseases," such as heart disease, he adds. "Early detection and proper treatment may therefore reduce the risk of future chronic disease.

Monday, August 15, 2011

Uncontrolled pain a problem in Canada

Excessive drug controls and exaggerated fears about opioids are contributing to uncontrolled pain and suffering in Canada, the nation's top medical journal says.

"Few things in life are as intolerable and incomprehensible as chronic physical pain," says an editorial published this week in the Canadian Medical Association Journal.

"A signal meant to alert us to protect our tissues has run amok . . . in its clutches, we all become irritable, insomniac and anhedonic. It confronts all clinicians and challenges all areas of health care."

An estimated 500,000 Canadians ages 12 to 44, 38 per cent of seniors in long-term care facilities and 27 per cent of seniors living at home experience chronic pain, the journal says.

According to the authors, "experts agree that much can be done now with newer analgesics, nonpharmacologic techniques such as nerve blocks and physical therapies, as well as spiritual and supportive care."

But pain is under-treated in Canada, the journal says. Specialized pain clinics are mainly clustered in big city hospitals. In many areas of the country, especially rural and remote regions, services are sparse, limited or "non-existent," the journal says.

"Patchy" pain education in medical schools, excessive drug controls and regulations, doctors who fear disciplinary action if they prescribe narcotics, myths about addiction and old attitudes that pain is unavoidable and a normal part of aging are all contributing to the problem, the journal says.

"Although the potential for opioid addiction and abuse is real, it is frequently exaggerated. Moreover, this concern is not an acceptable excuse for failure to control chronic pain."

The editorial comes amid concerns among pain-management advocates and patient groups that tighter controls on the use of opioids could worsen the already widespread problem of poorly controlled pain and make it harder for legitimate pain patients to get the medicine they need.

Ontario is preparing to start tracking all prescriptions for narcotics and to start keeping personal health information in a provincial narcotics database in response to a rise in opioid-related overdoses and deaths.

According to the College of Physicians and Surgeons of Ontario's report released last September, Avoiding Abuse, Achieving a Balance: Tackling the Opioid Public Health Crisis, prescription opioids — which include oxycodone (the active ingredient in OxyContin), morphine, codeine and methadone — are more likely to be found on the street than heroin and are now "a street drug of choice for teens."
Between 1991 and 2009, the number of prescriptions in Ontario for oxycodone rose by 900 per cent. Meanwhile, the number of people seeking treatment for addiction to oxycodone is increasing. The college says deaths due to oxycodone increased to 119 in 2006 from 35 in 2002.

Canada is one of the highest consumers in the world of opioid medications.

Dr. Ken Flegel, senior associate editor of the CMAJ and an internal medicine doctor in Montreal, said the journal isn't arguing that abuse of OxyContin is not a problem.

"We're not not part of the cautionary movement here," Flegel told Postmedia News.

"There are many other narcotic choices, and there are many other choices short of using narcotics for chronic pain," he said.

But Flegel said the burden of chronic pain on individual lives "is way too costly and it's worth taking a risk on the habituation side." Flegel said the medical literature shows that the vast majority of people who take narcotics for chronic pain "aren't addicts. They just have chronic pain and all they want to do is be rid of the pain," he said. "And the day they're rid of the chronic pain they also want to be rid of the narcotics."

"We think that the urban myth in the profession that using narcotics for chronic pain is a bridge to becoming a drug addict is probably overblown," he said.

He and his co-authors argue for a broad strategy to improve chronic-pain care for Canadians, including increased pain management education and expertise, telemedicine networks connecting doctors in rural and remote regions with pain centres, and programs that help teach patients and families ways to cope with and reduce chronic pain.

One of the biggest barriers is attitudes inside the profession, Flegel says. Many doctors graduated before chronic, non-cancer pain was even taken seriously. The thinking was "it wasn't important," he says, that "the ones (patients) who have bad pain are cancer patients who are dying, and that's where you should focus, and surgical patients — of course everybody agrees they shouldn't have pain."

But Flegel said chronic pain is prevalent and leads to anxiety and depression, "and we all know depression itself is associated with strokes, heart attack and cancer.

"The profession needs to get more expert at this," he said. "Most people with chronic pain can have the chronic pain managed, and some of them can actually have it relieved."

He said awareness needs to be raised among the public that "there is help out there, if they keep looking, and if they get good at finding the help they can take ownership of the management of the pain, or their families can, and do a lot more about it than has been done about it now."

In Canada, the Canadian Pain Society and other groups are calling for a national pain strategy that would officially recognize chronic pain as a disease in its own right — not merely a symptom of something else. The strategy urges better co-ordination of resources, more undergraduate and graduate training in pain, better prevention and improved treatment across the country, including more multi-disciplinary pain clinics.

Severe chronic pain can affect every aspect of a person's life, "and it can lead people to really deciding to live no longer," says Dr. Mary Lynch, past president of the Canadian Pain Society and director of the pain management unit at Queen Elizabeth II Health Sciences Centre in Halifax. Studies suggest that people with chronic pain have at least twice the rate of suicide as people living without pain.

"We know that there's a huge problem out there about unaddressed pain . . . and all the emotional and mental suffering that goes with it," Lynch said.

If more isn't done to address it, "the rates of chronic pain are going to climb, the need for the use of stronger and stronger pain medications is going to climb and we're going to have an even bigger problem on our hands."

Thursday, August 4, 2011

Kern Board of Supervisors votes to end MM collectives

On July 22, 2011
The Kern County Board of Supervisors announced their recommendations:

Extending the moratorium prohibiting the opening 
of any new dispensaries
Prohibit Marijuana Cooperatives in
unincorporated areas in the County of Kern
Prohibit outdoor cultivation
Prohibit and outlaw edible Marijuana products
(Page 1) (Page 2) (Page 3) (Page 4) (Page 5) (Page 6)

Saturday, July 30, 2011

Problem with subscription by email element

I have become aware that the feature that lets people subscribe to my blog by email is not working.  After trying with feedburner to resolve this issue (unsuccessfully) I have decided to remove the feature from my blog.  I hope those of you will come back and become followers of the blog.  I am dreadfully sorry for any inconvenience this has caused.

Friday, July 29, 2011

Low Vitamin D Linked to Chronic Musculoskeletal Pain : Internal Medicine News

Low Vitamin D Linked to Chronic Musculoskeletal Pain : Internal Medicine News

Pain: The Universal Disorder

You know it at once. It may be the fiery sensation of a burn moments after your finger touches the stove. Or it's a dull ache above your brow after a day of stress and tension. Or you may recognize it as a sharp pierce in your back after you lift something heavy.

It is pain. In its most benign form, it warns us that something isn't quite right, that we should take medicine or see a doctor. At its worst, however, pain robs us of our productivity, our well-being, and, for many of us suffering from extended illness, our very lives. Pain is a complex perception that differs enormously among individual patients, even those who appear to have identical injuries or illnesses.

In 1931, the French medical missionary Dr. Albert Schweitzer wrote, "Pain is a more terrible lord of mankind than even death itself." Today, pain has become the universal disorder, a serious and costly public health issue, and a challenge for family, friends, and health care providers who must give support to the individual suffering from the physical as well as the emotional consequences of pain.

A Brief History of Pain

Ancient civilizations recorded on stone tablets accounts of pain and the treatments used: pressure, heat, water, and sun. Early humans related pain to evil, magic, and demons. Relief of pain was the responsibility of sorcerers, shamans, priests, and priestesses, who used herbs, rites, and ceremonies as their treatments.

The Greeks and Romans were the first to advance a theory of sensation, the idea that the brain and nervous system have a role in producing the perception of pain. But it was not until the Middle Ages and well into the Renaissance-the 1400s and 1500s-that evidence began to accumulate in support of these theories. Leonardo da Vinci and his contemporaries came to believe that the brain was the central organ responsible for sensation. Da Vinci also developed the idea that the spinal cord transmits sensations to the brain.

In the 17th and 18th centuries, the study of the body-and the senses-continued to be a source of wonder for the world's philosophers. In 1664, the French philosopher René Descartes described what to this day is still called a "pain pathway." Descartes illustrated how particles of fire, in contact with the foot, travel to the brain and he compared pain sensation to the ringing of a bell.

In the 19th century, pain came to dwell under a new domain-science-paving the way for advances in pain therapy. Physician-scientists discovered that opium, morphine, codeine, and cocaine could be used to treat pain. These drugs led to the development of aspirin, to this day the most commonly used pain reliever. Before long, anesthesia-both general and regional-was refined and applied during surgery.

"It has no future but itself," wrote the 19th century American poet Emily Dickinson, speaking about pain. As the 21st century unfolds, however, advances in pain research are creating a less grim future than that portrayed in Dickinson’s verse, a future that includes a better understanding of pain, along with greatly improved treatments to keep it in check.

The Two Faces of Pain: Acute and Chronic

What is pain? The International Association for the Study of Pain defines it as: An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.

It is useful to distinguish between two basic types of pain, acute and chronic, and they differ greatly.
  • Acute pain, for the most part, results from disease, inflammation, or injury to tissues. This type of pain generally comes on suddenly, for example, after trauma or surgery, and may be accompanied by anxiety or emotional distress. The cause of acute pain can usually be diagnosed and treated, and the pain is self-limiting, that is, it is confined to a given period of time and severity. In some rare instances, it can become chronic.
  • Chronic pain is widely believed to represent disease itself. It can be made much worse by environmental and psychological factors. Chronic pain persists over a longer period of time than acute pain and is resistant to most medical treatments. It can—and often does—cause severe problems for patients.  A person may have two or more co-existing chronic pain conditions.  Such conditions can include chronic fatigue syndrome, endometriosis, fibromyalgia, inflammatory bowel disease, interstitial cystitis, temporomandibular joint dysfunction, and vulvodynia.  It is not known whether these disorders share a common cause.

The A to Z of Pain

Hundreds of pain syndromes or disorders make up the spectrum of pain. There are the most benign, fleeting sensations of pain, such as a pin prick. There is the pain of childbirth, the pain of a heart attack, and the pain that sometimes follows amputation of a limb. There is also pain accompanying cancer and the pain that follows severe trauma, such as that associated with head and spinal cord injuries. A sampling of common pain syndromes follows, listed alphabetically.

Arachnoiditis is a condition in which one of the three membranes covering the brain and spinal cord, called the arachnoid membrane, becomes inflamed. A number of causes, including infection or trauma, can result in inflammation of this membrane. Arachnoiditis can produce disabling, progressive, and even permanent pain.

Arthritis. Millions of Americans suffer from arthritic conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and gout. These disorders are characterized by joint pain in the extremities. Many other inflammatory diseases affect the body's soft tissues, including tendonitis and bursitis.

Back pain has become the high price paid by our modern lifestyle and is a startlingly common cause of disability for many Americans, including both active and inactive people. Back pain that spreads to the leg is called sciatica and is a very common condition (see below). Another common type of back pain is associated with the discs of the spine, the soft, spongy padding between the vertebrae (bones) that form the spine. Discs protect the spine by absorbing shock, but they tend to degenerate over time and may sometimes rupture.

Spondylolisthesis is a back condition that occurs when one vertebra extends over another, causing pressure on nerves and therefore pain. Also, damage to nerve roots (see Spine Basics in the Appendix) is a serious condition, called radiculopathy, that can be extremely painful. Treatment for a damaged disc includes drugs such as painkillers, muscle relaxants, and steroids; exercise or rest, depending on the patient's condition; adequate support, such as a brace or better mattress and physical therapy. In some cases, surgery may be required to remove the damaged portion of the disc and return it to its previous condition, especially when it is pressing a nerve root. Surgical procedures include discectomy, laminectomy, or spinal fusion (see section on surgery in How is Pain Treated? for more information on these treatments).

Burn pain can be profound and poses an extreme challenge to the medical community. First-degree burns are the least severe; with third-degree burns, the skin is lost. Depending on the injury, pain accompanying burns can be excruciating, and even after the wound has healed patients may have chronic pain at the burn site.

Central pain syndrome-see "Trauma" below.

Cancer pain can accompany the growth of a tumor, the treatment of cancer, or chronic problems related to cancer's permanent effects on the body. Fortunately, most cancer pain can be treated to help minimize discomfort and stress to the patient.

Headaches affect millions of Americans. The three most common types of chronic headache are migraines, cluster headaches, and tension headaches. Each comes with its own telltale brand of pain.
  • Migraines are characterized by throbbing pain and sometimes by other symptoms, such as nausea and visual disturbances. Migraines are more frequent in women than men. Stress can trigger a migraine headache, and migraines can also put the sufferer at risk for stroke.
  • Cluster headaches are characterized by excruciating, piercing pain on one side of the head; they occur more frequently in men than women.
  • Tension headaches are often described as a tight band around the head.
Head and facial pain can be agonizing, whether it results from dental problems or from disorders such as cranial neuralgia, in which one of the nerves in the face, head, or neck is inflamed. Another condition,

trigeminal neuralgia (also called tic douloureux), affects the largest of the cranial nerves (see The Nervous Systems in the Appendix) and is characterized by a stabbing, shooting pain.

Muscle pain can range from an aching muscle, spasm, or strain, to the severe spasticity that accompanies paralysis. Another disabling syndrome is fibromyalgia, a disorder characterized by fatigue, stiffness, joint tenderness, and widespread muscle pain. Polymyositis, dermatomyositis, and inclusion body myositis are painful disorders characterized by muscle inflammation. They may be caused by infection or autoimmune dysfunction and are sometimes associated with connective tissue disorders, such as lupus and rheumatoid arthritis.

Myofascial pain syndromes affect sensitive areas known as trigger points, located within the body's muscles. Myofascial pain syndromes are sometimes misdiagnosed and can be debilitating. Fibromyalgia is a type of myofascial pain syndrome.

Neuropathic pain is a type of pain that can result from injury to nerves, either in the peripheral or central nervous system (see The Nervous Systems in the Appendix). Neuropathic pain can occur in any part of the body and is frequently described as a hot, burning sensation, which can be devastating to the affected individual. It can result from diseases that affect nerves (such as diabetes) or from trauma, or, because chemotherapy drugs can affect nerves, it can be a consequence of cancer treatment. Among the many neuropathic pain conditions are diabetic neuropathy (which results from nerve damage secondary to vascular problems that occur with diabetes); reflex sympathetic dystrophy syndrome (see below), which can follow injury; phantom limb and post-amputation pain (see Phantom Pain in the Appendix), which can result from the surgical removal of a limb; postherpetic neuralgia, which can occur after an outbreak of shingles; and central pain syndrome, which can result from trauma to the brain or spinal cord.

Reflex sympathetic dystrophy syndrome, or RSDS, is accompanied by burning pain and hypersensitivity to temperature. Often triggered by trauma or nerve damage, RSDS causes the skin of the affected area to become characteristically shiny. In recent years, RSDS has come to be called complex regional pain syndrome (CRPS); in the past it was often called causalgia.

Repetitive stress injuries are muscular conditions that result from repeated motions performed in the course of normal work or other daily activities. They include:
  • writer's cramp, which affects musicians and writers and others,
  • compression or entrapment neuropathies, including carpal tunnel syndrome, caused by chronic overextension of the wrist and
  • tendonitis or tenosynovitis, affecting one or more tendons.
Sciatica is a painful condition caused by pressure on the sciatic nerve, the main nerve that branches off the spinal cord and continues down into the thighs, legs, ankles, and feet. Sciatica is characterized by pain in the buttocks and can be caused by a number of factors. Exertion, obesity, and poor posture can all cause pressure on the sciatic nerve. One common cause of sciatica is a herniated disc (see Spine Basics in the Appendix).

Shingles and other painful disorders affect the skin. Pain is a common symptom of many skin disorders, even the most common rashes. One of the most vexing neurological disorders is shingles or herpes zoster, an infection that often causes agonizing pain resistant to treatment. Prompt treatment with antiviral agents is important to arrest the infection, which if prolonged can result in an associated condition known as postherpetic neuralgia. Other painful disorders affecting the skin include:
  • vasculitis, or inflammation of blood vessels;
  • other infections, including herpes simplex;
  • skin tumors and cysts, and
  • tumors associated with neurofibromatosis, a neurogenetic disorder.
Sports injuries are common. Sprains, strains, bruises, dislocations, and fractures are all well-known words in the language of sports. Pain is another. In extreme cases, sports injuries can take the form of costly and painful spinal cord and head injuries, which cause severe suffering and disability.

Spinal stenosis refers to a narrowing of the canal surrounding the spinal cord. The condition occurs naturally with aging. Spinal stenosis causes weakness in the legs and leg pain usually felt while the person is standing up and often relieved by sitting down.

Surgical pain may require regional or general anesthesia during the procedure and medications to control discomfort following the operation. Control of pain associated with surgery includes presurgical preparation and careful monitoring of the patient during and after the procedure.

Temporomandibular disorders are conditions in which the temporomandibular joint (the jaw) is damaged and/or the muscles used for chewing and talking become stressed, causing pain. The condition may be the result of a number of factors, such as an injury to the jaw or joint misalignment, and may give rise to a variety of symptoms, most commonly pain in the jaw, face, and/or neck muscles. Physicians reach a diagnosis by listening to the patient's description of the symptoms and by performing a simple examination of the facial muscles and the temporomandibular joint.

Trauma can occur after injuries in the home, at the workplace, during sports activities, or on the road. Any of these injuries can result in severe disability and pain. Some patients who have had an injury to the spinal cord experience intense pain ranging from tingling to burning and, commonly, both. Such patients are sensitive to hot and cold temperatures and touch. For these individuals, a touch can be perceived as intense burning, indicating abnormal signals relayed to and from the brain. This condition is called central pain syndrome or, if the damage is in the thalamus (the brain's center for processing bodily sensations), thalamic pain syndrome. It affects as many as 100,000 Americans with multiple sclerosis, Parkinson's disease, amputated limbs, spinal cord injuries, and stroke. Their pain is severe and is extremely difficult to treat effectively. A variety of medications, including analgesics, antidepressants, anticonvulsants, and electrical stimulation, are options available to central pain patients.

Vascular disease or injury-such as vasculitis or inflammation of blood vessels, coronary artery disease, and circulatory problems-all have the potential to cause pain. Vascular pain affects millions of Americans and occurs when communication between blood vessels and nerves is interrupted. Ruptures, spasms, constriction, or obstruction of blood vessels, as well as a condition called ischemia in which blood supply to organs, tissues, or limbs is cut off, can also result in pain.

How is Pain Diagnosed?

There is no way to tell how much pain a person has. No test can measure the intensity of pain, no imaging device can show pain, and no instrument can locate pain precisely. Sometimes, as in the case of headaches, physicians find that the best aid to diagnosis is the patient's own description of the type, duration, and location of pain. Defining pain as sharp or dull, constant or intermittent, burning or aching may give the best clues to the cause of pain. These descriptions are part of what is called the pain history, taken by the physician during the preliminary examination of a patient with pain.

Physicians, however, do have a number of technologies they use to find the cause of pain. Primarily these include:
  • Electrodiagnostic procedures include electromyography (EMG), nerve conduction studies, and evoked potential (EP) studies. Information from EMG can help physicians tell precisely which muscles or nerves are affected by weakness or pain. Thin needles are inserted in muscles and a physician can see or listen to electrical signals displayed on an EMG machine. With nerve conduction studies the doctor uses two sets of electrodes (similar to those used during an electrocardiogram) that are placed on the skin over the muscles. The first set gives the patient a mild shock that stimulates the nerve that runs to that muscle. The second set of electrodes is used to make a recording of the nerve's electrical signals, and from this information the doctor can determine if there is nerve damage. EP tests also involve two sets of electrodes-one set for stimulating a nerve (these electrodes are attached to a limb) and another set on the scalp for recording the speed of nerve signal transmission to the brain.
  • Imaging, especially magnetic resonance imaging or MRI, provides physicians with pictures of the body's structures and tissues. MRI uses magnetic fields and radio waves to differentiate between healthy and diseased tissue.
  • A neurological examination in which the physician tests movement, reflexes, sensation, balance, and coordination.
  • X-rays produce pictures of the body's structures, such as bones and joints.

How is Pain Treated?

The goal of pain management is to improve function, enabling individuals to work, attend school, or participate in other day-to-day activities. Patients and their physicians have a number of options for the treatment of pain; some are more effective than others. Sometimes, relaxation and the use of imagery as a distraction provide relief. These methods can be powerful and effective, according to those who advocate their use. Whatever the treatment regime, it is important to remember that pain is treatable. The following treatments are among the most common.

Acetaminophen is the basic ingredient found in Tylenol® and its many generic equivalents. It is sold over the counter, in a prescription-strength preparation, and in combination with codeine (also by prescription).

Acupuncture dates back 2,500 years and involves the application of needles to precise points on the body. It is part of a general category of healing called traditional Chinese or Oriental medicine. Acupuncture remains controversial but is quite popular and may one day prove to be useful for a variety of conditions as it continues to be explored by practitioners, patients, and investigators.

Analgesic refers to the class of drugs that includes most painkillers, such as aspirin, acetaminophen, and ibuprofen. The word analgesic is derived from ancient Greek and means to reduce or stop pain. Nonprescription or over-the-counter pain relievers are generally used for mild to moderate pain. Prescription pain relievers, sold through a pharmacy under the direction of a physician, are used for more moderate to severe pain.

Anticonvulsants are used for the treatment of seizure disorders but are also sometimes prescribed for the treatment of pain. Carbamazepine in particular is used to treat a number of painful conditions, including trigeminal neuralgia. Another antiepileptic drug, gabapentin, is being studied for its pain-relieving properties, especially as a treatment for neuropathic pain.

Antidepressants are sometimes used for the treatment of pain and, along with neuroleptics and lithium, belong to a category of drugs called psychotropic drugs. In addition, anti-anxiety drugs called benzodiazepines also act as muscle relaxants and are sometimes used as pain relievers. Physicians usually try to treat the condition with analgesics before prescribing these drugs.

Antimigraine drugs include the triptans- sumatriptan (Imitrex®), naratriptan (Amerge®), and zolmitriptan (Zomig®)-and are used specifically for migraine headaches. They can have serious side effects in some people and therefore, as with all prescription medicines, should be used only under a doctor's care.
Aspirin may be the most widely used pain-relief agent and has been sold over the counter since 1905 as a treatment for fever, headache, and muscle soreness.

Biofeedback is used for the treatment of many common pain problems, most notably headache and back pain. Using a special electronic machine, the patient is trained to become aware of, to follow, and to gain control over certain bodily functions, including muscle tension, heart rate, and skin temperature. The individual can then learn to effect a change in his or her responses to pain, for example, by using relaxation techniques. Biofeedback is often used in combination with other treatment methods, generally without side effects. Similarly, the use of relaxation techniques in the treatment of pain can increase the patient's feeling of well-being.

Capsaicin is a chemical found in chili peppers that is also a primary ingredient in pain-relieving creams (see Chili Peppers, Capsaicin, and Pain in the Appendix).

Chemonucleolysis is a treatment in which an enzyme, chymopapain, is injected directly into a herniated lumbar disc (see Spine Basics in the Appendix) in an effort to dissolve material around the disc, thus reducing pressure and pain. The procedure's use is extremely limited, in part because some patients may have a life-threatening allergic reaction to chymopapain.

Chiropractic care may ease back pain, neck pain, headaches, and musculoskeletal conditions.  It involves "hands-on" therapy designed to adjust the relationship between the body's structure (mainly the spine) and its functioning.  Chiropractic spinal manipulation includes the adjustment and manipulation of the joints and adjacent tissues.  Such care may also involve therapeutic and rehabilitative exercises.

Cognitive-behavioral therapy involves a wide variety of coping skills and relaxation methods to help prepare for and cope with pain. It is used for postoperative pain, cancer pain, and the pain of childbirth.

Counseling can give a patient suffering from pain much needed support, whether it is derived from family, group, or individual counseling. Support groups can provide an important adjunct to drug or surgical treatment. Psychological treatment can also help patients learn about the physiological changes produced by pain.

COX-2 inhibitors may be effective for individuals with arthritis. For many years scientists have wanted to develop a drug that works as well as morphine but without its negative side effects. Nonsteroidal anti-inflammatory drugs (NSAIDs) work by blocking two enzymes, cyclooxygenase-1 and cyclooxygenase-2, both of which promote production of hormones called prostaglandins, which in turn cause inflammation, fever, and pain. The newer COX-2 inhibitors primarily block cyclooxygenase-2 and are less likely to have the gastrointestinal side effects sometimes produced by NSAIDs.

In 1999, the Food and Drug Administration approved a COX-2 inhibitor-celecoxib-for use in cases of chronic pain. The long-term effects of all COX-2 inhibitors are still being evaluated, especially in light of new information suggesting that these drugs may increase the risk of heart attack and stroke. Patients taking any of the COX-2 inhibitors should review their drug treatment with their doctors.

Electrical stimulation, including transcutaneous electrical stimulation (TENS), implanted electric nerve stimulation, and deep brain or spinal cord stimulation, is the modern-day extension of age-old practices in which the nerves of muscles are subjected to a variety of stimuli, including heat or massage. Electrical stimulation, no matter what form, involves a major surgical procedure and is not for everyone, nor is it 100 percent effective. The following techniques each require specialized equipment and personnel trained in the specific procedure being used:
  • TENS uses tiny electrical pulses, delivered through the skin to nerve fibers, to cause changes in muscles, such as numbness or contractions. This in turn produces temporary pain relief. There is also evidence that TENS can activate subsets of peripheral nerve fibers that can block pain transmission at the spinal cord level, in much the same way that shaking your hand can reduce pain.
  • Peripheral nerve stimulation uses electrodes placed surgically on a carefully selected area of the body. The patient is then able to deliver an electrical current as needed to the affected area, using an antenna and transmitter.
  • Spinal cord stimulation uses electrodes surgically inserted within the epidural space of the spinal cord. The patient is able to deliver a pulse of electricity to the spinal cord using a small box-like receiver and an antenna taped to the skin.
  • Deep brain or intracerebral stimulation is considered an extreme treatment and involves surgical stimulation of the brain, usually the thalamus. It is used for a limited number of conditions, including severe pain, central pain syndrome, cancer pain, phantom limb pain, and other neuropathic pains.
Exercise has come to be a prescribed part of some doctors' treatment regimes for patients with pain. Because there is a known link between many types of chronic pain and tense, weak muscles, exercise-even light to moderate exercise such as walking or swimming-can contribute to an overall sense of well-being by improving blood and oxygen flow to muscles. Just as we know that stress contributes to pain, we also know that exercise, sleep, and relaxation can all help reduce stress, thereby helping to alleviate pain. Exercise has been proven to help many people with low back pain. It is important, however, that patients carefully follow the routine laid out by their physicians.

Hypnosis, first approved for medical use by the American Medical Association in 1958, continues to grow in popularity, especially as an adjunct to pain medication. In general, hypnosis is used to control physical function or response, that is, the amount of pain an individual can withstand. How hypnosis works is not fully understood. Some believe that hypnosis delivers the patient into a trance-like state, while others feel that the individual is simply better able to concentrate and relax or is more responsive to suggestion. Hypnosis may result in relief of pain by acting on chemicals in the nervous system, slowing impulses. Whether and how hypnosis works involves greater insight-and research-into the mechanisms underlying human consciousness.

Ibuprofen is a member of the aspirin family of analgesics, the so-called nonsteroidal anti-inflammatory drugs (see below). It is sold over the counter and also comes in prescription-strength preparations.

Low-power lasers have been used occasionally by some physical therapists as a treatment for pain, but like many other treatments, this method is not without controversy.

Magnets are increasingly popular with athletes who swear by their effectiveness for the control of sports-related pain and other painful conditions. Usually worn as a collar or wristwatch, the use of magnets as a treatment dates back to the ancient Egyptians and Greeks. While it is often dismissed as quackery and pseudoscience by skeptics, proponents offer the theory that magnets may effect changes in cells or body chemistry, thus producing pain relief.

Narcotics (see Opioids, below).

Nerve blocks employ the use of drugs, chemical agents, or surgical techniques to interrupt the relay of pain messages between specific areas of the body and the brain. There are many different names for the procedure, depending on the technique or agent used. Types of surgical nerve blocks include neurectomy; spinal dorsal, cranial, and trigeminal rhizotomy; and sympathectomy, also called sympathetic blockade (see Nerve Blocks in the Appendix).

Nonsteroidal anti-inflammatory drugs (NSAIDs) (including aspirin and ibuprofen) are widely prescribed and sometimes called non-narcotic or non-opioid analgesics. They work by reducing inflammatory responses in tissues. Many of these drugs irritate the stomach and for that reason are usually taken with food. Although acetaminophen may have some anti-inflammatory effects, it is generally distinguished from the traditional NSAIDs.

Opioids are derived from the poppy plant and are among the oldest drugs known to humankind. They include codeine and perhaps the most well-known narcotic of all, morphine. Morphine can be administered in a variety of forms, including a pump for patient self-administration. Opioids have a narcotic effect, that is, they induce sedation as well as pain relief, and some patients may become physically dependent upon them. For these reasons, patients given opioids should be monitored carefully; in some cases stimulants may be prescribed to counteract the sedative side effects. In addition to drowsiness, other common side effects include constipation, nausea, and vomiting.

Physical therapy and rehabilitation date back to the ancient practice of using physical techniques and methods, such as heat, cold, exercise, massage, and manipulation, in the treatment of certain conditions. These may be applied to increase function, control pain, and speed the patient toward full recovery.

Placebos offer some individuals pain relief although whether and how they have an effect is mysterious and somewhat controversial. Placebos are inactive substances, such as sugar pills, or harmless procedures, such as saline injections or sham surgeries, generally used in clinical studies as control factors to help determine the efficacy of active treatments. Although placebos have no direct effect on the underlying causes of pain, evidence from clinical studies suggests that many pain conditions such as migraine headache, back pain, post-surgical pain, rheumatoid arthritis, angina, and depression sometimes respond well to them. This positive response is known as the placebo effect, which is defined as the observable or measurable change that can occur in patients after administration of a placebo. Some experts believe the effect is psychological and that placebos work because the patients believe or expect them to work. Others say placebos relieve pain by stimulating the brain's own analgesics and setting the body's self-healing forces in motion. A third theory suggests that the act of taking placebos relieves stress and anxiety-which are known to aggravate some painful conditions-and, thus, cause the patients to feel better. Still, placebos are considered controversial because by definition they are inactive and have no actual curative value.

R.I.C.E.-Rest, Ice, Compression, and Elevation-are four components prescribed by many orthopedists, coaches, trainers, nurses, and other professionals for temporary muscle or joint conditions, such as sprains or strains. While many common orthopedic problems can be controlled with these four simple steps, especially when combined with over-the-counter pain relievers, more serious conditions may require surgery or physical therapy, including exercise, joint movement or manipulation, and stimulation of muscles.

Surgery, although not always an option, may be required to relieve pain, especially pain caused by back problems or serious musculoskeletal injuries. Surgery may take the form of a nerve block (see Nerve Blocks in the Appendix) or it may involve an operation to relieve pain from a ruptured disc. Surgical procedures for back problems include discectomy or, when microsurgical techniques are used, microdiscectomy, in which the entire disc is removed; laminectomy, a procedure in which a surgeon removes only a disc fragment, gaining access by entering through the arched portion of a vertebra; and spinal fusion, a procedure where the entire disc is removed and replaced with a bone graft. In a spinal fusion, the two vertebrae are then fused together. Although the operation can cause the spine to stiffen, resulting in lost flexibility, the procedure serves one critical purpose: protection of the spinal cord. Other operations for pain include rhizotomy, in which a nerve close to the spinal cord is cut, and cordotomy, where bundles of nerves within the spinal cord are severed. Cordotomy is generally used only for the pain of terminal cancer that does not respond to other therapies. Another operation for pain is the dorsal root entry zone operation, or DREZ, in which spinal neurons corresponding to the patient's pain are destroyed surgically. Because surgery can result in scar tissue formation that may cause additional problems, patients are well advised to seek a second opinion before proceeding. Occasionally, surgery is carried out with electrodes that selectively damage neurons in a targeted area of the brain. These procedures rarely result in long-term pain relief, but both physician and patient may decide that the surgical procedure will be effective enough that it justifies the expense and risk. In some cases, the results of an operation are remarkable. For example, many individuals suffering from trigeminal neuralgia who are not responsive to drug treatment have had great success with a procedure called microvascular decompression, in which tiny blood vessels are surgically separated from surrounding nerves.

What is the Role of Age and Gender in Pain?

Gender and Pain

It is now widely believed that pain affects men and women differently. While the sex hormones estrogen and testosterone certainly play a role in this phenomenon, psychology and culture, too, may account at least in part for differences in how men and women receive pain signals. For example, young children may learn to respond to pain based on how they are treated when they experience pain. Some children may be cuddled and comforted, while others may be encouraged to tough it out and to dismiss their pain.

Many investigators are turning their attention to the study of gender differences and pain. Women, many experts now agree, recover more quickly from pain, seek help more quickly for their pain, and are less likely to allow pain to control their lives. They also are more likely to marshal a variety of resources-coping skills, support, and distraction-with which to deal with their pain.

Research in this area is yielding fascinating results. For example, male experimental animals injected with estrogen, a female sex hormone, appear to have a lower tolerance for pain-that is, the addition of estrogen appears to lower the pain threshold. Similarly, the presence of testosterone, a male hormone, appears to elevate tolerance for pain in female mice: the animals are simply able to withstand pain better. Female mice deprived of estrogen during experiments react to stress similarly to male animals. Estrogen, therefore, may act as a sort of pain switch, turning on the ability to recognize pain.

Investigators know that males and females both have strong natural pain-killing systems, but these systems operate differently. For example, a class of painkillers called kappa-opioids is named after one of several opioid receptors to which they bind, the kappa-opioid receptor, and they include the compounds nalbuphine (Nubain®) and butorphanol (Stadol®). Research suggests that kappa-opioids provide better pain relief in women.

Though not prescribed widely, kappa-opioids are currently used for relief of labor pain and in general work best for short-term pain. Investigators are not certain why kappa-opioids work better in women than men. Is it because a woman's estrogen makes them work, or because a man's testosterone prevents them from working? Or is there another explanation, such as differences between men and women in their perception of pain? Continued research may result in a better understanding of how pain affects women differently from men, enabling new and better pain medications to be designed with gender in mind.

Pain in Aging and Pediatric Populations: Special Needs and Concerns

Pain is the number one complaint of older Americans, and one in five older Americans takes a painkiller regularly. In 1998, the American Geriatrics Society (AGS) issued guidelines* for the management of pain in older people. The AGS panel addressed the incorporation of several non-drug approaches in patients' treatment plans, including exercise. AGS panel members recommend that, whenever possible, patients use alternatives to aspirin, ibuprofen, and other NSAIDs because of the drugs' side effects, including stomach irritation and gastrointestinal bleeding. For older adults, acetaminophen is the first-line treatment for mild-to-moderate pain, according to the guidelines. More serious chronic pain conditions may require opioid drugs (narcotics), including codeine or morphine, for relief of pain.

Pain in younger patients also requires special attention, particularly because young children are not always able to describe the degree of pain they are experiencing. Although treating pain in pediatric patients poses a special challenge to physicians and parents alike, pediatric patients should never be undertreated. Recently, special tools for measuring pain in children have been developed that, when combined with cues used by parents, help physicians select the most effective treatments.

Nonsteroidal agents, and especially acetaminophen, are most often prescribed for control of pain in children. In the case of severe pain or pain following surgery, acetaminophen may be combined with codeine.
* Journal of the American Geriatrics Society (1998; 46:635-651).

A Pain Primer: What Do We Know About Pain?

We may experience pain as a prick, tingle, sting, burn, or ache. Receptors on the skin trigger a series of events, beginning with an electrical impulse that travels from the skin to the spinal cord. The spinal cord acts as a sort of relay center where the pain signal can be blocked, enhanced, or otherwise modified before it is relayed to the brain. One area of the spinal cord in particular, called the dorsal horn (see section on Spine Basics in the Appendix), is important in the reception of pain signals.

The most common destination in the brain for pain signals is the thalamus and from there to the cortex, the headquarters for complex thoughts. The thalamus also serves as the brain's storage area for images of the body and plays a key role in relaying messages between the brain and various parts of the body. In people who undergo an amputation, the representation of the amputated limb is stored in the thalamus. (For a discussion of the thalamus and its role in this phenomenon, called phantom pain, see section on Phantom Pain in the Appendix.)

Pain is a complicated process that involves an intricate interplay between a number of important chemicals found naturally in the brain and spinal cord. In general, these chemicals, called neurotransmitters, transmit nerve impulses from one cell to another.

There are many different neurotransmitters in the human body; some play a role in human disease and, in the case of pain, act in various combinations to produce painful sensations in the body. Some chemicals govern mild pain sensations; others control intense or severe pain.

The body's chemicals act in the transmission of pain messages by stimulating neurotransmitter receptors found on the surface of cells; each receptor has a corresponding neurotransmitter. Receptors function much like gates or ports and enable pain messages to pass through and on to neighboring cells. One brain chemical of special interest to neuroscientists is glutamate. During experiments, mice with blocked glutamate receptors show a reduction in their responses to pain. Other important receptors in pain transmission are opiate-like receptors. Morphine and other opioid drugs work by locking on to these opioid receptors, switching on pain-inhibiting pathways or circuits, and thereby blocking pain.

Another type of receptor that responds to painful stimuli is called a nociceptor. Nociceptors are thin nerve fibers in the skin, muscle, and other body tissues, that, when stimulated, carry pain signals to the spinal cord and brain. Normally, nociceptors only respond to strong stimuli such as a pinch. However, when tissues become injured or inflamed, as with a sunburn or infection, they release chemicals that make nociceptors much more sensitive and cause them to transmit pain signals in response to even gentle stimuli such as breeze or a caress. This condition is called allodynia -a state in which pain is produced by innocuous stimuli.
The body's natural painkillers may yet prove to be the most promising pain relievers, pointing to one of the most important new avenues in drug development. The brain may signal the release of painkillers found in the spinal cord, including serotonin, norepinephrine, and opioid-like chemicals. Many pharmaceutical companies are working to synthesize these substances in laboratories as future medications.

Endorphins and enkephalins are other natural painkillers. Endorphins may be responsible for the "feel good" effects experienced by many people after rigorous exercise; they are also implicated in the pleasurable effects of smoking.

Similarly, peptides, compounds that make up proteins in the body, play a role in pain responses. Mice bred experimentally to lack a gene for two peptides called tachykinins-neurokinin A and substance P-have a reduced response to severe pain. When exposed to mild pain, these mice react in the same way as mice that carry the missing gene. But when exposed to more severe pain, the mice exhibit a reduced pain response. This suggests that the two peptides are involved in the production of pain sensations, especially moderate-to-severe pain. Continued research on tachykinins, conducted with support from the NINDS, may pave the way for drugs tailored to treat different severities of pain.

Scientists are working to develop potent pain-killing drugs that act on receptors for the chemical acetylcholine. For example, a type of frog native to Ecuador has been found to have a chemical in its skin called epibatidine, derived from the frog's scientific name, Epipedobates tricolor. Although highly toxic, epibatidine is a potent analgesic and, surprisingly, resembles the chemical nicotine found in cigarettes. Also under development are other less toxic compounds that act on acetylcholine receptors and may prove to be more potent than morphine but without its addictive properties.

The idea of using receptors as gateways for pain drugs is a novel idea, supported by experiments involving substance P. Investigators have been able to isolate a tiny population of neurons, located in the spinal cord, that together form a major portion of the pathway responsible for carrying persistent pain signals to the brain. When animals were given injections of a lethal cocktail containing substance P linked to the chemical saporin, this group of cells, whose sole function is to communicate pain, were killed. Receptors for substance P served as a portal or point of entry for the compound. Within days of the injections, the targeted neurons, located in the outer layer of the spinal cord along its entire length, absorbed the compound and were neutralized. The animals' behavior was completely normal; they no longer exhibited signs of pain following injury or had an exaggerated pain response. Importantly, the animals still responded to acute, that is, normal, pain. This is a critical finding as it is important to retain the body's ability to detect potentially injurious stimuli. The protective, early warning signal that pain provides is essential for normal functioning. If this work can be translated clinically, humans might be able to benefit from similar compounds introduced, for example, through lumbar (spinal) puncture.

Another promising area of research using the body's natural pain-killing abilities is the transplantation of chromaffin cells into the spinal cords of animals bred experimentally to develop arthritis. Chromaffin cells produce several of the body's pain-killing substances and are part of the adrenal medulla, which sits on top of the kidney. Within a week or so, rats receiving these transplants cease to exhibit telltale signs of pain. Scientists, working with support from the NINDS, believe the transplants help the animals recover from pain-related cellular damage. Extensive animal studies will be required to learn if this technique might be of value to humans with severe pain.

One way to control pain outside of the brain, that is, peripherally, is by inhibiting hormones called prostaglandins. Prostaglandins stimulate nerves at the site of injury and cause inflammation and fever. Certain drugs, including NSAIDs, act against such hormones by blocking the enzyme that is required for their synthesis.

Blood vessel walls stretch or dilate during a migraine attack and it is thought that serotonin plays a complicated role in this process. For example, before a migraine headache, serotonin levels fall. Drugs for migraine include the triptans: sumatriptan (Imitrix®), naratriptan (Amerge®), and zolmitriptan (Zomig®). They are called serotonin agonists because they mimic the action of endogenous (natural) serotonin and bind to specific subtypes of serotonin receptors.

Ongoing pain research, much of it supported by the NINDS, continues to reveal at an unprecedented pace fascinating insights into how genetics, the immune system, and the skin contribute to pain responses.
The explosion of knowledge about human genetics is helping scientists who work in the field of drug development. We know, for example, that the pain-killing properties of codeine rely heavily on a liver enzyme, CYP2D6, which helps convert codeine into morphine. A small number of people genetically lack the enzyme CYP2D6; when given codeine, these individuals do not get pain relief. CYP2D6 also helps break down certain other drugs. People who genetically lack CYP2D6 may not be able to cleanse their systems of these drugs and may be vulnerable to drug toxicity. CYP2D6 is currently under investigation for its role in pain.

In his research, the late John C. Liebeskind, a renowned pain expert and a professor of psychology at UCLA, found that pain can kill by delaying healing and causing cancer to spread. In his pioneering research on the immune system and pain, Dr. Liebeskind studied the effects of stress-such as surgery-on the immune system and in particular on cells called natural killer or NK cells. These cells are thought to help protect the body against tumors. In one study conducted with rats, Dr. Liebeskind found that, following experimental surgery, NK cell activity was suppressed, causing the cancer to spread more rapidly. When the animals were treated with morphine, however, they were able to avoid this reaction to stress.

The link between the nervous and immune systems is an important one. Cytokines, a type of protein found in the nervous system, are also part of the body's immune system, the body's shield for fighting off disease. Cytokines can trigger pain by promoting inflammation, even in the absence of injury or damage. Certain types of cytokines have been linked to nervous system injury. After trauma, cytokine levels rise in the brain and spinal cord and at the site in the peripheral nervous system where the injury occurred. Improvements in our understanding of the precise role of cytokines in producing pain, especially pain resulting from injury, may lead to new classes of drugs that can block the action of these substances.

What is the Future of Pain Research?

In the forefront of pain research are scientists supported by the National Institutes of Health (NIH), including the NINDS. Other institutes at NIH that support pain research include the National Institute of Dental and Craniofacial Research, the National Cancer Institute, the National Institute of Nursing Research, the National Institute on Drug Abuse, and the National Institute of Mental Health. Developing better pain treatments is the primary goal of all pain research being conducted by these institutes.

Some pain medications dull the patient's perception of pain. Morphine is one such drug. It works through the body's natural pain-killing machinery, preventing pain messages from reaching the brain. Scientists are working toward the development of a morphine-like drug that will have the pain-deadening qualities of morphine but without the drug's negative side effects, such as sedation and the potential for addiction. Patients receiving morphine also face the problem of morphine tolerance, meaning that over time they require higher doses of the drug to achieve the same pain relief. Studies have identified factors that contribute to the development of tolerance; continued progress in this line of research should eventually allow patients to take lower doses of morphine.

One objective of investigators working to develop the future generation of pain medications is to take full advantage of the body's pain "switching center" by formulating compounds that will prevent pain signals from being amplified or stop them altogether. Blocking or interrupting pain signals, especially when there is no injury or trauma to tissue, is an important goal in the development of pain medications. An increased understanding of the basic mechanisms of pain will have profound implications for the development of future medicines. The following areas of research are bringing us closer to an ideal pain drug.

Systems and Imaging: The idea of mapping cognitive functions to precise areas of the brain dates back to phrenology, the now archaic practice of studying bumps on the head. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and other imaging technologies offer a vivid picture of what is happening in the brain as it processes pain. Using imaging, investigators can now see that pain activates at least three or four key areas of the brain's cortex-the layer of tissue that covers the brain. Interestingly, when patients undergo hypnosis so that the unpleasantness of a painful stimulus is not experienced, activity in some, but not all, brain areas is reduced. This emphasizes that the experience of pain involves a strong emotional component as well as the sensory experience, namely the intensity of the stimulus.

Channels: The frontier in the search for new drug targets is represented by channels. Channels are gate-like passages found along the membranes of cells that allow electrically charged chemical particles called ions to pass into the cells. Ion channels are important for transmitting signals through the nerve's membrane. The possibility now exists for developing new classes of drugs, including pain cocktails that would act at the site of channel activity.

Trophic Factors: A class of "rescuer" or "restorer" drugs may emerge from our growing knowledge of trophic factors, natural chemical substances found in the human body that affect the survival and function of cells. Trophic factors also promote cell death, but little is known about how something beneficial can become harmful. Investigators have observed that an over-accumulation of certain trophic factors in the nerve cells of animals results in heightened pain sensitivity, and that some receptors found on cells respond to trophic factors and interact with each other. These receptors may provide targets for new pain therapies.

Molecular Genetics: Certain genetic mutations can change pain sensitivity and behavioral responses to pain. People born genetically insensate to pain-that is, individuals who cannot feel pain-have a mutation in part of a gene that plays a role in cell survival. Using "knockout" animal models-animals genetically engineered to lack a certain gene-scientists are able to visualize how mutations in genes cause animals to become anxious, make noise, rear, freeze, or become hypervigilant. These genetic mutations cause a disruption or alteration in the processing of pain information as it leaves the spinal cord and travels to the brain. Knockout animals can be used to complement efforts aimed at developing new drugs.

Plasticity: Following injury, the nervous system undergoes a tremendous reorganization. This phenomenon is known as plasticity. For example, the spinal cord is "rewired" following trauma as nerve cell axons make new contacts, a phenomenon known as "sprouting." This in turn disrupts the cells' supply of trophic factors.

Scientists can now identify and study the changes that occur during the processing of pain. For example, using a technique called polymerase chain reaction, abbreviated PCR, scientists can study the genes that are induced by injury and persistent pain. There is evidence that the proteins that are ultimately synthesized by these genes may be targets for new therapies. The dramatic changes that occur with injury and persistent pain underscore that chronic pain should be considered a disease of the nervous system, not just prolonged acute pain or a symptom of an injury. Thus, scientists hope that therapies directed at preventing the long-term changes that occur in the nervous system will prevent the development of chronic pain conditions.

Neurotransmitters: Just as mutations in genes may affect behavior, they may also affect a number of neurotransmitters involved in the control of pain. Using sophisticated imaging technologies, investigators can now visualize what is happening chemically in the spinal cord. From this work, new therapies may emerge, therapies that can help reduce or obliterate severe or chronic pain.

Hope for the Future

Thousands of years ago, ancient peoples attributed pain to spirits and treated it with mysticism and incantations. Over the centuries, science has provided us with a remarkable ability to understand and control pain with medications, surgery, and other treatments. Today, scientists understand a great deal about the causes and mechanisms of pain, and research has produced dramatic improvements in the diagnosis and treatment of a number of painful disorders. For people who fight every day against the limitations imposed by pain, the work of NINDS-supported scientists holds the promise of an even greater understanding of pain in the coming years. Their research offers a powerful weapon in the battle to prolong and improve the lives of people with pain: hope.

 Where can I get more information?For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:

P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424