Tuesday, March 30, 2010

NIH Pain Consortium

The NIH Pain Consortium was established to enhance pain research and promote collaboration among researchers across the many NIH Institutes and Centers that have programs and activities addressing pain. To this end, the following goals have been identified for the Pain Consortium:

  • To develop a comprehensive and forward-thinking pain research agenda for the NIH - one that builds on what we have learned from our past efforts.

  • To identify key opportunities in pain research, particularly those that provide for multidisciplinary and trans-NIH participation.

  • To increase visibility for pain research - both within the NIH intramural and extramural communities, as well as outside the NIH. The latter audiences include our various pain advocacy and patient groups who have expressed their interests through scientific and legislative channels.

  • To pursue the pain research agenda through Public-Private partnerships, wherever applicable. This underscores a key dynamic that has been reinforced and encouraged through the Roadmap process.


Symptom Research: Methods and Opportunities (Max and Lynn, NIH) - An interactive textbook


Tuesday, March 16, 2010

We feel your pain: Extreme empaths - New Scientist

Horror films are simply a disconcerting watch for the majority of us, but for Jane Barrett they are literally torturous. She writhes in agony whenever the actors on the screen feel pain. "When I see violence in films I have an extreme reaction," she says. "I simply have to close my eyes. I start to feel nauseous and have to breathe deeply."

She is just one of many people who suffer from a range of disorders that give rise to "extreme empathy". Some of these people, like Barrett, empathise so strongly with others that they experience the same physical feelings - whether it's the tickle of a feather or the cut of a knife. Others, who suffer from a disorder known as echopraxia, just can't help immediately imitating the actions of others, even in inappropriate situations.

Far from being mere curiosities, understanding these conditions could have many pay-offs for neuroscience, such as illuminating conditions like phantom pain. They may even help answer the age-old question of whether empathy really is linked to compassion.

There is a general consensus that empathy-linked conditions arise from abnormalities in the common mechanisms for empathy found in all humans: although few of us experience sensations as powerful as Barrett's, we all wince at a brutal foul on the football field and feel compassion for someone experiencing grief. Many studies have suggested that our capacity for empathy arises from a specific group of neurons, labelled mirror neurons. First discovered in macaque monkeys, they are situated in and around the premotor cortex and parietal lobe - regions that span the top of the brain near the middle of the head. These neurons fire both when you perform an action and when you see someone else perform that action.

Although the challenges inherent in placing electrodes in people's brains have so far made it difficult to prove convincingly that individual neurons also act like this in humans, fMRI scans have supported the idea that certain populations of neurons do seem to behave in this mirroring fashion.

More ...


Monday, March 15, 2010

Discovery may bring cheaper pain relief - National Post

University of Calgary researchers say they've pinpointed the elusive genes of the opium poppy, a discovery that could lead to cheaper and more widespread painkillers.
The genes allow the poppy to produce some of the world's most widely used pain relievers: codeine and morphine, said University of Calgary biological sciences professor Peter Facchini. Enzymes encoded by the two genes have eluded scientists for at least 50 years, he said.
"These are the two that are unique in opium poppy that allow it uniquely among plants to make codeine and morphine," said Mr. Facchini.
The scientist has devoted 18 years to researching the opium poppy, and made the genetic discovery along with Jillian Hagel, a post-doctoral scientist in Mr. Facchini's lab.
Their findings, which were announced yesterday, will be published in a paper appearing in the online edition of Nature Chemical Biology.
Finding the gene responsible for a trait in an organism, such as knowing the gene for breast cancer or cystic fibrosis, is an important first step toward solving problems or using new technology, Mr. Facchini said.
The majority of codeine that is available pharmaceutically is produced by taking morphine from the plant and chemically converting it back to the codeine, he said.
With the poppy plant genetic discovery, scientists could potentially create plants that will stop production at codeine, eliminating some of the extra work around producing the painkiller, said Mr. Facchini.
"Being able to create a poppy variety that is blocked at codeine can reduce production costs," he said.
Ms. Hagel used high-tech genomics techniques to sort through up to 23,000 different genes on a single slide before zeroing in on codeine O-dementhylase, which produces the plant enzyme that converts codeine into morphine.
Dr. Facchini, who has filed a patent on the discovery, said one of the next steps is to use the codeine gene to create pharmaceuticals in yeast or bacteria--bypassing the plant altogether.
That research is still in its early stages, he said.
Codeine is the most common opiate in the world. About 80% of codeine and morphine in the world is consumed by six countries, including Canada, Facchini said. However, Canada imports all of its opiates from countries such as France or Australia that cultivate the opium poppy.
Canadians alone spends more than $100 million every year on codeine-containing pharmaceutical products.
The genetic discovery could potentially lower the costs of the drug, Dr. Facchini said.


Saturday, March 13, 2010

My Pain Diary - iPhone app

My Pain Diary was developed to eliminate some of the overhead in keeping a pain diary and communicating the information to health care professionals.

My Pain Diary has a unique story behind it in that the developer was diagnosed in 2008 with Type 1 CRPS.


Chronic Pain Tracker - iPhone app

Chronic Pain Tracker has been designed to improve the Patient-to-Doctor exchange of pain information.

Chronic Pain Tracker, the patient can monitor three key pain metrics:

· Pain Level - or the intensity of the pain

· Pain Location - where the pain is being experienced

· Pain Description - what the pain feels like

Sufferers of Chronic Pain know that each of these metrics can change day to day, or even hour to hour. This can make diagnosis and treatment of pain symptoms more challenging since patients most commonly describe their pain based on their most recent experience rather than using an evaluative process to statistically describe the typical pain symptoms being experienced.


Wednesday, March 10, 2010

Gene Linked To Pain Perception - Science News

One form of a common genetic variant may ratchet up pain sensitivity in people who have it, researchers report online March 8 in the Proceedings of the National Academy of Sciences.

The discovery could lead to more powerful pain treatments that lack the debilitating side effects of current drugs. "We could fill our clinics many times over with people with chronic pain that we can't help with our current medications," says neurologist and neuroscientist Stephen Waxman of Yale University School of Medicine and the Veterans Affairs Connecticut Hospital in West Haven.

In the new study, researchers led by clinical geneticist Geoffrey Woods of the Cambridge Institute for Medical Research in the United Kingdom examined the DNA of 578 people with the painful condition osteoarthritis. Woods and his colleagues searched for genetic variations that might be linked to how much pain a patient reported feeling — a subjective measure, Woods says, but currently the best researchers can do.

The team found that people who reported higher levels of pain were more likely to carry a particular DNA base, an A instead of a G, at a certain location in the gene SCN9A. The A version is found in an estimated 10 to 30 percent of people, Woods says, though its presence varies in populations of different ancestries.

This gene version may set the pain threshold, he says. "You're more sensitive to pain."

The same trend — higher pain levels reported by people who carried the A — held true in cohorts of people with other painful conditions including sciatica, phantom limb syndrome and lumbar discectomy. The A variant wasn't strongly associated with higher pain scores in patients with chronic pancreatitis, however. Woods says that might change as more people are added to the study.

The researchers also looked for the gene variant in 186 healthy women who had been assessed based on their responses to a number of painful stimuli. The women with the highest responses were more likely to have the A variant instead of the G.

The genetic variation affects the structure of a protein that sits on the outside of nerve cells and allows sodium to enter upon painful stimuli. The sodium influx then spurs the nerve cell to send a pain message to the brain.

This channel protein is a promising target for extremely specific and effective pain drugs, Waxman says: "Given that this channel has been indicted, it would be nice if we could develop therapeutic handles that turn it off or down."

Researchers already knew that people with mutations in SCN9A can have extreme pain syndromes. Genetic changes that render the protein completely inactive can leave a person impervious to pain, although otherwise healthy. Other mutations can lead to conditions such as "man on fire" syndrome, in which people experience relentless, searing pain.

Although these syndromes are extreme cases, they strongly implicate SCN9Aas important for pain thresholds, Waxman says. The new study is "an important paper that advances our understanding of pain."

In additional laboratory studies, the researchers found that nerve cells carrying the A variant of the gene took longer to close their sodium gates, allowing a stronger pain signal to be sent to the brain. Nerve cells carrying the more common G version of the gene snapped shut faster, stopping the pain signal sooner.


Monday, March 08, 2010

In the Face of Pain

In the Face of Pain Advocacy Toolkit provides you with a series of tools to advocate for people in pain. You can learn the basics of how to share messages about the rights of people in pain through your community, your local media outlets, your elected officials and your professional organizations.

You also have access to current data and statistics about condition or population-specific pain that can be used to support your advocacy efforts. Lastly, you have the capability to build a personalized advocacy plan, tailored to your specific interests.


Resource Guide for People with Pain

Partners Against Pain

Partners Against Pain® is a resource that serves patients, caregivers, and healthcare professionals to help alleviate unnecessary suffering by leading efforts to advance standards of pain care through education and advocacy

Partners Against Pain® offers people living with pain, their friends and families comprehensive and clear information on:

- Pain Assessment and Measurement 
- Pain Documentation 
- PainAdvocacy 
- Pain Resources, including the Patient Comfort Assessment Guide 
- Alternative Therapeutic Options


BBC News - Back pain 'eased by group therapy sessions'

A form of group "talking therapy" is a cheap, effective way to alleviate low back pain, a UK trial has shown.

The positive effect was still seen a year after the short six-session therapy programme, The Lancet reported.

The 600 patients taking part in the trial were also offered standard GP treatment including pain medication.

The sessions were designed to tackle "unhelpful" beliefs around back pain and physical activity and help patients better manage their condition.

Usually people with low back pain - one of the most common complaints GPs deal with - are advised to keep active, offered pain relief where needed and possibly other treatments such as acupuncture.

In the study, 400 people being treated in general practice were offered the six group therapy sessions and 200 people receiving standard care were monitored for a year.

The sessions - based loosely around a technique called cognitive behaviour therapy - were set up to discuss beliefs around doing physical activity and counter negative thoughts about back pain and its restrictions as well as relaxation techniques.

The one-and-a-half-hour sessions were also designed to help people overcome "fear" of hurting themselves more and how to get active again whilst avoiding flare-ups.

A year later, the people who underwent therapy scored significantly more highly on questionnaires designed to measure pain and disability.

Value for money

When looking at the costs, the team found the therapy was relatively cheap when the improvement in quality of life was taken into account, and better than the value for money offered by treatments such as acupuncture.

The researchers, from the Universities of Warwick and Oxford, said effective treatments that produced long-term results are "elusive" in low back pain.

Study author Zara Hansen, a clinical research fellow at the University of Warwick, said healthcare staff, including physiotherapists, psychotherapists and nurses, could learn how to run the course in a couple of days.

"The exciting bit here is that with a lot of back pain interventions, you'll get a feel-good factor and patients will feel better while they're undergoing the treatment but it's a short-term effect.

"But we showed they improve up to six months and then this is maintained for up to a year as they learn to manage their condition."

The team is looking at a project to roll out the programme to other areas of the country.

Dr Graham Davenport, clinical champion for musculoskeletal conditions at the Royal College of GPs, said chronic back pain was an extremely common condition and this sort of therapy could prove extremely useful.

"It's really just about changing people's beliefs.

"It's an excellent and very sensible treatment, the problem is the logistics of getting staff trained to deliver it but if we could overcome that it would be great."


Lack of optimal pain care delivery system costs more than $100 billion each year

A new Pain Medicine Position Paper published by leaders of the American Academy of Pain Medicine (AAPM), reveals businesses lose $61 billion annually due to ineffective pain care and the lack of optimal pain care delivery. Leaders from the organization are now implementing and teaching a new, "population-based" approach to delivering care with the goal of alleviating pain so patients can get on with their lives.

AAPMedicine's President Rollin M. Gallagher, MD MPH comments, "Pain affects everyone, and for many millions, pain becomes chronic, a scourge that affects every part of their lives--their work, their hobbies, their friendships, their families, their sex, their fun, their finances, their mood, and even their fundamental sense of identity, who they are. According to the National Institutes of Health, pain is one of our most important national health problems, costing the American public more than $100 billion each year in health care, compensation and litigation. The AAPMedicine's Position Paper offers solutions that will fundamentally change the way pain is approached in the health care system. The Paper proposes a population-based approach to pain management that will both improve the competency of the health care system to manage pain for the millions of patients suffering needlessly in hospitals with acute pain and on into their lives with chronic pain, and will also reduce the cost of pain to our society. People will be able to work who couldn't work before. People who work will work longer, better and more productively. People with terminal cancer will die in comfort, preserving their personal dignity and mitigating the emotional suffering of their families. The Proposal is consistent with the medical home approach being fostered as a solution to the problems besetting our health care system, an approach that emphasizes patient responsibility, early effective treatment, and when pain becomes chronic, competent longitudinal treatment, what we call 'chronic illness management'."

A population-based approach to pain includes stepped care that is designed to deliver timely access to levels of care that are needed to prevent chronic pain from beginning, or when pain persists, minimizing morbidity through effective care:

Step One: Prevention of disease or injury with the use of evidence-based self-care, such as diet, exercise, ergonomics (alteration of work activities) or cessation of smoking and other drug abuse to reduce the risk of injury or disease.

Step Two: If self-care is not working, patient will then visit their primary care physicians for evaluation and management using evidence-based algorithms.

Step Three: If disabling pain persists, the patient will be referred to a pain medicine specialist who will collaborate with a team of providers, including, nurse case managers, psychologists and physical therapists.

Step Four: If the patient remains in disabling pain, he or she will be referred to a pain medicine specialist within a subspecialty of care.

Currently there is no unified organizational model of pain medicine, which has led to ineffective and fragmented pain care with poor outcomes and higher costs than necessary. This fragmentation threatens patient safety and causes the passing of a patient from doctor to doctor for a diagnosis and pain treatment, even though that doctor may have had minimal or even no specific training in chronic pain management. The Academy believes one of the solutions to this complex problem is the establishment of Pain Medicine as a recognized primary medical specialty. This recognition would allow Pain Medicine's specialized knowledge, education, training, and multidisciplinary approach to provide standardized training for all physicians and integrated and comprehensive pain care to millions of Americans suffering with acute, cancer and chronic pain.

One segment of society that has carried the burden of an ineffective pain care delivery system is the business community. It is estimated to cost $61.2 billion annually in lost productive time. The majority of this cost (76.6%) is attributed to reduced performance while at work, not work absence. During the course of two weeks, 13 percent of the total workforce experienced a loss in productive time due to a common pain condition. An estimated 3.8 billion hours of work are also lost annually due to pain. For additional statistics on the cost of pain care to businesses visit www.painmed.org.

As the largest purchasers of healthcare, businesses have much to lose from ineffective pain treatment of their employees. Finding a unified approach to pain medicine is critical. Back pain alone cost businesses $19.8 billion in lost productive time, with almost three-quarters of the cost attributed to complications of back pain from the lack of proper care.

"The ineffective treatment of pain results in an escalating cascade of health care issues. Acute pain that is not treated adequately and promptly results in persistent pain that eventually causes irreversible changes in the brain and spinal cord. This is referred to as neuropathic pain, a neurobiological disorder that is difficult to diagnose and manage. Persistent pain of this nature often results in further bio-psycho-social changes, which in turn result in further pain and increasing disability. This vicious cycle transforms a human being into a patient who unwittingly becomes a burden to himself, his family and society at large. The emotional, societal and financial costs are immeasurable," according to AAPMedicine's Executive Medical Director, Philipp M. Lippe.

Currently there are not enough pain medicine specialists to treat back pain and other pain conditions, and the system for training physicians in the discipline of pain medicine remains insufficient. The Academy's solution calls for better residency training programs in pain medicine, which will lead to better and more cost-effective pain care.

Recognizing pain medicine as a primary medical specialty would also increase federal funding into pain research. As the population ages, there will be an increased need for physicians who have both specific expertise in pain medicine and broader training in the needs of an aging population. An increase in federal funding for pain research is critical to keep pace with the growing problem of pain in America.

Taking these steps will also improve health care coverage for pain care. Insurance companies often refuse to cover pain-relieving treatments, and access to pain rehabilitation is non-existent in many parts of the country. The Veteran's Affairs' medical system has recognized the need for change in pain care and now requires VA health care institutions to provide organized pain assessment and management. Developing an optimal system of pain care delivery would not only address better healthcare for the millions of Americans in daily pain, but its benefits would filter down to both businesses and society. Safe, effective and affordable pain treatment is possible, and the benefits are immeasurable. 


Chonic pain and productivity cost - MedicineNet.com


Sunday, March 07, 2010

NIH grant program: Collaborative Research on the Transition From Acute to Chronic Pain: New Models and Measures in Clinical and Preclinical Pain Research

The overall goal of this FOA is to expand opportunities in pain research that examine the transition from acute to chronic pain. This initiative seeks applications in basic, behavioral, and clinical research that will study the transition from acute to chronic pain states in temporomandibular disorders and other orofacial, craniofacial, and relevant, comorbid painful disorders. Collaborative, multidisciplinary applications from research teams with expertise in chronic pain conditions and relevant expertise outside the pain field are encouraged; use of the multi-principal investigator/project director model is especially relevant to this initiative. Studies that involve considerable risk but with the potential for breakthroughs in the field are strongly encouraged.

Pain conditions are a major health problem in the US and their economic burden approaches $100 billion per year in lost productivity and medical expenses. These conditions lead to medical morbidity and a reduced quality of life for millions of Americans. The NIDCR is committed to supporting research in temporomandibular joint and muscle disorders (TMJMDs) and other chronic orofacial pain conditions. It is estimated that TMJMDs affect approximately 10 million individuals, the majority of them women during their childbearing age. It is currently unclear how many individuals experiencing acute pain in the temporomandibular joint and muscles will develop a chronic, persistent pain condition. For the most part, acute temporomandibular joint and muscle pain resolves with no or minimal treatment. But for those who develop chronic TMJMD, the effects can be debilitating. Some pain symptoms can be alleviated by analgesics but there are no effective treatments to completely resolve chronic TMJMD or other chronic pain conditions. Some drugs that are used have unwanted side effects that limit their prolonged use or have a low response rate or reduced efficacy. Most current pharmaceutical and behavioral therapies for chronic pain conditions focus on the symptoms, but do not target the underlying mechanisms. Also, these therapies were developed and tested based on our understanding of acute pain mechanisms. None are targeted to prevent the transition to a chronic pain state.

We currently have a relatively incomplete understanding of the etiology and pathology of chronic TMJMDs and other chronic pain conditions. A largely unaddressed challenge is our lack of knowledge in identifying who will transition to a chronic pain state and how to treat patients to prevent this transition. We need to understand, mechanistically, how pain changes from an acute, high threshold response to a chronic, spontaneous, low threshold, dysfunctional painful condition. We do not fully understand how acute pain progresses to chronic pain at any level, from the molecular to behavioral.

Current preclinical and clinical models of pain do not replicate all aspects of human chronic pain states. Current measures of pain in both animals and humans usually rely on evoked responses and do not reflect the spontaneous and recurrent pain in chronic conditions. Most basic, preclinical research has focused on mechanisms, molecules, and circuitry involved in acute pain. This knowledge has then been applied to and validated in human studies. While this translational approach is important, little reverse translation has occurred in the pain field, where mechanistic and observational studies in humans are designed to inform animal research in order to validate and examine in more detail the mechanisms underlying pain. Knowledge gained through a combination of human and animal model studies will improve the development of therapeutic approaches for chronic pain conditions.

The unmet need in the pain field is the effective prevention and treatment of chronic pain conditions. In order to begin to meet this need, an emphasis on research at the transition from acute to chronic pain is needed to understand how neurophysiological changes during this period of time lead to chronic pain. In addition, new clinical and preclinical models of pain conditions and new measures of pain designed to better reflect chronic human pain are needed. These measures call for objective, non-invasive, functional approaches and might include brain imaging and behavioral assessments. By changing the research focus and providing new tools to study pain, we will be able to predict who is at risk of developing chronic pain conditions and to develop novel therapies to prevent the transition to chronicity.

NIDCR and NIH supported basic and clinical pain research is, in large part, addressing the mechanisms of acute nociceptive responses after inflammatory insult or nerve damage has developed into a chronic pain condition, but has not been centered on how the transition to chronicity occurs. In many respects, biological and behavioral changes established at the transition leading to persistent pain represent a disease state of the nervous system and provide our best opportunities to prevent the induction of chronic pain. The overriding concern is that current research is not focused on understanding how chronic pain conditions emerge from an acute painful event or a pain-free state.

This FOA addresses the mission of the NIDCR to improve oral, dental and craniofacial health by performing and supporting basic and clinical research. This Initiative aligns with the NIDCR Strategic Plan 2009-2013 NIDCR Strategic Plan 2009-2013, Goal I, Bring the best science to bear on problems in oral, dental and craniofacial health and Goal III, Identify innovative clinical research avenues to improve oral, dental and craniofacial health. This Initiative also aligns with the NIH Director's research themes of utilizing comprehensive, high throughput technologies to enhance progress in human disease and translating basic science into new and better treatments in order to more rapidly improve diagnostic and therapeutic approaches in medical practice.

The objectives of this FOA are to: 1) assemble research teams with expertise in pain research and related expertise outside the pain field that will provide collaborative, multidisciplinary approaches to answer crucial questions about the transition from acute to chronic pain; 2) discover biological and behavioral mechanisms that drive the transition from an acute, protective pain state to a chronic dysfunctional pain condition; 3) develop new clinical and preclinical models and measures of pain that will be essential to identify and characterize these mechanisms.

To be responsive to this FOA, applications must specifically address mechanisms of transition from acute to chronic pain. These studies can range from underlying molecular mechanisms, cellular and circuit-level analyses, clinical studies, animal and human behavioral research, to epidemiological approaches. Responsiveness will be evaluated by NIDCR Staff and non-responsive applications will not be reviewed.

The types of research being sought cover the spectrum of biomedicine from basic biological approaches to human behavioral studies to patient-oriented and population research. Comprehensive approaches utilizing new technologies are encouraged. Reverse translational approaches where initial human studies are designed to inform and drive basic mechanistic studies or are designed specifically to develop preclinical validation of mechanisms or therapeutic targets are also being sought.


Thursday, March 04, 2010

BBC News - Hand-held device on trial for migraine sufferers

A new hand-held device that delivers a magnetic pulse to the back of the head could become an alternative to drug treatment for people with migraines.

A trial found that 40% of patients were pain free two hours after using the device.

Research showed there were no serious side-effects and patients found the device easy to use at home.

However, doctors say more research is needed to work out the timing of the doses.

Experts from the Albert Einstein College of Medicine in New York carried out the trial to assess the safety and effectiveness of the device.

Previous trials have only involved large, expensive devices which have to be used in a clinic.

Electrical events

The hand-held device emits a single-pulse transcranial magnetic stimulation (sTMS), thought to disrupt the electrical events in the brain which cause the preliminary symptoms of migraines with aura.

Auras are sensory or visual disturbances that occur before a migraine headache sets in.

These include visual symptoms such as spots of light and zigzag lines. Other symptoms include tingling, numbness and difficulties with speaking.

Two hundred patients were asked to use the device to treat migraines with aura over three months. Half of those patients were given placebo treatment.

The findings, to be published in The Lancet Neurology, showed that the real magnetic pulse from the device was significantly more effective than placebo treatment. More patients were pain free two, 24 and 48 hours afterwards.

Dr Hans-Christoph Diener, from University Hospital Essen in Germany, said: "The use of sTMS could be a major step forward in the treatment of migraine with aura, particularly in patients in whom presently available drug treatment is ineffective."

Wendy Thomas, chief executive of the Migraine Trust, welcomed the new trials but stressed that more research into migraines would be needed before patients could access the treatment.

"We look forward to hearing the results of further sTMS trials in the future.

"Migraine and headache are the least publicly funded of all neurological conditions in the UK, particularly relative to their economic impact," she said.

  •  They affect about 18% of women and 6% of men in the USA and Western Europe
  •  There are two major forms of migraine - with aura and without aura.
  •  Migraine with aura affects about 20-30% of patients
  •  Migraine with aura is characterised by symptoms which usually precede the onset of a headache
  • http://news.bbc.co.uk/2/hi/health/8547042.stm

    The brain scanner that feels your pain - New Scientist

    Pain intensity, the most personal of experiences, can now be measured from the outside, say researchers who scanned the brains of young men who were fresh out of the operating theatre.

    Their claim reopens the debate over whether pain can be measured objectively. It might even be possible to gauge the pain felt by newborn babies, fetuses, "locked-in" patients, who can't communicate with the outside world, and animals.

    "The definition of pain is that it is subjective, and until now an objective measurement has remained elusive," says Morten Kringelbach of the University of Oxford, who has previously worked on a method of objective pain measurement and was not involved in the most recent work.

    Functional MRI scans have been used before to identify brain areas that "light up" when someone is in pain. Because oxygenated and deoxygenated blood have different levels of magnetisation they look different under MRI. A technique for analysing fMRI scans called BOLD, for blood-oxygen-level dependent, exploits this difference to determine which areas are most active: high oxygen is a sign that a brain region is particularly active. While BOLD can reveal if the amount of oxygen flowing to a particular region has increased or decreased, it doesn't measure by how much.

    Now Tara Renton of King's College London has used an alternative way of analysing fMRI scans called arterial spin labelling (ASL) to measure how much oxygenated blood is flowing through particular areas. ASL is not new but has only recently been applied to the study of pain.

    In regions of the brain associated with feeling pain, Renton and her team found that the amount of oxygenated blood correlated with the intensity of pain described by 16 young men, just after they had had their wisdom teeth removed.

    Renton, who described the findings at King's College London on 24 February but has not yet published them, says her team's ASL technique is the first objective measure of ongoing pain intensity. In earlier experiments, volunteers were pricked with a pin or touched with a hotplate. But a short sharp shock provides a simplistic view of pain that doesn't take into account the emotional response to longer-lasting pain, which can affect its perceived intensity, says Renton.

    The group are developing their ASL-based technique as a potential alternative to existing methods of assessing the effectiveness of novel analgesics during clinical trials. At the moment, researchers have to rely on a subjective description: volunteers and patients are often asked to describe the level of their pain by placing it on a "visual analogue scale", from 1 to 10. But as Renton says, "a line on a page is really a rather inadequate measure of pain".

    David Borsook, who leads the Pain and Analgesia Imaging and Neuroscience group at McLean Hospital in Boston, agrees. "Whilst it offers a reasonable guesstimate of the amount of pain a person is in, it's not objective, and there is great variation in responses."

    Brain scans could help identify which areas are involved in an individual's pain, perhaps leading to personalised treatments that target those areas. An individual's brain activity might guide a choice between different drugs or counselling, say. "Right now there is little objective data for a clinician to use to choose one drug over another," says Robert Coghill, a neurobiologist at Wake Forest University School of Medicine in North Carolina. "Different patterns of activation might predict the success of different therapies."

    Of course, some big challenges remain. "The response to pain may vary throughout the day, depending on what you're thinking about, and we don't know why," says Kringelbach. There are also bound to be vast differences in the level of brain activation that indicates a given degree of pain in one person compared with another. "The differences haven't been systematically examined yet," says Coghill.

    Even if we can overcome these difficulties, can pain really be reduced to a mere blip on a brain scan? It is after all an experience that blends emotional and physical responses in a highly complex way. "The hunt for an objective measure of pain is a fool's errand," says Stuart Derbyshire, who researches pain at the University of Birmingham, UK. He adds that, since pain is a subjective experience, objective measurements don't really tell us that much anyway. "We will always need to rely on subjective measures," he says.

    Richard Gracely at the University of Michigan, Ann Arbor, agrees. "It's like saying you can measure love, or the beauty of a painting, objectively. Pain is such a private, personal experience. You can only validate what you've measured by asking patients how much pain they're in, so why not just ask them in the first place?"

    In some cases, though, it is not possible to ask. Jeffrey Mogil, who researches pain at McGill University in Montreal, Canada, says a technique like Renton's could be used to measure the level of pain in patients with locked-in syndrome or who are in a vegetative state.

    Another question is whether it might be used to help resolve the contentious question of whether fetuses feel pain. There are some obvious hurdles to scanning a fetus's brain. You can't stabilise its head inside the scanner, and blood flow is very low because it is so small. Borsook also worries about the high magnetic field produced by fMRI: "Nobody knows if it would be dangerous, but it might affect the developing brain in some way."

    Despite these challenges most think some form of brain scanning is our best bet for measuring fetal pain. "I think in the not-too-distant future it will be feasible to image the fetus using ASL," says Coghill.

    The new technique might also allow us to explore animal pain - both so that it can be compared with the human variety, and because it might be possible to test drugs for pain relief on animals. Mogil says that while there are behavioural indicators for pain in animals - for example, mice lick their paws when in pain - assessing ongoing pain is much harder.

    Mogil also raises the intriguing idea of using objective pain measurement on someone who might want to hide the true extent of their suffering. "An opiate addict might exaggerate how much pain they're in, in order to be prescribed opiate painkillers, for example," he says.

    But Coghill warns against disregarding someone's description of pain in favour of an objective measure. "In the US, insurance companies would jump on an objective method of measuring pain, but this could mean that certain people with different patterns of activation lose out," he says. "We need to ensure that patients are never in a position where they are denied treatment."
    He says that objective measurements of pain might be improved by finding indicators for how someone was dealing with it. But he emphasises that patient pain ratings should always have a role in pain assessment. "It's not impossible to have an objective measurement of pain, but this will ultimately need to be complemented by subjective reports."


    Pain - A symptom or a disease?

    There is still disagreement over whether it's possible to measure pain objectively. But attempts to do so are already driving calls for pain to be recognised as a disease in its own right, rather than a mere symptom.

    On 1 March a group of UK pain researchers gathered in London to complain about the way pain is viewed and treated. They argued that far too many people in the world get no treatment for their pain, partly because we are just starting to understand the underlying causes, and partly because of cultural attitudes to pain.

    Beverly Collett, consultant in pain medicine at the University Hospitals of Leicester, described the scale of the problem in the UK, where she says 7.8 million people are living with chronic pain. "Of these, 25 per cent will lose their jobs and 22 per cent will develop depression." The cost of pain is estimated at over €200 billion per year in Europe and $150 billion per year in the US.

    Irene Tracey of the Pain Imaging Neuroscience Group at the University of Oxford says this suffering is unacceptable. She highlights cultural attitudes which encourage people to put up with pain, rather than seeking treatment - including sayings like "no pain, no gain".

    She and Collett are calling for pain to be treated as a disease, rather than a symptom as is the case at the moment. This would hopefully emphasise its seriousness and lead to more extensive treatment.

    Tracey and her colleague Catherine Bushnell recently reviewed the last 10 years of imaging research and concluded that chronic pain is associated with functional, structural and chemical changes in the brain, thus putting it into the realm of a disease state (The Journal of Pain, DOI: 10.1016/j.jpain.2009.09.001). "Chronic pain fits the definition of a disease," says Tracey.

    She hopes that imaging techniques (see main story) will also be used to diagnose pain within the next 5 to 10 years. "It's very hard to unravel the complexities of pain from a verbal response," says Tracey. "The use of imaging to measure pain objectively is potentially very powerful."


    Wednesday, March 03, 2010

    New biomedical search engine – Novoseek

    What is novoseek

    Search engine for biomedical literaturein MedlineFull Text publications and US Grants that will help you to:

    • Retrieve meaningful documents related to your search.
    • Narrow your search to find results in the relevant scientific journals.
    • Identify the most relevant biomedical concepts to your query.