Thursday, March 04, 2010

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."

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