First objective measure of pain discovered in brain scan patterns

For the first time, scientists have been able to predict how much pain people are feeling by looking at images of their brains, according to a new study led by the University of Colorado Boulder.

The findings, published today in the New England Journal of Medicine, may lead to the development of reliable methods doctors can use to objectively quantify a patient’s pain. Currently, pain intensity can only be measured based on a patient’s own description, which often includes rating the pain on a scale of one to 10. Objective measures of pain could confirm these pain reports and provide new clues into how the brain generates different types of pain.

The new research results also may set the stage for the development of methods using brain scans to objectively measure anxiety, depression, anger or other emotional states.

“Right now, there’s no clinically acceptable way to measure pain and other emotions other than to ask a person how they feel,” said Tor Wager, associate professor of psychology and neuroscience at CU-Boulder and lead author of the paper.

The research team, which included scientists from New York University, Johns Hopkins University and the University of Michigan, used computer data-mining techniques to comb through images of 114 brains that were taken when the subjects were exposed to multiple levels of heat, ranging from benignly warm to painfully hot. With the help of the computer, the scientists identified a distinct neurologic signature for the pain.

“We found a pattern across multiple systems in the brain that is diagnostic of how much pain people feel in response to painful heat.” Wager said.

Going into the study, the researchers expected that if a pain signature could be found it would likely be unique to each individual. If that were the case, a person’s pain level could only be predicted based on past images of his or her own brain. But instead, they found that the signature was transferable across different people, allowing the scientists to predict how much pain a person was being caused by the applied heat, with between 90 and 100 percent accuracy, even with no prior brain scans of that individual to use as a reference point.

The scientists also were surprised to find that the signature was specific to physical pain. Past studies have shown that social pain can look very similar to physical pain in terms of the brain activity it produces. For example, one study showed that the brain activity of people who have just been through a relationship breakup — and who were shown an image of the person who rejected them — is similar to the brain activity of someone feeling physical pain.

But when Wager’s team tested to see if the newly defined neurologic signature for heat pain would also pop up in the data collected earlier from the heartbroken participants, they found that the signature was absent.

Finally, the scientists tested to see if the neurologic signature could detect when an analgesic was used to dull the pain. The results showed that the signature registered a decrease in pain in subjects given a painkiller.

The results of the study do not yet allow physicians to quantify physical pain, but they lay the foundation for future work that could produce the first objective tests of pain by doctors and hospitals. To that end, Wager and his colleagues are already testing how the neurologic signature holds up when applied to different types of pain.

“I think there are many ways to extend this study, and we’re looking to test the patterns that we’ve developed for predicting pain across different conditions,” Wager said. “Is the predictive signature different if you experience pressure pain or mechanical pain, or pain on different parts of the body?

“We’re also looking towards using these same techniques to develop measures for chronic pain. The pattern we have found is not a measure of chronic pain, but we think it may be an ‘ingredient’ of chronic pain under some circumstances. Understanding the different contributions of different systems to chronic pain and other forms of suffering is an important step towards understanding and alleviating human suffering.”

Amputee pain linked to brain retaining picture of missing limb

Changes in the brain following amputation have been linked to pain arising from the missing limb, called ‘phantom pain’, in an Oxford University brain imaging study.

Arm amputees experiencing the most phantom limb pain were found to maintain stronger representation of the missing hand in the brain – to the point where it was indistinguishable from people with both hands.

The researchers hope their identification of brain responses correlated with the level of phantom pain can aid the development of treatment approaches, as well as increase understanding of how the brain reorganises and adapts to new situations.

The Oxford University researchers, along with Dr David Henderson-Slater of the Nuffield Orthopaedic Centre, report their findings in the journal Nature Communications.

‘Almost all people who have lost a limb have some sensation that it is still there, and it’s thought that around 80% of amputees experience some level of pain associated with the missing limb. For some the pain is so great it is hugely debilitating,’ says first author Dr Tamar Makin of the Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) at Oxford University.

Treatments for phantom limb pain tend to be limited to standard drugs for pain relief. The origin of the pain is not well understood. There may be many factors that lead to the pain, including injured nerve endings where the limb was lost and changes in the brain areas connected with the missing limb.

Lynn Ledger, a 48 year old trained therapist and advisor to charities on management training from Nottingham, took part in the study. She had her left arm amputated halfway between the elbow and shoulder in May 2009 after radiotherapy for a rare form of cancer failed to deal with an extensive tumour in her arm. She experiences severe pain as if it was coming from the missing limb.

‘I’ve pretty much tried everything to deal with the pain but nothing has worked,’ Lynn says. ‘There are no drug treatments that work because the condition is not fully understood yet. I can only use various distraction techniques, breathing exercises and mental imagery techniques, to help me manage the pain.

‘It’s very hard to describe the pain to others. I have a nonexistent limb, but I still sense it and feel pain. It’s like: imagine you are wearing a lady’s evening glove that stretches from the fingers up the arm past the elbow. But everywhere the glove covers, it’s as if it’s constantly crushing your arm. There are also shooting pains and intensely painful burning sensations that come and go, but the crushing pain is constant.

‘When I heard about this study I wanted to be involved as it was trying to improve people’s understanding of the condition.’

Kirsty Mason from Bracknell is 22 and about to start a new job as a support worker for people with mental health problems, as well as being an assessor for disabled students for their assisted technology needs. She lost her right arm four years ago just below the elbow after blacking out at a train station and falling on to the rails just ahead of a train coming in. She woke to find a wheel stopped on her arm. Since then she’s learned to write with her left hand and began driving last year. She also took part in the brain imaging study.

‘With me it’s all or nothing,’ Kirsty says of her phantom pain. ‘I get the usual pins and needles and a constant niggling pain that I can shut out by doing other things. But the worst pain is a kind of burning. It’s less frequent but it’s intense: 90-100 on the scale. It sounds silly, but the only thing I can do is stick my hand in a freezer. It numbs it.

She says: ‘I can feel my fist clenching, my fingernails digging in. I can see the hand isn’t there but the sensation is so realistic. If someone throws me a ball, I’ll move both hands to catch it. I’ll put out both hands if I fall over.’

The Oxford University team used MRI imaging to study how the phantom limb pain felt by people who have had an arm amputated is related to changes in the brain.

They compared MRI data for 18 amputees, with differing levels of phantom pain, with 11 individuals born with one hand through a limb deficiency and a control group of 22 adults with two full limbs.

The amputations had been done 18 years ago on average, but the participants still experienced sensations for the missing arm. By asking them to move the fingers of the phantom limb while in the MRI scanner, the researchers were able to look at how the missing hand is represented in the brain.

They found that the brain maintained its representation of the hand, even though the limb was no longer there. The extent to which the representation was maintained was linked to the strength and frequency of the pain the amputees felt: those feeling the greatest pain retained the strongest representation of the missing hand.

‘We were astonished to find that in amputees experiencing strong phantom pain, the brain’s response was indistinguishable from that seen in people with intact limbs,’ says Dr Makin.

The researchers found that the amount of grey matter in the phantom hand area of the brain was reduced in amputees compared to those with two hands. But again this was linked to the amount of pain amputees felt. Those experiencing stronger pain showed less structural degeneration in the missing hand area following the loss of the limb.

However, while those with strong phantom limb pain maintained the local brain structure and function for the missing hand, there was evidence that connections to other parts of the brain were disrupted more.

In particular, the representation of the missing hand was more out of synch with the area looking after the other hand on the opposite side of the brain.

Dr Makin says: ‘Most people experience “phantom” sensations in a missing limb after amputation. This disconnect between the physical world and what they are experiencing appears to be linked to a functional detachment in the brain. There seem to be reduced connections between the missing limb part of the brain and the rest of the cortex that’s involved in movement.

‘Our results may encourage rehabilitation approaches that aim to re-couple the representation of the phantom hand with the external sensory environment.’

Preventing chronic pain with stress management

For chronic pain sufferers, such as people who develop back pain after a car accident, avoiding the harmful effects of stress may be key to managing their condition. This is particularly important for people with a smaller-than-average hippocampus, as these individuals seem to be particularly vulnerable to stress. These are the findings of a study by Dr. Pierre Rainville, PhD in Neuropsychology, Researcher at the Research Centre of the Institut universitaire de gériatrie de Montréal (IUGM) and Professor in the Faculty of Dentistry at Université de Montréal, along with Étienne Vachon-Presseau, a PhD student in Neuropsychology. The study appeared in Brain, a journal published by Oxford University Press.

“Cortisol, a hormone produced by the adrenal glands, is sometimes called the ‘stress hormone’ as it is activated in reaction to stress. Our study shows that a small hippocampal volume is associated with higher cortisol levels, which lead to increased vulnerability to pain and could increase the risk of developing pain chronicity,” explained Étienne Vachon-Presseau.

As Dr. Pierre Rainville described, “Our research sheds more light on the neurobiological mechanisms of this important relationship between stress and pain. Whether the result of an accident, illness or surgery, pain is often associated with high levels of stress Our findings are useful in that they open up avenues for people who suffer from pain to find treatments that may decrease its impact and perhaps even prevent chronicity. To complement their medical treatment, pain sufferers can also work on their stress management and fear of pain by getting help from a psychologist and trying relaxation or meditation techniques.” 

Research summary

This study included 16 patients with chronic back pain and a control group of 18 healthy subjects. The goal was to analyze the relationships between four factors: 1) cortisol levels, which were determined with saliva samples; 2) the assessment of clinical pain reported by patients prior to their brain scan (self-perception of pain); 3) hippocampal volumes measured with anatomical magnetic resonance imaging (MRI); and 4) brain activations assessed with functional MRI (fMRI) following thermal pain stimulations. The results showed that patients with chronic pain generally have higher cortisol levels than healthy individuals. 

Data analysis revealed that patients with a smaller hippocampus have higher cortisol levels and stronger responses to acute pain in a brain region involved in anticipatory anxiety in relation to pain. The response of the brain to the painful procedure during the scan partly reflected the intensity of the patient’s current clinical pain condition. These findings support the chronic pain vulnerability model in which people with a smaller hippocampus develop a stronger stress response, which in turn increases their pain and perhaps their risk of suffering from chronic pain. This study also supports stress management interventions as a treatment option for chronic pain sufferers.

(Image: iStock)

People in a vegetative state may feel pain

It is a nightmare situation. A person diagnosed as being in a vegetative state has an operation without anaesthetic because they cannot feel pain. Except, maybe they can.

Alexandra Markl at the Schön clinic in Bad Aibling, Germany, and colleagues studied people with unresponsive wakefulness syndrome (UWS) – also known as vegetative state – and identified activity in brain areas involved in the emotional aspects of pain. People with UWS can make reflex movements but can’t show subjective awareness.

There are two distinct neural networks that work together to create the sensation of pain. The more basic of the two – the sensory-discriminative network – identifies the presence of an unpleasant stimulus. It is the affective network that attaches emotions and subjective feelings to the experience. Crucially, without the activity of the emotional network, your brain detects pain but won’t interpret it as unpleasant.

Using PET scans, previous studies have detected activation in the sensory-discriminative network in people with UWS but their findings were consistent with a lack of subjective awareness, the hallmark of the condition.

Now Markl and her colleagues have found evidence of activation in the affective or emotional network too (Brain and Behavior).

Her team gave moderately painful electric shocks to 30 people with UWS, while scanning their brains using fMRI. Sixteen people had some kind of brain activation – seven only in the sensory network but nine in the affective network as well.

These results question whether some diagnoses should change from UWS to minimally conscious, which is characterised by some level of awareness.

"I don’t think this paper alone will change the clinical approach to people with diagnoses such as UWS," says Donald Weaver at Dalhousie University in Halifax, Nova Scotia, Canada, who was not involved in the work. But it will encourage future study, he says.

Changing a diagnosis depends on whether neurologists are ready to accept alternative ways of diagnosing disorders of consciousness, says Boris Kotchoubey at the Institute of Medical Psychology and Behavioural Neurobiology in Tübingen, Germany, who worked on the study.

Nonetheless, Kotchoubey is confident that the way people with UWS are cared for will change, even if their diagnoses remain the same. “I know that many doctors working with such patients have been instructed to treat their patients as if they can understand them and perceive at least something in the environment, perhaps pain, pleasure, or emotion,” he says.

But not all people are treated this way. Prior to the study, one of the people in Markl’s study was given no anaesthesia before a tracheotomy, which involves an incision in the neck to allow breathing without using the nose or mouth. As people with UWS are clinically considered unable to understand pain, doctors do not have to give an anaesthetic.

The pain puzzle: Uncovering how morphine increases pain in some people

For individuals with agonizing pain, it is a cruel blow when the gold-standard medication actually causes more pain. Adults and children whose pain gets worse when treated with morphine may be closer to a solution, based on research published in the January 6 on-line edition of Nature Neuroscience.

"Our research identifies a molecular pathway by which morphine can increase pain, and suggests potential new ways to make morphine effective for more patients," says senior author Dr. Yves De Koninck, Professor at Université Laval in Quebec City. The team included researchers from The Hospital for Sick Children (SickKids) in Toronto, the Institut universitaire en santé mentale de Québec, the US and Italy.

New pathway in pain management

The research not only identifies a target pathway to suppress morphine-induced pain but teases apart the pain hypersensitivity caused by morphine from tolerance to morphine, two phenomena previously considered to be caused by the same mechanisms.

"When morphine doesn’t reduce pain adequately the tendency is to increase the dosage. If a higher dosage produces pain relief, this is the classic picture of morphine tolerance, which is very well known. But sometimes increasing the morphine can, paradoxically, makes the pain worse," explains co-author Dr. Michael Salter. Dr. Salter is Senior Scientist and Head of Neurosciences & Mental Health at SickKids, Professor of Physiology at University of Toronto, and Canada Research Chair in Neuroplasticity and Pain.

"Pain experts have thought tolerance and hypersensitivity (or hyperalgesia) are simply different reflections of the same response," says Dr. De Koninck, "but we discovered that cellular and signalling processes for morphine tolerance are very different from those of morphine-induced pain."

Dr. Salter adds, “We identified specialized cells – known as microglia – in the spinal cord as the culprit behind morphine-induced pain hypersensitivity. When morphine acts on certain receptors in microglia, it triggers the cascade of events that ultimately increase, rather than decrease, activity of the pain-transmitting nerve cells.”

The researchers also identified the molecule responsible for this side effect of morphine. “It’s a protein called KCC2, which regulates the transport of chloride ions and the proper control of sensory signals to the brain,” explains Dr. De Koninck. “Morphine inhibits the activity of this protein, causing abnormal pain perception. By restoring normal KCC2 activity we could potentially prevent pain hypersensitivity.” Dr. De Koninck and researchers at Université Laval are testing new molecules capable of preserving KCC2 functions and thus preventing hyperalgesia.

The KCC2 pathway appears to apply to short-term as well as to long-term morphine administration, says Dr. De Koninck. “Thus, we have the foundation for new strategies to improve the treatment of post-operative as well as chronic pain.”

Dr. Salter adds, “Our discovery could have a major impact on individuals with various types of intractable pain, such as that associated with cancer or nerve damage, who have stopped morphine or other opiate medications because of pain hypersensitivity.”

Cost of pain

Pain has been labelled the silent health crisis, afflicting tens of millions of people worldwide. Pain has a profound negative effect on the quality of human life. Pain affects nearly all aspects of human existence, with untreated or under-treated pain being the most common cause of disability. The Canadian Pain Society estimates that chronic pain affects at least one in five Canadians and costs Canada $55-60 billion per year, including health care expenses and lost productivity.

"People with incapacitating pain may be left with no alternatives when our most powerful medications intensify their suffering," says Dr. De Koninck, who is also Director of Cellular and Molecular Neuroscience at Institut universitaire en santé mentale de Québec.

Dr. Salter adds, “Pain interferes with many aspects of an individual’s life. Too often, patients with chronic pain feel abandoned and stigmatized. Among the many burdens on individuals and their families, chronic pain is linked to increased risk of suicide. The burden of chronic pain affects children and teens as well as adults.” These risks affect individuals with many types of pain, ranging from migraine and carpel-tunnel syndrome to cancer, AIDS, diabetes, traumatic injuries, Parkinson’s disease and dozens of other conditions.

Electric stimulation of brain releases powerful, opiate-like painkiller

Researchers used electricity on certain regions in the brain of a patient with chronic, severe facial pain to release an opiate-like substance that’s considered one of the body’s most powerful painkillers.

The findings expand on previous work done at the University of Michigan, Harvard University and the City University of New York where researchers delivered electricity through sensors on the skulls of chronic migraine patients, and found a decrease in the intensity and pain of their headache attacks. However, the researchers then couldn’t completely explain how or why.

The current findings help explain what happens in the brain that decreases pain during the brief sessions of electricity, says Alexandre DaSilva, the senior researcher in the study from the University of Michigan School of Dentistry. Other study authors include DaSilva’s PhD student, Marcos DosSantos, and also Dr. Jon-Kar Zubieta from the Molecular and Behavioral Neuroscience Institute.

In their current study, DaSilva and colleagues intravenously administered a radiotracer that reached important brain areas in a patient with trigeminal neuropathic pain (TNP), a type of chronic, severe facial pain. They applied the electrodes and electrically stimulated the skull right above the motor cortex of the patient for 20 minutes during a PET scan (positron emission tomography). The stimulation is called transcranial direct current stimulation (tDCS).

The radiotracer was specifically designed to measure, indirectly, the local brain release of mu-opioid, a natural substance that alters pain perception. In order for opiate to function, it needs to bind to the mu-opioid receptor (the study assessed levels of this receptor).

"This is arguably the main resource in the brain to reduce pain," DaSilva said. "We’re stimulating the release of our (body’s) own resources to provide analgesia. Instead of giving more pharmaceutical opiates, we are directly targeting and activating the same areas in the brain on which they work. (Therefore), we can increase the power of this pain-killing effect and even decrease the use of opiates in general, and consequently avoid their side effects, including addiction."

Most pharmaceutical opiates, especially morphine, target the mu-opioid receptors in the brain, DaSilva says.

The dose of electricity is very small, he says. Consider that electroconvulsive therapy (ECT), which is used to treat depression and other psychiatric conditions, uses amperage in the brain ranging from 200 to 1600 milliamperes (mA). The tDCS protocol used in DaSilva’s study delivered 2 mA, considerably lower than ECT.

Just one session immediately improved the patient’s threshold for cold pain by 36 percent, but not the patient’s clinical, TNP/facial pain. This suggests that repetitive electrical stimulation over several sessions are required to have a lasting effect on clinical pain as shown in their previous migraine study, DaSilva says.

The manuscript appears in the journal Frontiers in Psychiatry. The group just completed another study with more subjects, and the initial results seem to confirm the findings above, but further analysis is necessary.

Next, researchers will investigate long-term effects of electric stimulation on the brain and find specific targets in the brain that may be more effective depending on the pain condition and patients’ status. For example, the frontal areas may be more helpful for chronic pain patients with depression symptoms.

Researchers report progress in quest to create objective method of detecting pain

A method of analyzing brain structure using advanced computer algorithms accurately predicted 76 percent of the time whether a patient had lower back pain in a new study by researchers from the Stanford University School of Medicine.

The study, published online Dec. 17 in Cerebral Cortex, reported that using these algorithms to read brain scans may be an early step toward providing an objective method for diagnosing chronic pain.

“People have been looking for an objective pain detector — a ‘pain scanner’ — for a long time,” said Sean Mackey, MD, PhD, chief of the Division of Pain Medicine and professor of anesthesiology, pain and perioperative medicine, and of neurosciences and neurology. “We’re still a long way from that, but this method may someday augment self-reporting as the primary way of determining whether a patient is in chronic pain.”

The need for a better way to objectively measure pain instead of relying solely on self-reporting has long been acknowledged. But the highly subjective nature of pain has made this an elusive goal. Advances in neuroimaging techniques have initiated a debate over whether this may be possible. Such a tool would be particularly useful in treating very young or very old patients or others who have difficulty communicating, Mackey said.

In a study published last year in PLoS ONE, Mackey and colleagues used computer algorithms to analyze magnetic resonance imaging scans of the brain to accurately measure thermal pain in research subjects 81 percent of the time. But the question remained whether this could be a successful method for measuring chronic pain.

The goal of the new study was to accurately identify patients with lower back pain vs. healthy individuals on the basis of structural changes to the brain, and also to investigate possible pathological differences across the brain.

Researchers conducted MRI scans of 47 subjects who had lower back pain and 47 healthy subjects. Both groups were screened for medication use and mood disorders. The average age was 37.

The idea was to “train” a linear support vector machine — a computer algorithm invented in 1995 — on one set of individuals, and then use that computer model to accurately read the brain scans and classify pain in a completely new set of individuals.

The method successfully predicted the patients with lower back pain 76 percent of the time.

“Lower back pain is the most common chronic condition we deal with,” Mackey said. “In many cases, we don’t understand the cause. What we have learned is that the problem may not be in the back, but in the amplification coming from the back to the brain and nervous system. In this study, we did identify brain regions we think are playing a role in this phenomena.”

Brain imaging insight into cannabis as a pain killer

The pain relief offered by cannabis varies greatly between individuals, a brain imaging study carried out at the University of Oxford suggests.

The researchers found that an oral tablet of THC, the psychoactive ingredient in cannabis, tended to make the experience of pain more bearable, rather than actually reduce the intensity of the pain.

MRI brain imaging showed reduced activity in key areas of the brain that substantiated the pain relief the study participants experienced. 

'We have revealed new information about the neural basis of cannabis-induced pain relief,' says lead researcher Dr Michael Lee of Oxford University's Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB). 

'Cannabis does not seem to act like a conventional pain medicine. Some people respond really well, others not at all, or even poorly,' he says. 'Brain imaging shows little reduction in the brain regions that code for the sensation of pain, which is what we tend to see with drugs like opiates. Instead cannabis appears to mainly affect the emotional reaction to pain in a highly variable way.'

Long-term pain, often without clear cause, is a complex healthcare problem. Different approaches are often needed to help patient manage pain, and can include medications, physiotherapy and other forms of physical therapy, and psychological support. 

For a few patients, cannabis or cannabis-based medications remain effective when other drugs have failed to control pain, while others report very little effect of the drug on their pain but experience side-effects.

'We know little about cannabis and what aspects of pain it affects, or which people might see benefits over the side-effects or potential harms in the long term. We carried out this study to try and get at what is happening when someone experiences pain relief using cannabis,' says Dr Lee.

He adds: ‘Our small-scale study, in a controlled setting, involved 12 healthy men and only one of many compounds that can be derived from cannabis. That’s quite different from doing a study with patients.

'My view is the findings are of interest scientifically but it remains to see how they impact the debate about use of cannabis-based medicines. Understanding cannabis' effects on clinical outcomes, or the quality of life of those suffering chronic pain, would need research in patients over long time periods.'

(The paper ‘Amygdala activity contributes to the dissociative effect of cannabis on pain perception' by Michael C. Lee, Markus Ploner, Katja Wiech, Ulrike Bingel, Vishvarani Wanigasekera, Jonathan Brooks, David K. Menon, Irene Tracey (DOI: 10.1016/j.pain.2012.09.017) will appear in PAIN®, Volume 154, Issue 1 (January 2013) published by Elsevier)

Discovery could eventually help diagnose and treat chronic pain

More than 100 million Americans suffer from chronic pain. But treating and studying chronic pain is complex and presents many challenges. Scientists have long searched for a method to objectively measure pain and a new study from Brigham and Women’s Hospital advances that effort. The study appears in the January 2013 print edition of the journal Pain.

"While we need to be cautious in the interpretation of our results, this has the potential to be an exciting discovery for anyone who suffers from chronic pain," said Marco Loggia, PhD, the lead author of the study and a researcher in the Pain Management Center at BWH and the Department of Radiology at Massachusetts General Hospital. "We showed that specific brain patterns appear to track the severity of pain reported by patients, and can predict who is more likely to experience a worsening of chronic back pain while performing maneuvers designed to induce pain. If further research shows this metric is reliable, this is a step toward developing an objective scale for measuring pain in humans."

Specifically, researchers studied 16 adults with chronic back pain and 16 adults without pain and used a brain imaging technique called arterial spin labeling to examine patterns of brain connectivity (that is, to examine how different brain regions interact, or “talk to each other”). They found that when a patient moved in a way that increased their back pain, a network of brain regions called Default Mode Network exhibited changes in its connections. Regions within the network (such as the medial prefrontal cortex) became less connected with the rest of the network, whereas regions outside network (such as the insula) became connected with this network. Some of these observations have been noted in previous studies of fibromyalgia patients, which suggests these changes in brain connectivity might reflect a general feature of chronic pain, possibly common to different patient populations.

"This is the first study using arterial spin labeling to show common networking properties of the brain are affected by chronic pain," said study author Ajay Wasan, MD, MSc, Director of the Section of Clinical Pain Research at BWH. "This novel research supports the use of arterial spin labeling as a tool to evaluate how the brain encodes and is affected by clinical pain, and the use of resting default mode network connectivity as a potential neuroimaging biomarker for chronic pain perception."