Mansour AR

Pain. 2013 Oct;154(10):2160-8. doi: 10.1016/j.pain.2013.06.044.

Abstract
Neural mechanisms mediating the transition from acute to chronic pain remain largely unknown. In a longitudinal brain imaging study, we followed up patients with a single sub-acute back pain (SBP) episode for more than 1year as their pain recovered (SBPr), or persisted (SBPp) representing a transition to chronic pain. We discovered brain white matter structural abnormalities (n=24 SBP patients; SBPp=12 and SBPr=12), as measured by diffusion tensor imaging (DTI), at entry into the study in SBPp in comparison to SBPr. These white matter fractional anisotropy (FA) differences accurately predicted pain persistence over the next year, which was validated in a second cohort (n=22 SBP patients; SBPp=11 and SBPr=11), and showed no further alterations over a 1-year period. Tractography analysis indicated that abnormal regional FA was linked to differential structural connectivity to medial vs lateral prefrontal cortex. Local FA was correlated with functional connectivity between medial prefrontal cortex and nucleus accumbens in SBPr. As we have earlier shown that the latter functional connectivity accurately predicts transition to chronic pain, we can conclude that brain structural differences, most likely existing before the back pain-inciting event and independent of the back pain, predispose subjects to pain chronification.

Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

PubMed Abstract:  http://www.ncbi.nlm.nih.gov/pubmed/24040975

From the Wall Street Journal

IN THE LAB

October 7, 2013, 7:07 p.m. ET

Why Does Chronic Pain Hurt Some People More? Brain Research Reveals New Clues

http://online.wsj.com/article/SB10001424052702304171804579121292600631048.html

Why does pain from the same type of injury linger in some people but not others?

Genetics and brain-based biological factors are the latest frontier of research on chronic pain, along with personality traits, coping strategies and life experiences. The question is a riddle researchers have been trying to solve for decades.

Better identifying which injuries may lead to chronic pain, defined as lasting beyond normal healing for at least three months, is hugely important for the 100 million Americans who suffer from it. Lower-back pain is the most common type, with nearly one-third of U.S. adults reporting in 2010 having experienced it within the previous three months, according an Institute of Medicine report on pain.

Often the initial cause of the pain is never identified. But for pain experts the bigger mystery is why pain lingers in some patients, and what combination of biological, psychological and social factors contribute to it.

A new study published in September by scientists at Northwestern Medical School aims to figure out how the brains of those who suffer from chronic pain differ from those who only experience temporary pain after a back injury. Such findings may be helpful in distinguishing those who need additional treatment from those whose pain would subside on its own. The work may also help find a way to prevent the pain from lingering.

“The more we look in the brain, the more predictors we find in it,” says A. Vania Apkarian, one of the study authors and a Northwestern physiology professor.

Dr. Apkarian’s team has been imaging the brains of patients who had a recent back injury for the last five years, looking for differences in the structure and functioning of the brain in patients who develop chronic pain. This type of longitudinal study is rare in pain research and difficult to carry out. The group has collected 3,000 brain scans so far.

In the new study published two weeks ago in the journal Pain, the researchers looked in the white matter of the brain, which consists of axons that transmit messages to and from different parts. This road map is the circuitry through which the body and brain communicate about pain, Dr. Apkarian says.

The scientists found distinct abnormalities in the road map of participants who ended up developing chronic pain over a one-year period. It forecast with 80% to 100% accuracy which individuals developed that pain, a surprisingly strong predictor.

Since the first brain scans in these participants were taken after the back injury occurred, the researchers don’t know if the changes in brain biology preceded the pain. They suspect that they did, because in looking at non-injured, healthy subjects, they found that a proportion already have this abnormal pathway, which didn’t change over the first year of study.

It isn’t clear exactly why the abnormalities may allow or cause chronic pain, but the axons in the white matter are coated with a sheath known as myelin, and the myelin and axons appear distorted compared with typical axons.

Independent experts say the work is encouraging but urge caution about its clinical use in predicting risk of chronic pain for any single individual. The findings need to be replicated in another group of patients first, says M. Catherine Bushnell, a pain researcher and scientific director of the National Center for Complementary and Alternative Medicine, who called the study “heroic” because of the difficulty in conducting this type of research. It also isn’t clear whether the same changes would be expected for patients suffering from a different type of pain, she says.

Dr. Apkarian’s group also looked, in a previous study published last year, at anatomical changes in the brain’s gray matter, which helps control sensory perception, muscles and emotion. That investigation found that chronic pain appeared to reorganize brain structure. They found unusually high levels of communication between two regions, the prefrontal cortex and nucleus accumbens.

“The more they talk to each other, the more likely someone is going to become a chronic pain patient,” Dr. Apkarian says.

He and his colleagues are beginning a study this month in which they are trying to develop a treatment using a combination of medications already on the market to prevent acute pain from morphing into chronic pain.

Beyond the brain, genetics, personality, emotional state and coping style have been tied to severity of pain and chronic pain. Some evidence suggests that those who seek less risk and are more fearful of pain are more likely to experience pain more strongly. That may be due to increased activation of the amygdala, according to Rupert Conrad, head of research in the department of psychosomatic medicine and psychotherapy at Bonn University in Germany.

For instance, staff scientist Hyungsuk Kim and his colleagues at the National Institute of Nursing Research conducted a study in which healthy people were asked to put their hand in ice-cold water for as long as possible. Some withdrew their hand immediately while others kept their hands in for more than three minutes. When they looked at personality characteristics, they found that those who were more persistent or liked to try new experiences were more likely to keep their hands in for longer.

Another goal in the field of identifying objective markers of pain is to help distinguish those patients who actually feel pain from the minority who report discomfort in order to get painkillers.

Research on a “pain personality” hasn’t led to a consensus from researchers so far. And even when variables like depression are linked to chronic-pain sufferers on the whole, it is still incredibly difficult to predict whether any individual is a likely chronic-pain candidate.

Elliot Krane, director of the Pediatric Pain Management Program at Lucile Packard Children’s Hospital at Stanford University, says there are “unquestionably” intrinsic differences in people’s sensitivity to pain. But psychological factors make a difference as well, he says. High-anxiety individuals can exacerbate their pain.

One of his patients, a girl with complex regional pain syndrome, an often chronic condition in which pain tends to start from an extremity and radiates throughout the body, had been treated and was doing well enough to run a 10-kilometer race recently. But she twisted her ankle during the event. The child’s mother emailed that she was panicking that her daughter was going to get CRPS again, Dr. Krane says.

His advice to her? “Number one, don’t panic. If you panic, she’ll panic,” he says. “We don’t want her pain enhanced by the anxiety.”

Write to Shirley S. Wang at shirley.wang@wsj.com