Chronic back pain is associated with marked changes in brain activity compared to acute pain, says a new study from A. Vania Apkarian and colleagues at Northwestern University, Chicago, Illinois, US. In a report published in the September issue of Brain, first author Javeria Hashmi, Apkarian, and colleagues demonstrate a shift over time in brain signatures, or imaged patterns of brain activity, in patients with subacute, short-lasting back pain and those with long-lasting back pain. In general, the representation of pain in the brain shifts over time from classical pain areas to areas implicated in emotion.
This is the first study that examines brain activity in a common pain condition as it transforms over time. The finding of a shift in central nervous system activity in patients moving from acute to chronic pain indicates that there is not just one signature for pain in the brain and could provide new avenues for diagnosis and treatment.
The work is a continuation of an ongoing longitudinal investigation examining changes in brain structure and function in patients with subacute back pain (SBP) as they either recover or develop persistent pain. Previously, Apkarian’s team demonstrated in a yearlong study that differences in functional connectivity between brain areas, and white matter structural differences, can predict the persistence of pain in SBP patients (Baliki et al., 2012, and see PRF related news story on Mansour et al., 2013).
In the current study, the team compared brain signatures between SBP patients, including those who recovered and those whose pain persisted over the course of a year, with chronic back pain (CBP) patients who have experienced back pain for more than a decade. “It’s the first time we’ve done it,” said Apkarian, referring to the study’s longitudinal nature. “It’s been very hard to do.”
First, Apkarian’s team used functional magnetic resonance imaging (fMRI) to compare pain-related brain activity in 94 SBP patients (who had had back pain for less than three months) and 59 CBP patients (who had pain for more than 10 years).
All of the subjects noted and rated instances of spontaneous back pain on an intensity scale of 1 to 100 during their fMRI scans. The images were then analyzed to determine the active regions, distinct from background activity, that were associated with pain perception.
To assign functions to the active regions, the team turned to Neurosynth, a meta-analytic Web-based software that automatically extracts and amasses fMRI data from published research studies (see PRF related news story on Yarkoni et al., 2011). Data from hundreds of brain imaging studies are analyzed to provide a consensus of fMRI data on commonly studied conditions such as “thinking,” “distress,” or “sleep.” “There’s a surprising degree of overlap between individuals,” with regard to brain activity, said Tor Wager, a psychologist and neuroscientist at the University of Colorado, Boulder, US, whose lab developed Neurosynth. Showing conserved areas of brain activity among experimental groups is crucial to any conclusions scientists might draw from their data.
“It gives us a scale of confidence on which we can make our statement,” said Apkarian.
The Apkarian team searched for the terms “pain,” “emotion,” and “reward” following their intuition that subacute pain is more related to classical sensory regions, whereas chronic pain representation might migrate to more affective regions in the brain.
The researchers found that SBP patients demonstrated conserved activity in brain areas including the anterior to mid-insula, thalamus, striatum and lateral parts of the orbitofrontal and inferior cortex, and dorsal anterior cingulate cortex. These areas are known to be involved in acute pain. In contrast, CBP patients exhibited brain activity in areas including the perigenual anterior cingulate cortex, the medial prefrontal cortex, and parts of the amygdala—areas that are considered to mediate emotion.
That finding raised the question of how these distinct brain signatures might arise. To address that question, the researchers analyzed scans of 39 SBP patients followed longitudinally for one year. All of the subjects initially exhibited pain-specific brain activity, including in the insula, anterior cingulate cortex, and thalamus, as expected.
Eventually, 19 of the patients recovered and exhibited no pain-relevant brain activity at one year. But 20 of the patients experienced persisting pain, and that group displayed a transformation in brain activity, with pronounced activity in areas such as the amygdala, medial prefrontal cortex, and basal ganglia, and no sign of previously robust activity in acute pain-related areas. Affirming Apkarian’s ongoing research, SBP patients who had high functional connectivity between the medial prefrontal cortex and nucleus accumbens at the outset of the study were more likely to experience persisting pain.
“[Brain activity] has moved away from sensory representation areas in general to more areas that relate to emotion” in patients with chronic pain, said Apkarian. Brain signatures of pain became more emotional in nature, although, Apkarian stressed, the description by the patients of their pain remained constant.
Brain localization theory, the idea that certain perceptions are only encoded by certain brain regions, has left its mark on psychology and neuroscience. “This is the first unequivocal evidence that that cannot be tenable,” said Apkarian.
“Many people think there’s one system for pain,” said Wager. Now, growing evidence from Apkarian, Wager, and others makes this a difficult proposition.
Besides providing evidence for the idea that pain representation evolves over time, the study provides a possible avenue to explain why treatments that are efficacious for acute pain patients may not work for chronic pain patients with the same injury. “We have to look beyond peripheral sensation to treat pain,” said Apkarian. And he and Wager agreed that brain signatures are a viable future diagnostic tool.
Abdul-Kareem Ahmed is a medical student and freelance science writer in Providence, Rhode Island, US.
Image credit: From Hashmi et al., 2013, courtesy of Oxford University Press