Studying chronic pain in the brain: the complexity and importance

A recent study published in Nature Neuroscience reported that researchers were able to predict chronic pain states from brain activity using machine learning techniques. Their findings provide a new step towards a much-needed improvement in our understanding of what happens in the brain when people experience chronic pain.

Neural signatures of chronic pain
Studying chronic pain comes with numerous challenges. The causes of chronic pain can be very heterogeneous, studies often rely on self-report of pain severity, and sample sizes can be very limited. The research approach taken in the Californian study published last month included implanting participants suffering from chronic pain with electrical recording devices inside the brain called intracranial electrodes. The four participants reported their pain levels three to four times a day, after which their neural activity was immediately recorded with the electrodes. Using these methods, the researchers found that brain activity from specific regions in the brain called the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC) could predict the state of pain a person was in, i.e. the severity of their chronic pain. The predictive potential of activity in these brain regions may provide a so-called biomarker of chronic pain which could be of interest to many areas of clinical intervention, including diagnosis, treatment selection, and tracking prognosis in patients.

Chronic pain and depression
Crucially, chronic pain is a topic of research not to be investigated in isolation – an important comorbidity of chronic pain is depression. It is estimated that more than half of the people suffering from chronic pain experience depressive symptoms. A different study published in the same month highlighted this urgent need for neuroscientific research to investigate these two clinical conditions together; when investigating emotional brain function and levels of depressive symptoms in adults who either did or did not experience chronic pain, they found fundamentally different brain signatures between these groups. Whereas increased depressive symptoms in the group without pain were associated with increased coupling between the right amygdala and medial prefrontal cortex (mPFC), adults experiencing higher levels of depressive symptoms as well as chronic pain had neural signatures in the opposite direction, i.e. decreased coupling between these exact brain regions. Of note, medication use was not accounted for, so the potential medication effects on brain function still need to be disentangled. Nonetheless, their findings have provided an incentive for scientists to explore whether we may need to understand depressive symptoms fundamentally differently in those with chronic pain compared to those without. The same may be true when considering chronic pain in the brains of those with and without depressive symptoms. Therefore, it is crucial that the neural signatures of chronic pain reported in the Californian study are investigated in a population with comorbid depression, given that no participants included in their study had untreated depression. If research into the neural changes associated with chronic pain does not incorporate the severity of depression in patients, we may be overlooking a major part of the population with a chronic pain syndrome.