Data that were presented by Apkar Vania Apkarian, PhD, Northwestern University, Chicago, Illinois, USA, appear to demonstrate that chronic pain imparts a specific signature on the brain that is associated with functional, behavioral, and chemical changes in the cerebral cortex. The specificity of this pain signature for different clinical conditions may provide the opportunity to develop targeted therapies for osteoarthritis and other chronic painful conditions.

Dr. Apkarian reviewed a study that was conducted at Northwestern University in which painful pressure stimuli were applied to the knee of osteoarthritis (OA) patients and healthy controls and ratings of evoked pain and related brain activity were subsequently examined. In this study, the psychophysical pressure pain ratings and brain activation patterns of evoked pain were essentially the same between OA patients and healthy subjects and between knees with better and worse OA. In addition, the location of brain activity for evoked pain did not overlap the areas that were associated with continuous pain. However, brain activity that was related to pain scoring systems, such as the Western Ontario and McMaster Universities Osteoarthritis Index and the McGill Pain Questionnaire, mainly overlapped areas that were identified for chronic pain [Parks EL et al. Eur J Pain 2011].

Regional gray matter density studies indicate decreases in grey matter in specific regions of brain that are associated with chronic OA pain. There was also evidence for reversibility, whereby treatment may potentially undo grey matter decreases. In a recent, yet-to-be published study, Dr. Apkarian's group also examined brain anatomical changes in healthy patients compared with those who have chronic back pain, complex regional pain syndrome, or OA. Using Voxel-wise Voxel-based morphometry, the group examined how the brain reorganizes regionally in response to pain. They identified unique morphological signatures that are associated with the different types of chronic pain. Areas of brain interaction increased in chronic pain subjects, destroying spatial relationships. This was not apparent in healthy subjects. Whether pain was chronic versus acute determined the amount of time the brain required to reorganize into its new anatomical state.

Specificity of this signature for each clinical condition provides the opportunity to develop targeted therapies. In a double-blind, placebo-controlled brain imaging study in which chronic back pain subjects were treated with a 5% lidocaine patch or placebo, no difference in pain perception or brain activity was noted between the two groups at 2 weeks. However, when the subjects were regrouped into persisting pain (nonresponders) and decreasing pain (responders), it was possible to identify at baseline two functional connections in the brain that distinguish between persisting and decreasing chronic back pain and which can be used to predict which patients will respond to placebo. A pure placebo and brain imaging study found the same results in OA patients.

Using brain coordinates from a chronic back pain study, the investigators were able to identify a prefrontal circuit that differentiates and predicts placebo responders from nonresponders with >95% accuracy. Thus, there is a brain circuit that indicates which patients will be placebo responders. “The brain predicts the future, and this may be a critical tool for future decisions about the patient,” Dr. Apkarian concluded.