The human brain is an amazingly plastic organ that is shaped by the powerful experience of pain. Previous research has indicated that patients with chronic pain show reduced cerebral gray matter in areas related to the anticipation, experience, and transmission of pain. More recently, studies have shown the changes to be reversible: Patients with arthritis or low back pain underwent a turnaround of gray matter loss after surgical treatment eased their pain.
A new study reported in The Journal of Pain in October provides long overdue evidence that psychotherapy, one of the least invasive treatments for chronic pain—in particular, cognitive behavioral therapy (CBT)—can also produce measurable changes in cerebral gray matter volume and density that correlate with patients’ recovery. The study was led by Magdalena Naylor, a psychiatrist and neuroscientist at the University of Vermont, Burlington, US, and involved collaborators from the University of Maryland, Baltimore, US, and Duke University, Durham, North Carolina, US.
This new study “is the first documented study that shows cognitive behavioral therapy in a group setting is capable of changing the brain structure in patients with chronic pain,” said Naylor.
In 2011, David Seminowicz (the first author on the new study) and coworkers reported that patients with chronic low back pain experienced a normalization in gray matter thickness in the area of the left dorsolateral prefrontal cortex after surgical intervention that decreased their pain (Seminowicz et al., 2011). Their work followed a previous study by Arne May and colleagues at the University of Hamburg, Germany, showing a rebound in gray matter after successful hip replacement in people with chronic pain from arthritis (Rodriquez-Raecke et al., 2009).
In the new work, Naylor and her team devised a study to assess changes in cerebral gray matter in 13 patients after 11 weeks of group CBT. All of the subjects experienced chronic musculoskeletal pain of differing origins for an average of nine years. The team conducted magnetic resonance imaging scans and measured gray matter volume using voxel-based morphometry before and after CBT treatment. For comparison, they also scanned 13 healthy age-matched control subjects.
After their treatment, the patients exhibited an increase in gray matter in their dorsolateral prefrontal, posterior parietal, subgenual anterior cingulate/orbitofrontal and sensorimotor cortices, in addition to the hippocampus. Their cerebral gray matter also showed a decrease in the left supplementary motor areas.
These structural changes were consistent with the clinical outcomes of CBT, said Naylor. In CBT, patients are coached to identify and diminish pain catastrophizing—a hallmark of chronic pain in which patients anticipate the worst about incoming or ongoing pain—and taught to practice relaxation for better stress and pain control. The increase in gray matter reflects an improvement in the modulation of pain, or better mental or emotional assessment of their pain, suggested the research team. Changes in sensory and motor areas possibly reflect treatment-induced adaptation to continuous nociceptive signals, the corollary of which is the diversion of attention from pain emphasized in CBT.
In parallel, the researchers assessed the patients’ pain by using a modified variant of the Short Form McGill Pain Questionnaire and the Pain Symptoms subscale from the Treatment Outcomes in Pain Survey. Before CBT, the typical pain for the 13 patients averaged 6.3 on a zero to 10 scale, compared to a 5.3 after treatment. The patients also demonstrated increased control of pain and a reduction in catastrophizing.
Importantly, the decrease in pain catastrophizing, a central facet of CBT, was the clinical measure most strongly associated with changes in gray matter, specifically, increases in the secondary and primary somatosensory cortices, left dorsolateral prefrontal cortex, inferior frontal gyrus, and in the bilateral pregenual anterior cingulate cortex/medial prefrontal cortex.
“I think this gives me and other physicians and psychologists ammunition to recommend this kind of treatment; it’s not only clinical, but those clinical outcomes are correlated with physical changes in the brain,” said Naylor.
Interestingly, the team did not find any significant difference in gray matter between the patients before CBT treatment and control subjects, as other researchers have reported (see recent review by Bushnell et al., 2013). They believe this to be a result of their small sample size. In addition, they point out that different types of chronic pain might induce signature changes in the brain, as Apkarian and colleagues have demonstrated (Baliki et. al., 2011). In the current study, Naylor and colleagues studied 13 patients who had chronic pain of differing origins as opposed to a unitary type of chronic pain.
The authors propose that this gray matter gain represents an adaptation rather than a return to normal levels. In most of the areas that increased in gray matter, the increase was beyond what control subjects normally exhibited.
What underlies fluctuations in gray matter during the course of chronic pain and its successful treatment is still unknown. May, whose team demonstrated the reversal of gray matter changes in hip replacement patients, has suggested that since a decrease in gray matter is at least partially reversible with intervention, it is a consequence of, not the cause of, chronic pain. He is interested in the longevity of the structural changes Naylor’s team found. “What happens to the pain when these patients stop training?” May asked in an email. The crux of the matter is the question of causality: Did CBT decrease pain, therefore producing a change in gray matter, or did CBT increase gray matter, producing a change in pain perception?
Naylor said her team is currently conducting a longer study that she hopes will eventually address May’s inquiries. However, what is happening at the cellular level when the gray matter changes is an area needing much more research.
This study “can be very helpful for physicians who are treating patients with chronic pain to be more serious about referring them for psychotherapy, like cognitive behavioral therapy,” said Naylor.
Still, she believes each approach of pain management has its place in the clinical setting, from surgery to psychotherapy. “There are many ways of using cognitive behavioral therapy for pain in addition to surgical procedures and medications,” she said, “for a more holistic approach.”
Abdul-Kareem Ahmed is a medical student and freelance science writer in Providence, Rhode Island, US.
