Pain sensitivity is inversely related to regional grey matter density in the brain

Nichole M. Emerson, Fadel Zeidan, Oleg V. Lobanov, Morten S. Hadsel, Katherine T. Martucci, Alexandre S. Quevedo, Christopher J. Starr, Hadas Nahman-Averbuch, Irit Weissman-Fogel, Yelena Granovsky, David Yarnitsky, Robert C. Coghill
Published on-line in PAIN, December 2013

Pain is an extremely personal experience that varies substantially among individuals. In a study created at Wake Forest School of Medicine and printed in the December 2013 issue of brain-image-577x796PAIN, a group of scientists investigated the relationship between grey matter density across the whole brain and interindividual differences in pain sensitivity in 116 healthy volunteers (62 women and 54 men). 

Voxel-based morphometry (VBM) was used to map the brain and record variances.  VBM is a neuroimaging analysis technique that allows investigation of focal differences in brain anatomy, using the statistical approach of statistical parametric mapping. Voxel, or volume element, represents a value on a regular grid in three dimensional space.   In traditional morphometry, volume of the whole brain or its subparts is measured by drawing regions of interest (ROIs) on images from MRI brain scanning and calculating the volume enclosed. However, this is time consuming and can only provide measures of rather large areas. Smaller differences in volume may be overlooked. VBM registers every brain to a template, which gets rid of most of the large differences in brain anatomy among people. Then the brain images are smoothed so that each voxel represents the average of itself and its neighbors.

Finally, the image volume is compared across brains at every voxel.  Structural magnetic resonance imaging (MRI) and psychophysical data from 10 previous functional MRI studies were used.  Age, sex, unpleasantness ratings, scanner sequence, and sensory testing location were added to the model as covariates. Regression analysis of grey matter density across the whole brain and thermal pain intensity ratings at 49°C revealed a significant inverse relationship between pain sensitivity and grey matter density in bilateral regions of the posterior cingulate cortex, precuneus, intraparietal sulcus, and inferior parietal lobule. Unilateral regions of the left primary somatosensory cortex also exhibited this inverse relationship. No regions showed a positive relationship to pain sensitivity. These structural variations occurred in areas associated with the default mode network, attentional direction and shifting, as well as somatosensory processing. These findings underscore the potential importance of processes related to default mode thought and attention in shaping individual differences in pain sensitivity and indicate that pain sensitivity can potentially be predicted on the basis of brain structure.

A recently published Medscape article by Sue Hughes details an overview of this study discussing that an individual's sensitivity to pain appears to be related to the amount of grey matter in certain regions of the brain.  In her article she quotes senior author of the study, Robert Coghill, PhD, Wake Forest Baptist Medical Center, commenting to Medscape Medical News, "This is the first time that a relationship has been shown between pain sensitivity and brain structure. This initial discovery adds to our basic understanding of brain mechanisms and could lead to clinical implications in pain management."

To set up a measurement protocol for this study, researchers analyzed data from 10 previous studies in which 116 participants underwent the same sensory test.  Pain intensity of participants was rated when a small spot of skin on their arm or leg was heated to 120 degrees Fahrenheit, followed by MRI of the brain 2 days later.  The researchers were not looking for brain activity related to the stimulus at the time of delivery, but were looking for more structural variations that would have been in place for a long time.  They wanted to investigate the relationship between pain sensitivity and brain structure. Particularly, is there anything in the resting brain structure, when it is not experiencing pain, which can tell scientists how sensitive an individual may be to pain? Study results identified that individuals with higher pain intensity ratings had less grey matter in the posterior cingulate cortex, precuneus, and areas of the posterior parietal cortex — areas of the brain that contribute to internal thoughts and control of attention.  Interestingly, it was discovered that these specific areas are part of the default mode network; a set of connected brain regions that are associated with the free-flowing thoughts that people have while they are daydreaming.  According to Dr. Coghill, the researchers believe that default-mode activity may compete with brain activity that generates an experience of pain, such that individuals with high default-mode activity would have reduced sensitivity to pain.  The study revealed that there is a competition in a person’s head between pain or other things being thought about, which can be like a double-edged sword.  A person needs to know when they are in acute pain.  For instance, if you touch something hot, you need to feel pain so that you remove your hand.  But in the case of chronic pain, attention to the pain may make it intensify.

Attention is another important role of the default mode network and the study showed that individuals who can best keep their attention focused may also be best at keeping pain under control.  If a person is preoccupied with something else, that though pattern can overrule other things.  Dr. Coghill noted that in a previous Canadian study, it was shown that individuals who stay on task do not have pain interfere so much.  

Results of this study suggest that structural differences found by the researchers could provide a foundation for development of better tools for diagnosis, classification, treatment and even prevention of pain.

Based on study information, pain is very good at getting our attention; but it may also be possible to change a person’s sensitivity to pain by practicing directing thoughts elsewhere.  Meditation and mindfulness training, in which a person learns how to better control thoughts, have been shown to be associated with a remarkable reduction in pain intensity.  Additionally, Dr. Coghill noted that individuals who have meditated over the long term have been shown to have more grey matter in certain areas, indicating that it seems possible to build up grey matter, and train the brain to be less sensitive to pain.
 
Besides treatment implications for chronic pain, this study may also have implications for individualization of treatments for acute pain.  "Certain patients who are less sensitive to pain may currently be over medicated, causing unnecessary side effects and risks for addiction," Dr. Coghill explained. "If we can identify these patients we can minimize their medication doses, and give higher doses to those who need it the most. The grey matter in the default-mode network may be the factor to measure to determine how much painkiller or anesthetic is needed."