It now seems clear that the brain changes in patients with chronic pain problems. However, this is probably where the consensus ends as there is still much that remains unclear and speculative in this area. This elegant study by Rodriguez-Raecke and colleagues from the University of Hamburg (abstract at the end of this article) investigate two important questions regarding cortical changes in chronic pain. Firstly, are the observed brain changes reversible and secondly, are the changes a consequence of ongoing pain or causative of the chronic pain experience. To investigate these issues the researchers used voxel based morphometry to measure gray matter density in a group of patients with primary hip OA before and after hip replacement surgery. This is a particularly apt condition to study to help answer the first question as it is a chronic pain problem that is largely curable (the authors quote a figure of 88% of patients being pain free post total hip replacement). The suitability of this condition to answer the second question is less clear. Hip OA represents a chronic pain problem for which there is a clear and well understood peripheral cause. The chronic pain problems in which some authors have argued that brain changes are potentially causal do not demonstrate this characteristic. Problems such as complex regional pain syndrome, phantom pain, fibromyalgia and chronic back pain lack a clear demonstrable peripheral mechanism of symptom production, primarily why authors have looked to the brain for potential causal mechanisms.
So what did they find? The results of the brain scans of 32 hip OA patients taken before surgery were compared to the results from 32 age and gender matched healthy controls. This analysis confirmed that hip OA, like many other chronic pain problems, is associated with gray matter density changes in a number of locations. A subgroup of ten patients were scanned 16 – 18 weeks after surgery when they were completely pain free and the results of these scans compared to the pre surgery scans. A significant increase in gray matter density was seen in about half the brain regions that demonstrated gray matter loss prior to surgery.
So it seems that some of the observed brain changes are reversible, though it is notable that the density changes only recede in some brain areas. Also, it is not clear if gray matter density is restored to a level compatible with healthy controls, a comparison of the post operative scans with those of the healthy controls would have been an interesting addition to this study.
As is obvious from the title of the paper the authors suggest this result indicates that gray matter changes are a consequence of ongoing pain. This is certainly an appropriate interpretation of these findings, but I think some caution is warranted. As the authors point out, many things other than the removal of a peripheral nocicpetive generator have occurred in this group. There has probably been considerable social, activity and lifestyle change as well as investment in a treatment with strong positive expectations and considerable ritual. Also, as not all brain areas show a tendency to normalise it is possible that some of the areas that do not change represent pre onset values that could predispose the individual to the development of persistent pain [1,2] and so represent part of a causal mechanism of chronification. Finally, one thing that is not clear from the paper is why only ten patients were followed up. It would have been interesting to see the results of the whole cohort, particularly if there were patients who did not report complete pain relief after surgery.
Benedict Wand is Associate Professor at the School of Health Sciences, The University of Notre Dame
1. Gustin SM, Wrigley PJ, Siddall PJ, Henderson LA. Brain Anatomy Changes Associated with Persistent Neuropathic Pain Following Spinal Cord Injury. Cereb Cortex 2009; Oct 8. [Epub ahead of print]
2. Robinson J and Apkarian A. Low back pain. In: Mayer E and Bushnell C, (eds). Functional pain syndromes: presentation and pathophysiology Seattle: IASP press, 2009
Brain gray matter decrease in chronic pain is the consequence and not the cause of pain
Rodriguez-Raecke R, Niemeier A, Ihle K, Ruether W, May A.
Department of Systems Neuroscience and Orthopaedics, University Medical Center Hamburg Eppendorf, Hamburg, Germany
Recently, local morphologic alterations of the brain in areas ascribable to the transmission of pain were reported in patients suffering from chronic pain. Although some authors discussed these findings as damage or loss of brain gray matter, one of the key questions is whether these structural alterations in the cerebral pain-transmitting network precede or succeed the chronicity of pain. We investigated 32 patients with chronic pain due to primary hip osteoarthritis and found a characteristic gray matter decrease in patients compared with controls in the anterior cingulate cortex (ACC), right insular cortex and operculum, dorsolateral prefrontal cortex (DLPFC), amygdala, and brainstem. We then investigated a subgroup of these patients (n = 10) 6 weeks and 4 months after total hip replacement surgery, monitoring whole brain structure. After surgery, all 10 patients were completely pain free and we observed a gray matter increase in the DLPFC, ACC, amygdala, and brainstem. As gray matter decrease is at least partly reversible when pain is successfully treated, we suggest that the gray matter abnormalities found in chronic pain do not reflect brain damage but rather are a reversible consequence of chronic nociceptive transmission, which normalizes when the pain is adequately treated.
See the full article at J Neurosci. 2009 Nov 4;29(44):13746-50.
Benedict Wand (2009). Benedict Wand on Brain Changes in Chronic Pain BodyInMind