Brain gray matter decrease in chronic pain is the consequence and not the cause of pain

Abstract

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.

Figures

Figure 1.

Statistical parametric maps demonstrating the structural difference in gray matter in patients with chronic pain due to primary hip OA (not flipped). Significant gray matter changes are shown superimposed in color (decrease of gray matter) on a normalized image of a healthy control subject. The left side of the picture is the left side of the brain. A, Significant decrease of gray matter between patients with chronic pain due to primary hip OA and unaffected control subjects. B, Gray matter increase in 10 pain-free patients at the third scanning period 16–18 weeks after total hip replacement surgery, compared with the first (preoperative) and second (6 weeks postsurgery) scans.

Figure 2.

Gray matter changes in the longitudinal group (n = 10) between the first two scans (before the operation and 6–8 weeks after the operation) with the third scan (pain free 16–18 weeks after the operation). Each box plot represents relative gray matter percentage signal change over time and 90% confidence interval (gray line) averaged over the cluster of the dorsolateral prefrontal cortex (A), amygdala (B), S2 cortex (C), insular cortex (D), brainstem (E), and anterior cingulate cortex (F). C.I., Confidence interval.