Structural Brain Alterations in Community Dwelling Individuals with Chronic Joint Pain

Abstract

Background and purpose: Central sensitization in chronic pain involves structural brain changes that influence vulnerability to pain. Identifying brain regions involved in pain processing and sensitization can provide more insight into chronic pain. This study examines structural brain changes in chronic pain and experimental pain in a large population-based study.

Materials and methods: For 3892 participants in the Rotterdam study, global and regional MR imaging brain volumes were automatically segmented and quantified. Chronic joint pain was defined as pain for more than half of all days during the past 6 weeks. Heat pain thresholds were measured in a subset of 1538 individuals. The association between the presence of chronic joint pain and global and lobar brain volumes was studied. Subsequently, literature was reviewed and the association of chronic pain and heat pain thresholds with 11 brain regions associated with musculoskeletal pain in previous publications was studied.

Results: Total gray matter volume was smaller in women with chronic pain (β = -0.066, P = .016). This effect was primarily driven by lower gray matter volume in the temporal lobe (β = 0.086, P = .005), the frontal lobe (β = -0.060, P = .039), and the hippocampus (β = -0.099, P = .002). In addition, we observed that a lower heat pain threshold was associated with smaller volumes of the hippocampus (β = 0.017, P = .048), the thalamus (β = 0.018, P = .009), and the anterior cingulate cortex (β = -0.016, P = .037). In men, no significant associations were observed.

Conclusions: The primary identified brain areas, the temporal and frontal lobes and the hippocampus, indicated involvement of emotional processing. The volumetric differences found indicated a sex-specific neuroplasticity in chronic pain. These results emphasized sex-specific and multidisciplinary pain treatment.

© 2016 by American Journal of Neuroradiology.

Figures

Fig 1.

Chronic musculoskeletal pain and global brain volumes. Analyses adjusted for age, intracranial volume and depression. β is the difference in standardized brain volume for individuals with chronic joint pain compared with those without chronic joint pain.

Fig 2.

Brain volumes in regions of the limbic system and signal processing in relation to chronic musculoskeletal pain in (A) female and (B) male subjects. Plots represent β and standard error. β is the difference in standardized brain volume for individuals with chronic joint pain compared with those without chronic joint pain. Analyses were adjusted for age, intracranial volume, and depression. *P = .002. Thal indicates thalamus; Hippo, hippocampus; Amyg, amygdala; OFC, orbitofrontal cortex; vlPFC, ventrolateral prefrontal cortex; dlPFC, dorsolateral prefrontal cortex; PCC, posterior cingulate cortex; MCC, midcingulate cortex; ACC, anterior cingulate cortex; Insula, insular cortex; S1, primary somatosensory cortex.

Fig 3.

Quantitative sensory testing (heat pain threshold) and structural brain alterations in (A) female and (B) male subjects. Plots represent β and standard error. β is the difference in standardized brain volume per degree of temperature (Celsius); analyses were adjusted for age, intracranial volume, and depression. *P < .05. Thal indicates thalamus; Hippo, hippocampus; Amyg, amygdala; OFC, orbitofrontal cortex; vlPFC, ventrolateral prefrontal cortex; dlPFC, dorsolateral prefrontal cortex; PCC, posterior cingulate cortex; MCC, midcingulate cortex; ACC, anterior cingulate cortex; Insula, insular cortex; S1, primary somatosensory cortex.