Shifting brain circuits in pain chronicity

Abstract

The evaluation of brain changes to a specific pain condition in pediatric and adult patients allows for insights into potential mechanisms of pain chronicity and possibly long-term brain changes. Here we focused on the primary somatosensory system (SS) involved in pain processing, namely the ventroposterolateral thalamus (VPL) and the primary somatosensory cortex (SI). We evaluated, using MRI, three specific processes: (a) somatotopy of changes in the SS for different pain origins (viz., foot vs. arm); (b) differences in acute (ankle sprain versus complex regional pain syndrome-CRPS); and (c) differences of the effects of CRPS on SS in pediatric versus adult patients. In all cases, age- and sex-matched individuals were used as controls. Our results suggest a shift in concurrent gray matter density (GMD) and resting functional connectivity strengths (rFC) across pediatric and adult CRPS with (a) differential patterns of GMD (VPL) and rFC (SI) on SS in pediatric vs. adult patterns that are consistent with upper and lower limb somatotopical organization; and (b) widespread GMD alterations in pediatric CRPS from sensory, emotional and descending modulatory processes to more confined sensory-emotional changes in adult CRPS and rFC patterns from sensory-sensory alterations in pediatric populations to a sensory-emotional change in adult populations. These results support the idea that pediatric and adult CRPS are differentially represented and may reflect underlying differences in pain chronification across age groups that may contribute to the well-known differences between child and adult pain vulnerability and resilience.

Keywords: CRPS; S1; adult; arm; brain; complex regional pain; leg; nerve; pediatric; thalamus.

Figure 1

Whole brain gray matter density analysis between pediatric chronic versus acute. (a) Brain sites in which significantly reduced (cool color scale) or increased (warm color scale) gray matter density was observed in pediatric chronic pain as compared with patients with acute pain, overlaid onto axial, coronal and sagittal T1‐weighted anatomical image set. Slice locations are located on the top left of each image and are in Montreal Neurological Institute space. (b) Correlation between regional gray matter density values within these regions against pain intensity. Note that significant correlations were confined to brain sites associated with somatosensory related processing and modulation, that is, the ventral posterolateral nucleus of the thalamus and the thalamic reticular nucleus [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Plots of gray matter density values in patients (acute and chronic) and healthy controls. Note that these values were derived from overlaying significant clusters from the patient contrast previously described. Significant between‐group differences were determined using independent two‐sample t‐test (*p < .05). Note that the white horizontal line reflects the mean, whereas gray shading represents one standard deviation above and below, within each group [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Whole brain gray matter density analysis between adult chronic and healthy controls. (a) Regional gray matter density reduced within the ventral posterolateral thalamic nucleus (cool color bar) and increased within the anterior cingulate cortex (warm color bar) in adult chronic as compared with controls, overlaid onto an axial and coronal T1‐weighted anatomical image set. Slice locations are located on the top left of each image and are in Montreal neurological institute space. (b) Correlations between regional gray matter density values within these regions against pain intensity and disease duration. Note that no significant correlations were observed [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

Significant differences in seed‐based functional connectivity in pediatric (acute and chronic) and adult chronic as compared with controls. (a) Plots of resting seed‐based functional connectivity from orbitofrontal cortex cluster, derived from pediatric acute and chronic gray matter density analysis. Note that compared with controls, acute patients have significantly greater functional connectivity strengths between the orbitofrontal cortex and the hippocampus. (b) Plots of resting seed‐based functional connectivity from ventral posterolateral thalamic nucleus cluster, derived from pediatric chronic and healthy control gray matter density analysis. Note that compared with controls, pediatric chronic patients have significantly greater functional connectivity strengths between the ventral posterolateral thalamic nucleus and the primary motor and somatosensory cortex. (c) Plots of resting seed‐based functional connectivity from anterior cingulate cortex and ventral posterolateral thalamic nucleus clusters, derived from between adult chronic and healthy control gray matter density analysis. Note that compared with controls, adult chronic patients have significantly greater functional connectivity strengths between the anterior cingulate cortex and the primary somatosensory cortex, whereas ventral posterolateral thalamic nucleus had reduced connectivity with the posterior cingulate cortex. Note that no significant correlations were observed between these values and pain intensity or disease duration (p > .05) [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 5

Overlay of significant pediatric and adult chronic structural and functional clusters within the ventral posterolateral thalamic nucleus and the primary somatosensory cortex. (a) Altered gray matter density in the ventral posterolateral nucleus of the thalamus that are consistent with upper (adult) and lower (pediatric) limb somatotopy, that is, lateral to medial, respectively. Note that increased gray matter density in pediatric chronic patients was reported relative to both pediatric acute patients and healthy controls. (b) Altered resting functional connectivity strengths within the primary somatosensory cortex, consistent upper limb (anterolateral) and lower limb (posteromedial) somatotopic organization [Color figure can be viewed at http://wileyonlinelibrary.com]