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Resting-sate functional reorganization of the rat limbic system following neuropathic injury.

Baliki MN, Chang PC, Baria AT, Centeno MV, Apkarian AV - Sci Rep (2014)

Bottom Line: Similar to the human, the rat brain topological properties exhibited small world features and did not differ between SNI and sham.Twenty-eight days after SNI, functional connection changes were localized mainly to within the limbic system, as well as between the limbic and nociceptive systems.Furthermore, these changes were lateralized and in proportion to the tactile allodynia exhibited by SNI animals.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

ABSTRACT
Human brain imaging studies from various clinical cohorts show that chronic pain is associated with large-scale brain functional and morphological reorganization. However, how the rat whole-brain network is topologically reorganized to support persistent pain-like behavior following neuropathic injury remains unknown. Here we compare resting state fMRI functional connectivity-based whole-brain network properties between rats receiving spared nerve injury (SNI) vs. sham injury, at 5 days (n = 11 SNI; n = 12 sham) and 28 days (n = 11 SNI; n = 12 sham) post-injury. Similar to the human, the rat brain topological properties exhibited small world features and did not differ between SNI and sham. Local neural networks in SNI animals showed minimal disruption at day 5, and more extensive reorganization at day 28 post-injury. Twenty-eight days after SNI, functional connection changes were localized mainly to within the limbic system, as well as between the limbic and nociceptive systems. No connectivity changes were observed within the nociceptive network. Furthermore, these changes were lateralized and in proportion to the tactile allodynia exhibited by SNI animals. The findings establish that SNI is primarily associated with altered information transfer of limbic regions and provides a novel translational framework for understanding brain functional reorganization in response to a persistent neuropathic injury.

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Changes in hippocampus connectivity to sensorimotor and striatal regions reflect tactile allodynia behavior in SNI.Connectivity strength changes in (a) hippocampus-sensorimotor and (b) hippocampus–striatum connectivity between SNI and sham at day 28. Bar graphs represent the average ratio of the total number of significant connections (at link density = 0.1) relative to the total number of all possible connections between the regions. Scatter plots show the relationship between connectivity strength and tactile sensitivity thresholds of the injured paw in sham (black circles) and SNI (gray circles) animals. Error bars represent S.D. (*p<0.05, **p<0.01, two-sided unpaired t-test).
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f5: Changes in hippocampus connectivity to sensorimotor and striatal regions reflect tactile allodynia behavior in SNI.Connectivity strength changes in (a) hippocampus-sensorimotor and (b) hippocampus–striatum connectivity between SNI and sham at day 28. Bar graphs represent the average ratio of the total number of significant connections (at link density = 0.1) relative to the total number of all possible connections between the regions. Scatter plots show the relationship between connectivity strength and tactile sensitivity thresholds of the injured paw in sham (black circles) and SNI (gray circles) animals. Error bars represent S.D. (*p<0.05, **p<0.01, two-sided unpaired t-test).

Mentions: The hippocampus exhibited the strongest changes in functional connectivity between SNI and sham groups at day 28. Here we examined whether these connectivity changes are related to the increased mechanical sensitivity in the SNI group. The connectivity strength of the hippocampus to sensorimotor regions and the striatum was computed as the ratio of the total number of significant connections relative to the total number of all possible connections. In agreement with our initial observations (see Fig. 3), the hippocampus in SNI animals showed significantly increased connectivity to the striatum (mean ± S.D. for SNI = 0.13 ± 0.07; sham = 0.07 ± 0.04; t-value = 2.34, p <0.05), and decreased connectivity to sensorimotor cortex (SNI = 0.04 ± 0.01; sham = 0.09 ± 0.05; t-value = 2.98, p <0.01) at day 28 (Fig. 5). More importantly, these changes in functional connectivity correlated with the decreased mechanical thresholds in the SNI, but not the sham group. The hippocampus connectivity to the striatum showed a strong inverse correlation to paw withdrawal thresholds in the SNI group (r = −0.59, p = 0.05), whereas hippocampal connectivity to sensorimotor regions showed a positive correlation (r = 0.58, p = 0.06). On the other hand, sham animals showed no significant correlation of tactile threshold with hippocampus - striatum connectivity (r = 0.11, p = 0.75), nor with hippocampus-sensorimotor connectivity (r = 0.05, p = 0.89) (Fig 5).


Resting-sate functional reorganization of the rat limbic system following neuropathic injury.

Baliki MN, Chang PC, Baria AT, Centeno MV, Apkarian AV - Sci Rep (2014)

Changes in hippocampus connectivity to sensorimotor and striatal regions reflect tactile allodynia behavior in SNI.Connectivity strength changes in (a) hippocampus-sensorimotor and (b) hippocampus–striatum connectivity between SNI and sham at day 28. Bar graphs represent the average ratio of the total number of significant connections (at link density = 0.1) relative to the total number of all possible connections between the regions. Scatter plots show the relationship between connectivity strength and tactile sensitivity thresholds of the injured paw in sham (black circles) and SNI (gray circles) animals. Error bars represent S.D. (*p<0.05, **p<0.01, two-sided unpaired t-test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4151103&req=5

f5: Changes in hippocampus connectivity to sensorimotor and striatal regions reflect tactile allodynia behavior in SNI.Connectivity strength changes in (a) hippocampus-sensorimotor and (b) hippocampus–striatum connectivity between SNI and sham at day 28. Bar graphs represent the average ratio of the total number of significant connections (at link density = 0.1) relative to the total number of all possible connections between the regions. Scatter plots show the relationship between connectivity strength and tactile sensitivity thresholds of the injured paw in sham (black circles) and SNI (gray circles) animals. Error bars represent S.D. (*p<0.05, **p<0.01, two-sided unpaired t-test).
Mentions: The hippocampus exhibited the strongest changes in functional connectivity between SNI and sham groups at day 28. Here we examined whether these connectivity changes are related to the increased mechanical sensitivity in the SNI group. The connectivity strength of the hippocampus to sensorimotor regions and the striatum was computed as the ratio of the total number of significant connections relative to the total number of all possible connections. In agreement with our initial observations (see Fig. 3), the hippocampus in SNI animals showed significantly increased connectivity to the striatum (mean ± S.D. for SNI = 0.13 ± 0.07; sham = 0.07 ± 0.04; t-value = 2.34, p <0.05), and decreased connectivity to sensorimotor cortex (SNI = 0.04 ± 0.01; sham = 0.09 ± 0.05; t-value = 2.98, p <0.01) at day 28 (Fig. 5). More importantly, these changes in functional connectivity correlated with the decreased mechanical thresholds in the SNI, but not the sham group. The hippocampus connectivity to the striatum showed a strong inverse correlation to paw withdrawal thresholds in the SNI group (r = −0.59, p = 0.05), whereas hippocampal connectivity to sensorimotor regions showed a positive correlation (r = 0.58, p = 0.06). On the other hand, sham animals showed no significant correlation of tactile threshold with hippocampus - striatum connectivity (r = 0.11, p = 0.75), nor with hippocampus-sensorimotor connectivity (r = 0.05, p = 0.89) (Fig 5).

Bottom Line: Similar to the human, the rat brain topological properties exhibited small world features and did not differ between SNI and sham.Twenty-eight days after SNI, functional connection changes were localized mainly to within the limbic system, as well as between the limbic and nociceptive systems.Furthermore, these changes were lateralized and in proportion to the tactile allodynia exhibited by SNI animals.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

ABSTRACT
Human brain imaging studies from various clinical cohorts show that chronic pain is associated with large-scale brain functional and morphological reorganization. However, how the rat whole-brain network is topologically reorganized to support persistent pain-like behavior following neuropathic injury remains unknown. Here we compare resting state fMRI functional connectivity-based whole-brain network properties between rats receiving spared nerve injury (SNI) vs. sham injury, at 5 days (n = 11 SNI; n = 12 sham) and 28 days (n = 11 SNI; n = 12 sham) post-injury. Similar to the human, the rat brain topological properties exhibited small world features and did not differ between SNI and sham. Local neural networks in SNI animals showed minimal disruption at day 5, and more extensive reorganization at day 28 post-injury. Twenty-eight days after SNI, functional connection changes were localized mainly to within the limbic system, as well as between the limbic and nociceptive systems. No connectivity changes were observed within the nociceptive network. Furthermore, these changes were lateralized and in proportion to the tactile allodynia exhibited by SNI animals. The findings establish that SNI is primarily associated with altered information transfer of limbic regions and provides a novel translational framework for understanding brain functional reorganization in response to a persistent neuropathic injury.

Show MeSH
Related in: MedlinePlus