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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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Global topological features are similar between sham and SNI at 5 and 28 days after injury.(a) Tactile sensitivity threshold of the injured paw in two groups of SNI and sham animals, day 5 (sham: n = 12, SNI: n = 11) and day 28 (sham: n = 12, SNI: n = 11) post-injury. Both SNI groups exhibited decreased mechanical threshold compared to sham animals. (b) Colored regions represent anatomically parcellated ROIs (n = 96; Table 1). Distance to bregma (in mm) is labeled at the bottom of each slice.(c–g) Topological features including, clustering coefficient, global efficiency, modularity, betweenness centrality, and small-worldness, were similar between SNI and sham animals at both time points post injury. Groups and time differences were evaluated using a two-way ANOVA. (h) Degree distribution, the probability distribution of the degree of a node in the network of sham (black) and SNI (gray) animals 5 and 28 days following injury. Error bars represent S.D. (*p<0.05, ** p<0.01, Tukey post-hoc test).
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f1: Global topological features are similar between sham and SNI at 5 and 28 days after injury.(a) Tactile sensitivity threshold of the injured paw in two groups of SNI and sham animals, day 5 (sham: n = 12, SNI: n = 11) and day 28 (sham: n = 12, SNI: n = 11) post-injury. Both SNI groups exhibited decreased mechanical threshold compared to sham animals. (b) Colored regions represent anatomically parcellated ROIs (n = 96; Table 1). Distance to bregma (in mm) is labeled at the bottom of each slice.(c–g) Topological features including, clustering coefficient, global efficiency, modularity, betweenness centrality, and small-worldness, were similar between SNI and sham animals at both time points post injury. Groups and time differences were evaluated using a two-way ANOVA. (h) Degree distribution, the probability distribution of the degree of a node in the network of sham (black) and SNI (gray) animals 5 and 28 days following injury. Error bars represent S.D. (*p<0.05, ** p<0.01, Tukey post-hoc test).

Mentions: Consistent with previous observations31, SNI animals exhibited decreased mechanical thresholds (tactile allodynia) of the injured (left) paw compared to sham at days 5 and 28 post-injury (F1,39 = 85.08, p < 0.001). Additionally, there was no effect of time (F1,39 = 1.09, p = 0.30) nor a group by time interaction (F1,39 = 0.95, p = 0.35). Differences between SNI and sham thresholds at days 5 and 28 post-injury were further assessed using Tukey post-hoc analysis. SNI animals showed significant differences in mechanical threshold of the injured paw at day 5 (mean ± S.D. for SNI = 1.90 ± 0.74; sham = 7.84 ± 0.68; p < 0.0001) and at day 28 (SNI = 0.46 ± 0.71; sham = 7.78 ± 0.74; p < 0.0001) post-injury. There was no significant within-group difference in mechanical threshold of the injured paw in SNI animals at days 5 and 28 post-injury (p = 0.51) (Fig. 1a). Finally, SNI animals showed no significant group effect (F1,39 = 1.51, p = 0.23), time effect (F1,39 = 1.17, p = 0.29), nor group by time interaction (F1,39 = 0.78, p = 0.38) in the mechanical thresholds of the uninjured (right) paw.


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)

Global topological features are similar between sham and SNI at 5 and 28 days after injury.(a) Tactile sensitivity threshold of the injured paw in two groups of SNI and sham animals, day 5 (sham: n = 12, SNI: n = 11) and day 28 (sham: n = 12, SNI: n = 11) post-injury. Both SNI groups exhibited decreased mechanical threshold compared to sham animals. (b) Colored regions represent anatomically parcellated ROIs (n = 96; Table 1). Distance to bregma (in mm) is labeled at the bottom of each slice.(c–g) Topological features including, clustering coefficient, global efficiency, modularity, betweenness centrality, and small-worldness, were similar between SNI and sham animals at both time points post injury. Groups and time differences were evaluated using a two-way ANOVA. (h) Degree distribution, the probability distribution of the degree of a node in the network of sham (black) and SNI (gray) animals 5 and 28 days following injury. Error bars represent S.D. (*p<0.05, ** p<0.01, Tukey post-hoc test).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Global topological features are similar between sham and SNI at 5 and 28 days after injury.(a) Tactile sensitivity threshold of the injured paw in two groups of SNI and sham animals, day 5 (sham: n = 12, SNI: n = 11) and day 28 (sham: n = 12, SNI: n = 11) post-injury. Both SNI groups exhibited decreased mechanical threshold compared to sham animals. (b) Colored regions represent anatomically parcellated ROIs (n = 96; Table 1). Distance to bregma (in mm) is labeled at the bottom of each slice.(c–g) Topological features including, clustering coefficient, global efficiency, modularity, betweenness centrality, and small-worldness, were similar between SNI and sham animals at both time points post injury. Groups and time differences were evaluated using a two-way ANOVA. (h) Degree distribution, the probability distribution of the degree of a node in the network of sham (black) and SNI (gray) animals 5 and 28 days following injury. Error bars represent S.D. (*p<0.05, ** p<0.01, Tukey post-hoc test).
Mentions: Consistent with previous observations31, SNI animals exhibited decreased mechanical thresholds (tactile allodynia) of the injured (left) paw compared to sham at days 5 and 28 post-injury (F1,39 = 85.08, p < 0.001). Additionally, there was no effect of time (F1,39 = 1.09, p = 0.30) nor a group by time interaction (F1,39 = 0.95, p = 0.35). Differences between SNI and sham thresholds at days 5 and 28 post-injury were further assessed using Tukey post-hoc analysis. SNI animals showed significant differences in mechanical threshold of the injured paw at day 5 (mean ± S.D. for SNI = 1.90 ± 0.74; sham = 7.84 ± 0.68; p < 0.0001) and at day 28 (SNI = 0.46 ± 0.71; sham = 7.78 ± 0.74; p < 0.0001) post-injury. There was no significant within-group difference in mechanical threshold of the injured paw in SNI animals at days 5 and 28 post-injury (p = 0.51) (Fig. 1a). Finally, SNI animals showed no significant group effect (F1,39 = 1.51, p = 0.23), time effect (F1,39 = 1.17, p = 0.29), nor group by time interaction (F1,39 = 0.78, p = 0.38) in the mechanical thresholds of the uninjured (right) paw.

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