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

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.