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Papers of the Week

Papers: 22 Jan 2022 - 28 Jan 2022

Animal Studies

2022 Jan 25


Reversal of neuropathic pain is associated with corticostriatal functional reorganization after nerve repair in the spared nerve injury model.


Bao Q-Y, Chang P-C, Centeno M V, Farmer MA, Baliki M, Procissi D, Zhang W, Apkarian VA
Pain. 2022 Jan 25.
PMID: 35082247.


Following surgical repair after peripheral nerve injury, neuropathic pain diminishes in most patients, but can persist in a small proportion of cases the mechanism of which remains poorly understood. Based on the spared nerve injury (SNI), we developed a rat nerve repair (NR) model, where a delayed reconstruction of the SNI injured nerves resulted in alleviating chronic pain-like behavior only in a subpopulation of rats. Multiple behavioral measures were assayed over 11-week pre- and post-surgery periods (tactile allodynia, pain prick responses, sucrose preference, motor coordination, cold allodynia) in SNI (n=10), sham (n=8), and NR (n=12) rats. All rats also underwent resting-state- fMRI under anesthesia at multiple timepoints post-surgery, and at 10-weeks histology and retrograde labeling was used to calculate peripheral reinnervation. Behavioral measures indicated that at about 5-weeks post-surgery the NR group separated to pain persisting (NR-persisting, n=5) and recovering groups (NR-recovering, n=7). Counts of afferent nerves and of DRG cells were not different between NR groups. Therefore, NR group differences could not be explained by peripheral reorganization. In contrast, large brain functional connectivity differences were observed between NR groups, where corticolimbic reorganization paralleled with pain recovery (repeat measure ANOVA, false discovery rate, p <0.05), and functional connectivity between accumbens and medial frontal cortex was related both to tactile allodynia (nociception) and to sucrose preference (anhedonia) in NR group. Our study highlights the importance of brain circuitry in the reversal of neuropathic pain as a natural pain-relieving mechanism. Further studies regarding the therapeutic potentials of these processes are warranted.