I am a
Home I AM A Search Login

Papers of the Week

Papers: 20 Feb 2021 - 26 Feb 2021

Animal Studies

2021 Mar 01




Editor's Pick

Adaptive alterations in the mesoaccumbal network after peripheral nerve injury.


Ren W, Centeno M V, Wei X, Wickersham I, Martina M, Apkarian VA, Surmeier JD
Pain. 2021 Mar 01; 162(3):895-906.
PMID: 33021562.


The nucleus accumbens (NAc) and the ventral tegmental area (VTA) are critical hubs in the brain circuitry controlling chronic pain. Yet, how these 2 regions interact to shape the chronic pain state is poorly understood. Our studies show that in mice, spared nerve injury (SNI) induced alterations in the functional connectome of D2-receptor expressing spiny projection neurons in the core region of the NAc-enhancing connections with prelimbic cortex and weakening them with basolateral amygdala. These changes, which were attributable in part to SNI-induced suppression of VTA dopaminergic signaling, were adaptive because mimicking them chemogenetically alleviated the anxiety and social withdrawal accompanying injury. By contrast, chemogenetic enhancement of activity in VTA dopaminergic neurons projecting to the medial shell of the NAc selectively suppressed tactile allodynia in SNI mice. These results suggest that SNI induces regionally specific alterations in VTA dopaminergic signaling in the NAc to promote environmental reengagement after injury. However, countervailing, homeostatic mechanisms limit these adaptive changes, potentially leading to the chronic pain state.