Open AccessAdaptive alterations in the mesoaccumbal network after peripheral nerve injury
Author(s) -
Wei Ren,
Maria Virginia Centeno,
Xu-Hong Wei,
Ian R. Wickersham,
Marco Martina,
A. Vania Apkarian,
D. James Surmeier
Publication year - 2020
Publication title -
pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.524
H-Index - 258
eISSN - 1872-6623
pISSN - 0304-3959
DOI - 10.1097/j.pain.0000000000002092
Subject(s) - ventral tegmental area , sni , nucleus accumbens , neuroscience , nerve injury , dopaminergic , basolateral amygdala , neuropathic pain , chronic pain , infralimbic cortex , medium spiny neuron , medicine , optogenetics , amygdala , dopamine , psychology , prefrontal cortex , biology , striatum , biochemistry , cognition , hydrolysis , acid hydrolysis
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.