Inflammatory Pain Alters Dopaminergic Modulation of Excitatory Synapses in the Anterior Cingulate Cortex of Mice

Pain modulation of dopamine-producing nuclei is known to contribute to the affective component of chronic pain. However, pain modulation of pain-related cortical regions receiving dopaminergic inputs is understudied. The present study demonstrates that mice with chronic inflammatory injury of the hind paws develop persistent mechanical hypersensitivity and transient anxiety. Peripheral inflammation induced by injection of complete Freund's Adjuvant (CFA) induced potentiation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor (AMPAR) currents with a presynaptic component in layer of the ACC. After four days of inflammatory pain, the dopamine-mediated inhibition of AMPAR currents was significantly reduced in the ACC. Furthermore, dopamine enhanced presynaptic modulation of excitatory transmission, but only in mice with inflammatory pain. High-performance liquid chromatography (HPLC) analysis of dopamine tissue concentration revealed that dopamine neurotransmitter concentration in the ACC was reduced three days following CFA. Our results demonstrate that inflammatory pain induces activity-dependent changes in excitatory synaptic transmission and alters dopaminergic homeostasis in the ACC. (C) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

The study demonstrates that chronic inflammatory injury leads to mechanical hypersensitivity and transient anxiety. Inflammatory pain induces alterations in dopaminergic inputs and excitatory transmission in pain-related cortical regions.