D1 and D2 neurons in medial nucleus accumbens participate in chronic orofacial pain phenotypes.

Introduction: Trigeminal nerve injuries can lead to different outcomes, such as chronic neuropathic pain. Nevertheless, it is still elusive why different phenotypes of chronic pain development are shown among individuals. Nucleus accumbens (NAc) might be important for chronic pain development. Still, the role of this structure and its neural subpopulations on these phenotypes development in the orofacial region remains unknown. Objectives: To evaluate the role of dopamine D1- and D2-receptor-expressing neurons (D1Rn and D2Rn) of medial NAc (mNAc) in developing phenotypes of chronic orofacial pain. Methods: C57BL/6 male and female mice underwent a trigeminal nerve compression injury and were assessed with the von Frey test for nociceptive threshold on day 3 and from weeks 1 to 14. To determine the role of mNAc D1Rn and D2Rn, transgenic D1R-Cre and D2R-Cre mice were infected with a genetically engineered caspase, causing specific ablation of such neurons. Results: All the injured C57BL/6 mice showed mechanical hypersensitivity during the first weeks. On week 2, mice were classified into high and low threshold (HT and LT). Most HT mice recovered from mechanical hypersensitivity, whereas most LT mice remained hypersensitive during all assessment weeks. Both mNAc D1Rn and D2Rn ablation decreased the percentage of HT mice, and D2Rn ablation increased the time of hypersensitivity recovery, suggesting these populations participate in both nociceptive threshold profiles and recovery capacity. Conclusion: mNAc D1Rn and D2Rn might play an important role in determining the phenotypes of chronic orofacial pain development after a nervous injury.