Optogenetic Activation of Dopamine Receptor D1 and D2 Neurons in Anterior Cingulate Cortex Differentially Modulates Trig
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ORIGINAL ARTICLE
Optogenetic Activation of Dopamine Receptor D1 and D2 Neurons in Anterior Cingulate Cortex Differentially Modulates Trigeminal Neuropathic Pain Sufang Liu 1,2 & Hui Shu 1 & Joshua Crawford 1 & Yajing Ma 1,2 & Changsheng Li 3 & Feng Tao 1,4 Received: 17 May 2020 / Accepted: 8 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Anterior cingulate cortex (ACC) is a critical brain center for chronic pain processing. Dopamine signaling in the brain has been demonstrated to contribute to descending pain modulation. However, the role of ACC dopamine receptors in chronic neuropathic pain remains unclear. In this study, we investigated the effect of optogenetic activation of ACC dopamine receptors D1- and D2expressing neurons on trigeminal neuropathic pain. Chronic constriction injury of infraorbital nerve (CCI-ION) was carried out to induce trigeminal neuropathic pain in mice. We conducted optogenetic stimulation to specifically activate D1- and D2expressing neurons in the ACC. Western blotting and immunofluorescence staining were used to examine ACC D1 and D2 expression and localization. The von Frey and real-time place preference tests were performed to measure evoked mechanical pain and nonreflexive emotional pain behaviors, respectively. We observed that dopamine receptors D1 and D2 in the ACC are primarily expressed in excitatory neurons and that the D2 receptor is differentially regulated in the early and late phases of trigeminal neuropathic pain. Optogenetic activation of D1-expressing neurons in the ACC markedly exacerbates CCI-IONinduced trigeminal neuropathic pain in both early and late phases, but optogenetic activation of D2-expressing neurons in the ACC robustly ameliorates such pain in its late phase. Our results suggest that dopamine receptors D1 and D2 in the ACC play different roles in the modulation of trigeminal neuropathic pain. Keywords Dopamine receptors . Anterior cingulate cortex . Trigeminal neuropathic pain . Optogenetic stimulation
Introduction Dopamine signaling in the brain is involved in descending pain modulation. Previous studies have shown that the regulation of dopamine receptors can be used as a therapeutic approach for trigeminal neuralgia [1–4], which is characterized by chronic neuropathic pain in facial skin innervated by * Feng Tao [email protected] 1
Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX, USA
2
Department of Physiology and Neurobiology, Zhengzhou University School of Medicine, Zhengzhou, Henan, China
3
Department of Anesthesiology, Zhengzhou University School of Medicine, Zhengzhou, Henan, China
4
Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, 3302 Gaston Ave., Dallas, TX 75246, USA
trigeminal nerve [3, 5–7]. Anterior cingulate cortex (ACC) is a critical brain center for chronic pain processing, especially for its affective component [8–10]. Dopamine receptors in the ACC contribute to a number of neuropsychiatric and neurologic
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