The anterior cingulate cortex projection to the dorsomedial striatum modulates hyperalgesia in a chronic constriction injury mouse model
Xiuxiu Zhuang 1,   Luping Huang 1,   Yixiao Gu 1,   Lu Wang 1,   Rong Zhang 2,   Minyuan Zhang 1,   Fei Li 3,   Yiyi Shi 1,   Yunchang Mo 1,   Qinxue Dai 1,   Chaoyi Wei 1,   Junlu Wang 1, 4
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Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, China
Department of Anesthesiology, The First Affiliated Hospital, Zhejiang University, Hangzhou City, Zhejiang Province, China
School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou City, Zhejiang Province, China
Wencheng Country People’s Hospital, Wenzhou, Zhejiang, China
Submission date: 2018-12-10
Final revision date: 2019-03-13
Acceptance date: 2019-03-26
Online publication date: 2019-05-15
Arch Med Sci 2021;17(5)
The aim of the study was to study the role of the anterior cingulate cortex (ACC)-dorsal midbrain striatum (DMS) in neuropathic pain in mice.

Material and methods:
Optogenetics has been increasingly used in neuroscience research to selectively and precisely control the activity of a defined group of central neurons to determine their roles in behavioral functions in animals. The most important opsins are blue-sensitive ChR2 and yellow-sensitive NpHR. Calcium-calmodulin dependent protein kinase Iiα (CaMKIIα) is mostly expressed in the pyramidal excitatory neurons. Mice were injected with AAV2/9-CamKII-ChR2-mCherry, AAV2/9-CamKII-eNpHR3.0-GFP or AAV2/9-CamKII-mCherry virus in the ACC region, and the optical fiber implantation was performed in the ACC or DMS region. Mice were then followed up for 2 to 8 weeks and behavioral tests were carried out in the presence or absence of the blue/yellow light (473 nm/589 nm). Pain behavioral tests with or without the blue/yellow light at the same time were performed on the third and the seventh day after the chronic constriction injury of sciatic nerve model (CCI) was established. The pain thresholds of left and right hind limbs of mice in all groups were measured.

No matter whether activating the neurons in ACC or DMS, compared with normal mice in the ChR2-off-right group, and the mCherry-on-right group, the thermal pain threshold and mechanical pain threshold of the normal mice in the ChR2-on-right group were significantly lower. When inhibiting the neurons in the ACC or DMS, on day 3 and day 7 after CCI operation, the thermal pain threshold and mechanical pain threshold of the CCI mice of the NpHR-on-right group were significantly higher compared with the NpHR-off-right and mCherry-on-right groups.

The anterior cingulate cortex-dorsal midbrain striatum may be involved in the regulation of neuropathic pain in mice.