Identification of brain-to-spinal circuits controlling the laterality and duration of mechanical allodynia in mice

Jiantao Huo; Feng Du; Kaifang Duan; Guangjuan Yin; Xi Liu; Quan Ma; Dong Dong; Mengge Sun; Mei Hao; Dongmei Su; Tianwen Huang; Jin Ke; Shishi Lai; Zhi Zhang; Chao Guo; Yuanjie Sun; Longzhen Cheng

doi:10.1016/j.celrep.2023.112300

Identification of brain-to-spinal circuits controlling the laterality and duration of mechanical allodynia in mice

Cell Rep. 2023 Apr 25;42(4):112300. doi: 10.1016/j.celrep.2023.112300. Epub 2023 Mar 22.

Authors

Jiantao Huo¹, Feng Du¹, Kaifang Duan¹, Guangjuan Yin¹, Xi Liu¹, Quan Ma¹, Dong Dong¹, Mengge Sun¹, Mei Hao¹, Dongmei Su¹, Tianwen Huang², Jin Ke², Shishi Lai², Zhi Zhang³, Chao Guo¹, Yuanjie Sun¹, Longzhen Cheng⁴

Affiliations

¹ Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
² Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen 518055, China.
³ Division of Life Sciences and Medicine, CAS Key Laboratory of Brain Function and Diseases, University of Science and Technology of China, Hefei 230027, China.
⁴ Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China; Department of Biology, Brain Research Center, Southern University of Science and Technology, Shenzhen 518055, China; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen 518055, China. Electronic address: chenglz@sustech.edu.cn.

PMID: 36952340
DOI: 10.1016/j.celrep.2023.112300

Abstract

Mechanical allodynia (MA) represents one prevalent symptom of chronic pain. Previously we and others have identified spinal and brain circuits that transmit or modulate the initial establishment of MA. However, brain-derived descending pathways that control the laterality and duration of MA are still poorly understood. Here we report that the contralateral brain-to-spinal circuits, from Oprm1 neurons in the lateral parabrachial nucleus (lPBN^Oprm1), via Pdyn neurons in the dorsal medial regions of hypothalamus (dmH^Pdyn), to the spinal dorsal horn (SDH), act to prevent nerve injury from inducing contralateral MA and reduce the duration of bilateral MA induced by capsaicin. Ablating/silencing dmH-projecting lPBN^Oprm1 neurons or SDH-projecting dmH^Pdyn neurons, deleting Dyn peptide from dmH, or blocking spinal κ-opioid receptors all led to long-lasting bilateral MA. Conversely, activation of dmH^Pdyn neurons or their axonal terminals in SDH can suppress sustained bilateral MA induced by lPBN lesion.

Keywords: CP: Neuroscience; Pdyn; duration; hypothalamus; laterality; mechanical allodynia; oprm1; pain; parabrachial nucleus; spinal dorsal horn; κ-opioid receptor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Central Nervous System / metabolism
Hyperalgesia* / metabolism
Hypothalamus / metabolism
Mice
Neurons / metabolism
Spinal Cord Dorsal Horn / metabolism
Spinal Cord* / metabolism