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

• Published in: Cell reports (Cambridge) 2023-04, Vol.42 (4), p.112300-112300, Article 112300
• Main Authors: Huo, Jiantao, Du, Feng, Duan, Kaifang, Yin, Guangjuan, Liu, Xi, Ma, Quan, Dong, Dong, Sun, Mengge, Hao, Mei, Su, Dongmei, Huang, Tianwen, Ke, Jin, Lai, Shishi, Zhang, Zhi, Guo, Chao, Sun, Yuanjie, Cheng, Longzhen
• Format: Article
• Language: English
• Subjects: duration; hypothalamus; laterality; mechanical allodynia; oprm1; pain; parabrachial nucleus; Pdyn; spinal dorsal horn; κ-opioid receptor
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112300

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 (lPBNOprm1), via Pdyn neurons in the dorsal medial regions of hypothalamus (dmHPdyn), 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 lPBNOprm1 neurons or SDH-projecting dmHPdyn neurons, deleting Dyn peptide from dmH, or blocking spinal κ-opioid receptors all led to long-lasting bilateral MA. Conversely, activation of dmHPdyn neurons or their axonal terminals in SDH can suppress sustained bilateral MA induced by lPBN lesion. [Display omitted] •lPBNOprm1→dmHPdyn→SDH circuit controls the duration and laterality of MA•lPBNOprm1 and dmHPdyn neurons control the opening of bilateral gates for MA in SDH•“Hypothalamic Dyn→spinal KOR” inhibitory system negatively modulates bilateral MA In some patients, a local injury can trigger long-lasting, bilateral mechanical pain hypersensitivity. Huo et al. describe that contralateral brain-to-spinal circuits prevent nerve injury from inducing contralateral mechanical allodynia and reduce the duration of bilateral mechanical allodynia induced by capsaicin.