Tachykinin signaling in the right parabrachial nucleus mediates early-phase neuropathic pain development

Yinxia Li; Ngoc T Ha; Juan Li; Yaxin Yan; Qian Chen; Liping Cai; Weike Li; Shoupei Liu; Bo Li; Tianlin Cheng; Yangang Sun; Yingwei Wang; Juan Deng

doi:10.1016/j.neuron.2024.11.021

Tachykinin signaling in the right parabrachial nucleus mediates early-phase neuropathic pain development

Neuron. 2024 Dec 20:S0896-6273(24)00878-X. doi: 10.1016/j.neuron.2024.11.021. Online ahead of print.

Authors

Yinxia Li¹, Ngoc T Ha¹, Juan Li¹, Yaxin Yan¹, Qian Chen¹, Liping Cai¹, Weike Li¹, Shoupei Liu¹, Bo Li², Tianlin Cheng³, Yangang Sun⁴, Yingwei Wang⁵, Juan Deng⁶

Affiliations

¹ Department of Anesthesiology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.
² Department of Anesthesiology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200032, China.
³ Department of Anesthesiology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China; Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai 200032, China.
⁴ Institute of Neuroscience, Key Laboratory of Brain Cognition and Brain-Inspired Intelligence Technology, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
⁵ Department of Anesthesiology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China. Electronic address: [email protected].
⁶ Department of Anesthesiology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China. Electronic address: [email protected].

PMID: 39719702
DOI: 10.1016/j.neuron.2024.11.021

Abstract

The lateral parabrachial nucleus (PBN) is critically involved in neuropathic pain modulation. However, the cellular and molecular mechanisms underlying this process remain largely unknown. Here, we report that in mice, the right-sided, but not the left-sided, PBN plays an essential role in the development of hyperalgesia following nerve injury, irrespective of the injury side. Spino-parabrachial pathways targeting the right-sided PBN display short-term facilitation, and right-sided PBN neurons exhibit an increase in the excitability and activity after nerve injury. Inhibiting Tacr1-positive neurons, blocking Tacr1-encoding tachykinin 1 receptor (NK1R), or knocking down the Tacr1 gene in the right-sided, rather than left-sided, PBN alleviates neuropathic pain-induced sensory hypersensitivity. Additionally, the right-sided PBN plays a critical role in the development of hyperalgesia during the early phase of neuropathic pain. These results highlight the essential role of NK1R in the lateralized modulation of neuropathic pain by the PBN, providing new insights into the mechanisms underlying neuropathic pain.

Keywords: NK1R; PBN; early phase; hyperalgesia; lateralization; neuropathic pain; parabrachial nucleus; tachykinin.