2. Academic Validation
  3. Contribution of activating lateral hypothalamus-lateral habenula circuit to nerve trauma-induced neuropathic pain in mice

Contribution of activating lateral hypothalamus-lateral habenula circuit to nerve trauma-induced neuropathic pain in mice

  • Neurobiol Dis. 2023 May 12;106155. doi: 10.1016/j.nbd.2023.106155.
Han-Wen Gu 1,  Guang-Fen Zhang 2,  Pan-Miao Liu 1,  Wei-Tong Pan 1,  Yuan-Xiang Tao 3,  Zhi-Qiang Zhou 4,  Jian-Jun Yang 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Neuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou, China.
  • 2 Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • 3 Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, United States.
  • 4 Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China. Electronic address: zq_zhou@sina.com.
  • 5 Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Neuroscience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou, China. Electronic address: yjyangjj@126.com.
PMID: 37182721 DOI: 10.1016/j.nbd.2023.106155
Abstract

Neuropathic pain, a severe clinical symptom, significantly affects the quality of life in the patients. The molecular mechanisms underlying neuropathic pain have been the focus of research in recent decades; however, the neuronal circuit-mediated mechanisms associated with this disorder remain poorly understood. Here, we report that a projection from the lateral hypothalamus (LH) glutamatergic neurons to the lateral habenula (LHb), an excitatory LH-LHb neuronal circuit, participates in nerve injury-induced nociceptive hypersensitivity. LH glutamatergic neurons are activated and display enhanced responses to normally non-noxious stimuli following chronic constriction injury. Chemogenetic inhibition of LH glutamatergic neurons or excitatory LH-LHb circuit blocked CCI-induced nociceptive hypersensitivity. Activation of the LH-LHb circuit led to augmented responses to mechanical and thermal stimuli in mice without nerve injury. These findings suggest that LH neurons and their triggered LH-LHb circuit participate in central mechanisms underlying neuropathic pain and may be the targets for the treatment of this disorder.

Keywords

Glutamatergic neuron; Lateral habenula; Lateral hypothalamus; Neural circuit; Neuropathic pain.

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