Parabrachial nucleus circuit governs neuropathic pain-like behavior

Li Sun (), Rui Liu, Fang Guo, Man-qing Wen, Xiao-lin Ma, Kai-yuan Li, Hao Sun, Ceng-lin Xu, Yuan-yuan Li, Meng-yin Wu, Zheng-gang Zhu, Xin-jian Li, Yan-qin Yu, Zhong Chen, Xiang-yao Li and Shumin Duan ()
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Li Sun: Zhejiang University School of Medicine
Rui Liu: Zhejiang University School of Medicine
Fang Guo: Zhejiang University School of Medicine
Man-qing Wen: Zhejiang University School of Medicine
Xiao-lin Ma: Zhejiang University School of Medicine
Kai-yuan Li: Zhejiang University School of Medicine
Hao Sun: Zhejiang University School of Medicine
Ceng-lin Xu: Zhejiang University School of Medicine
Yuan-yuan Li: Zhejiang University School of Medicine
Meng-yin Wu: Zhejiang University
Zheng-gang Zhu: Zhejiang University School of Medicine
Xin-jian Li: Zhejiang University School of Medicine
Yan-qin Yu: Zhejiang University School of Medicine
Zhong Chen: Zhejiang University School of Medicine
Xiang-yao Li: Zhejiang University School of Medicine
Shumin Duan: Zhejiang University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-21

Abstract: Abstract The lateral parabrachial nucleus (LPBN) is known to relay noxious information to the amygdala for processing affective responses. However, it is unclear whether the LPBN actively processes neuropathic pain characterized by persistent hyperalgesia with aversive emotional responses. Here we report that neuropathic pain-like hypersensitivity induced by common peroneal nerve (CPN) ligation increases nociceptive stimulation-induced responses in glutamatergic LPBN neurons. Optogenetic activation of GABAergic LPBN neurons does not affect basal nociception, but alleviates neuropathic pain-like behavior. Optogenetic activation of glutamatergic or inhibition of GABAergic LPBN neurons induces neuropathic pain-like behavior in naïve mice. Inhibition of glutamatergic LPBN neurons alleviates both basal nociception and neuropathic pain-like hypersensitivity. Repetitive pharmacogenetic activation of glutamatergic or GABAergic LPBN neurons respectively mimics or prevents the development of CPN ligation-induced neuropathic pain-like hypersensitivity. These findings indicate that a delicate balance between excitatory and inhibitory LPBN neuronal activity governs the development and maintenance of neuropathic pain.

Date: 2020
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DOI: 10.1038/s41467-020-19767-w

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