2. Academic Validation
  3. Disinhibition of PVN-projecting GABAergic neurons in AV region in BNST participates in visceral hypersensitivity in rats

Disinhibition of PVN-projecting GABAergic neurons in AV region in BNST participates in visceral hypersensitivity in rats

  • Psychoneuroendocrinology. 2020 Jul;117:104690. doi: 10.1016/j.psyneuen.2020.104690.
Yu Song 1,  Qing-Xiang Meng 2,  Ke Wu 2,  Rong Hua 3,  Zhi-Jing Song 2,  Ying Song 2,  Xia Qin 2,  Jun-Li Cao 4,  Yong-Mei Zhang 5
Affiliations

Affiliations

  • 1 Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu Province 221004, China; Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu Province 221004, China.
  • 2 Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu Province 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu Province 221004, China.
  • 3 Department of Emergency, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China.
  • 4 Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu Province 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu Province 221004, China. Electronic address: caojl0310@aliyun.com.
  • 5 Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu Province 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu Province 221004, China. Electronic address: zhangym700@163.com.
PMID: 32417623 DOI: 10.1016/j.psyneuen.2020.104690
Abstract

Ample evidence suggests that early life stress (ELS) is a high-risk factor for the development of visceral pain disorders, whereas the mechanism underlying neuronal circuit remains elusive. Herein, we employed neonatal colorectal distension (CRD) to induce visceral hypersensitivity in rats. A combination of electrophysiology, pharmacology, behavioral test, Molecular Biology, chemogenetics and optogenetics confirmed that CRD in neonatal rats could predispose the elevated firing frequency of the parvocellular corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of hypothalamus (PVN) in adulthood, with the CRH neurons activated and the frequency of spontaneous inhibitory postsynaptic currents (sIPSC) diminished, both contributing to chronic visceral hypersensitivity. Moreover, following administration of exogenous GABA (300 mM/0.5 μL) and GABAA receptor agonist muscimol (3 mM/0.5 μL) in PVN, visceral hyperalgesia was abrogated. In addition, the PVN-projecting GABAergic neurons were mainly distributed in the anterior ventral (AV) region in the bed nucleus of stria terminalis (BNST), and the excitability of these GABAergic neurons was weakened in visceral hypersensitivity. Specific depletion of the GABAergic neurons in AV region precipitated visceral hyperalgesia. Moreover, chemogenetic activation of the PVN-projecting neurons alleviated the visceral hypersensitivity. Photoactivation of PVN-projecting GABAergic neurons abated the visceral hypersensitivity in neonatal-CRD rats, whereas photoinhibition evoked visceral hyperalgesia in naïve rats. Our findings demonstrated that disinhibition of the PVN-projecting GABAergic neurons in AV region contributed to the excitation of CRH neurons, thereby mediating visceral hypersensitivity. Our study might provide a novel insight into the neuronal circuits involved in the ELS-induced visceral hypersensitivity.

Keywords

AV region; BNST; CRH neuron; GABAergic neuron; PVN; Visceral hypersensitivity.

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