Corticotropin-releasing hormone neurons in the paraventricular hypothalamic nucleus modulate gastric motility via electroacupuncture

Abstract

Objectives: Acute gastric distension (GD) impairs gastric motility and engages central stress circuits. We tested whether electroacupuncture (EA) at RN12/BL21 restores motility and probed mechanisms in the paraventricular nucleus (PVN), focusing on corticotropin-releasing hormone (CRH) neurons.

Methods: Rats underwent graded gastric balloon distension (20, 40, 60 mmHg). Gastric motility and electrogastrography determined the dysmotility threshold. Animals were randomized to EA at RN12, BL21, RN12 + BL21, or sham. PVN single-unit and local field potential activity were recorded at baseline, during GD, and after EA. Cellular Fos proto-oncogene (c-Fos)/CRH double labeling quantified PVN activation. To test causality, the CRH receptor antagonist Astressin was bilaterally microinjected into the PVN, alone or combined with EA.

Results: GD at 40 mmHg markedly suppressed gastric motility amplitude without altering slow-wave frequency, establishing this pressure as a reliable acute GD model. EA at RN12 and BL21 significantly enhanced gastric motility, with combined stimulation producing synergistic effects. GD robustly increased c-Fos expression in the PVN, including within CRH neurons, and elevated PVN neuronal firing rates and power spectral density. EA attenuated GD-induced PVN hyperactivity, reducing neuronal firing rates, power spectral energy, and local field potential activity. Immunofluorescence confirmed that EA suppressed GD-induced activation of PVN CRH neurons, with combined stimulation at RN12 and BL21 producing greater inhibition than either acupoint alone. PVN microinjection of Astressin restored gastric motility and reduced CRH neuronal activation, whereas the combination of EA and Astressin produced an additive effect on gastric motor function.

Conclusions: EA at RN12 and BL21 reverses GD-induced gastric dysmotility by dampening PVN hyperexcitability, particularly within CRH-expressing neurons. Dual-acupoint stimulation confers superior efficacy, and CRH blockade augments EA. These findings identify PVN CRH neurons as key substrates mediating EA’s central control of visceral function under acute stress.

Keywords

Corticotropin-releasing hormone / Electroacupuncture / Gastric distension / Gastric motility / Hypothalamic paraventricular nucleus

Conflict of interest statement

The authors declare no conflict of interest.

Funding

This work was supported by the Young Scientists Fund of the National Natural Science Foundation of China (82405244), the National Natural Science Foundation of China (82474224), the Center for Xin’an Medicine and Modernization of Traditional Chinese Medicine at IHM (2023CXMMTCM016), and the National Training Program of Innovation for Undergraduates (20251036961).

Author contributions

Material preparation, data collection, and analysis were carried out by Xiyang Wang, Yi Yuan, Ran Zhou, Juying Wang, and Hongkun Ma. Supplementary experiments were conducted by Ran Zhou and Juying Wang. The first draft of the manuscript was written by Xiyang Wang, with the study conceptualized by Xiyang Wang and Guoming Shen. Manuscript review and editing were performed by Mengting Zhang, Ran Zhou, and Juying Wang. Hao Wang and Shun Huang supervised the project, and funding was provided by Xiyang Wang and Guoming Shen.

Ethical approval of studies and informed consent

All experiments were conducted in accordance with the ARRIVE guidelines and were approved by the Animal Experimentation Ethics Committee of Anhui University of Traditional Chinese Medicine (Reference No. AHUCM-rats-2024224).

Acknowledgments

We thank all co-authors for their valuable contributions to this study. Schematic figures were prepared using BioRender.com.

Data availability

All data generated or analyzed during this study are included in this published article.

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