Map activation of various brain regions using different frequencies of electroacupuncture ST36, utilizing the FosCreER strategy

Abstract

Objective: Electroacupuncture (EA) is an alternative treatment option for pain. Different frequencies of EA have different pain-relieving effects; however, the central mechanism is still not well understood.
Methods: The Fos2A-iCreER (TRAP):Ai9 mice were divided into three groups (sham, 2 Hz, and 100 Hz). The mice were intraperitoneally injected with 4-hydroxytamoxifen (4-OHT) immediately after EA at Zusanli (ST36) for 30 min to record the activated neurons. One week later, the mice were sacrificed, and the number of TRAP-treated neurons activated by EA in the thalamus, amygdala, cortex, and hypothalamus was determined.
Results: In the cortex, 2 Hz EA activated more TRAP-treated neurons than 100 Hz EA did in the cingulate cortex area 1 (Cg1) and primary somatosensory cortex (S1), and 2 and 100 Hz EAs did not differ from sham EA. TRAP-treated neurons activated by 2 Hz EA were upregulated in the insular cortex (IC) and secondary somatosensory cortex (S2) compared with those activated by 100 Hz and sham EA. In the thalamus, the number of TRAP-treated neurons activated by 2 Hz EA was elevated in the paraventricular thalamic nucleus (PV) compared with those activated by sham EA. In the ventrolateral thalamic nucleus (VL), the number of TRAP-treated neurons activated by 2 Hz EA was significantly upregulated compared with those activated by 100 Hz EA, and sham EA showed no difference compared with 2 or 100 Hz EA. TRAP-treated neurons were more frequently activated in the ventral posterolateral thalamic nucleus (VPL) by 2 Hz EA than by 100 Hz or sham EA.
Conclusions: Low-frequency EA ST36 effectively activates neurons in the Cg1, S1, S2, IC, VPL, PV, and VL. The enhanced excitability of the aforementioned nuclei induced by low-frequency EA may be related to its superior efficacy in the treatment of neuropathological pain.

Keywords

Amygdala / Cortex / EA-TRAPed neurons / Electroacupuncture / Frequency / Hypothalamus / Thalamus

Conflict of interest statement

The authors declare no conflict of interest.

Funding

This work was supported by the National Natural Science Fund of China (82374561, 82174490, 81873360), the Zhejiang Medical and Health Science and Technology Program (2021RC098), the Research Project of Zhejiang Chinese Medical University (2022JKZKTS44).

Author contributions

Jianqiao Fang, Junfang Fang, and Junying Du designed the study. Zi Guo, Tiancheng Sun, and Naixuan Wei performed the experiment and wrote the article. Ru Ye, Xiaochang Ge, and Lu Guan participated in analyzing the results. Xiaomei Shao and Shuang Qiu reviewed the text after conducting data analysis. The final manuscript was read and approved by all writers.

Ethical approval of studies and informed consent

All mice experimental were approved by the Animal Care of Zhejiang Chinese Medical Animal Care and Welfare Committee of Zhejiang China (IACUC-20200302-06).

Acknowledgments

We appreciate the technical support from the Public Platform of Medical Research Center, Academy of Chinese Medical Science, Zhejiang Chinese Medical University.

Data availability

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

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Acupuncture and Herbal Medicine