Skip to main content

Advertisement

Log in

Initiation of Acupoint Molecular Mechanisms for Manual Acupuncture Analgesia—Nuclear Factor κB Signaling Pathway

  • Acupuncture Research
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To identify the prominent molecular signaling in acupoints and explore their roles in initiating the analgesia effect of manual acupuncture (MA).

Method

A three-step study was conducted, the experiment 1 was a genome-wide analysis of the tissue at acupoint Zusanli (ST 36), including 12 Wistar rats which were divided into control, control+MA1, and control+MA7 groups. In the experiment 2, the paw withdrawal latency (PWL), immunohistochemistry and Western blot analysis of phospho-nuclear factor kappa B (NFκB) p65 (p-p65), phospho-NFκB p50 (p-p50) at ST 36 were performed on rats of saline, saline+MA, and complete Freund’s adjuvant (CFA)+MA groups (n=6). In experiment 3, 24 rats were divided into saline+DMSO, CFA+DMSO, CFA+DMSO+MA, and CFA+BAY 11–7082+MA groups, the PWL and immunofluorescence assay of NFκB p65 at ST 36 was conducted.

Result

(1) The gene: inhibitor of NFκB (Nfkbia), interleukin-1β (Il1b), interleukin-6 (Il6), chemokine c-x-c motif ligand 1 (Cxcl1), monocyte chemoattractant protein-1 (MCP-1/Ccl2) expressions in the control+MA7 group were significantly increased (P<0.05 or P<0.01), and the expression of NFκB p65 (Rela), NFκB p50 (Nfkb1) were increased in the control+MA7 group (P<0.05). (2) CFA+MA groups showed increased PWL from day 1 to 7 (P<0.01 vs. CFA), and the Western blot results were consistent with immunohistochemistry, the expression of NFκB p-p65 and NFκB p-p50 were significantly increased in the MA-related groups compared with control and CFA groups (P<0.05). (3) Compared with the CFA+DMSO+MA group, the PWL of the CFA+ BAY 11–7082+MA group decreased significantly and continued until day 5 and 7 (P<0.05 and P<0.01, respectively), and the NFκB p65 expression of CFA+BAY 11–7082+MA was significantly reduced compared with CFA+DMSO+MA (P<0.01).

Conclusion

Local NFκB signaling cascade in acupoint caused by MA is an important step in initiating the analgesic effect, which would provide new evidence for the initiation of MA-effect and improve the understanding of the scientific basis of acupuncture analgesia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ernst E. Acupuncture. Lancet Oncol 2010;11:20.

    Article  Google Scholar 

  2. Wu JN. A short history of acupuncture. J Alternat Complem Med 1996;2:19–21.

    Article  CAS  Google Scholar 

  3. Vas J, Aranda JM, Modesto M, Benítez PN, Herrera, A, Martínez B, et al. Acupuncture in patients with acute low back pain: a multicentre randomised controlled clinical trial. Pain 2012;153:1883–1889.

    Article  Google Scholar 

  4. Zachary SS, Danesh H. Acupuncture in the management of chronic pain. Topics Pain Manag 2017;32:1–9.

    Article  Google Scholar 

  5. Chessman AW. Review: acupuncture reduces migraine frequency more than usual care, sham acupuncture, or prophylactic drugs. Ann Intern Med 2016;65:C44.

    Article  Google Scholar 

  6. Greenlee H, Crew KD, Capodice J, Awad D, Jeffres A, Unger JM, et al. Methods to standardize a multicenter acupuncture trial protocol to reduce aromatase inhibitor-related joint symptoms in breast cancer patients. J Acupunct Meridian Stud 2015;8:152–158.

    Article  Google Scholar 

  7. Marchant J. Acupuncture in cancer study reignites debate about controversial technique. Nature 2017;552:157–158.

    Article  CAS  Google Scholar 

  8. Miller KR, Patel JN, Symanowski JT, Edelen CA, Walsh D. Acupuncture for cancer pain and symptom management in a palliative medicine clinic. Am J Hosp Palliat Care 2019;36:326–332.

    Article  Google Scholar 

  9. World Health Organization. Acupuncture: review and analysis reports on controlled clinical trials. Geneva 2002;1–81.

  10. World Health Organization. WHO traditional medicine strategy: 2014–2023. Geneva; 2013:1–76.

  11. Cressey D. Acupuncture for mice. Nature 2010;465:538.

    Article  CAS  Google Scholar 

  12. Fan GQ, Qian LL, Zhao Y, Fu ZH. Acupuncture analgesia:variousness and analysis. Chin Acupunct Moxibust (Chin) 2013;33:92–96.

    Google Scholar 

  13. Zhang K, Ding SS, Gong YN, Zhao X, Kai Li. Initiation mechanisms of acupuncture effect: a literature review of basic studies. J Acupunct Tuina Sci (Chin) 2020;18:75–82.

    Article  Google Scholar 

  14. Huang M, Wang XZ, Xing BB, Yang HW, Sa ZY, Zhang D, et al. Critical roles of TRPV2 channels, histamine H1 and adenosine A1 receptors in the initiation of acupoint signals for acupuncture analgesia. Sci Rep 2018;8:6523.

    Article  Google Scholar 

  15. Park JY, Park JJ, Jeon S, Doo AR, Kim SN, Lee HS, et al. From peripheral to central: the role of ERK signaling pathway in acupuncture analgesia. J Pain 2014;15:535–549.

    Article  CAS  Google Scholar 

  16. Qi J, Chen C, Meng QX, Wu Y, Wu H, Zhao TB. Crosstalk between activated microglia and neurons in the spinal dorsal horn contributes to stress-induced hyperalgesia. Sci Rep 2016;6:39442.

    Article  CAS  Google Scholar 

  17. Chen CY, Lin CN, Chern RS, Tsai YC, Chang YH, Chien CH. Neuronal activity stimulated by liquid substrates injection at Zusanli (ST36) acupoint: the possible mechanism of aquapuncture. Evid Based Complement Alternat Med 2014;2014:627342.

    PubMed  PubMed Central  Google Scholar 

  18. Goldman N, Chen M, Fujita T, Xu Q, Peng W, Liu W, et al. Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nature Neurosci 2010;53:38–39.

    Google Scholar 

  19. Cui X, Liu K, Xu D, Zhang Y, He X, Liu H, et al. Mast cell deficiency attenuates acupuncture analgesia for mechanical pain using c-kit gene mutant rats. J Pain Res 2018;11:483–495.

    Article  CAS  Google Scholar 

  20. Zhou W, Lei RX, Zuo CY, Yue YQ, Luo Q, Zhang CS, et al. Analgesic effect of moxibustion with different temperature on inflammatory and neuropathic pain mice: a comparative study. Evid Based Complement Alternat Med 2017;2017:4373182.

    PubMed  PubMed Central  Google Scholar 

  21. Xu Y, Hong SH, Zhao X, Wang SJ, Xu ZF, Ding SS, et al. Acupuncture alleviates rheumatoid arthritis by immune-network modulation. Am J Chin Med 2018;46:997–1019.

    Article  CAS  Google Scholar 

  22. Zhu D, Fan T, Huo X, Cui J, Cheung CW, Xia Z. Progressive increase of inflammatory CXCR4 and TNF-alpha in the dorsal root ganglia and spinal cord maintains peripheral and central sensitization to diabetic neuropathic pain in rats. Mediators Inflamm 2019;2019:4856156.

    PubMed  PubMed Central  Google Scholar 

  23. Zhang K, Guo XM, Yan YW, Liu YY, Xu ZF, Zhao X, et al. Applying statistical and complex network methods to explore the key signaling molecules of acupuncture regulating neuroendocrine-immune network. Evid Based Complement Alternat Med 2018;2018:9260630.

    PubMed  PubMed Central  Google Scholar 

  24. Oeckinghaus A, Hayden MS, Ghosh S. Crosstalk in NF-κ B signaling pathways. Nat Immunol 2011;12:695–708.

    Article  CAS  Google Scholar 

  25. Olga K, Volodymyr K, Angela S, Andrij S, Viacheslav VK, Victor D, et al. Spinal PKCα inhibition and gene-silencing for pain relief: AMPAR trafficking at the synapses between primary afferents and sensory interneurons. Sci Rep 2018;8:10285.

    Article  Google Scholar 

  26. Pinho-Ribeiro FA, Verri WA Jr, Chiu IM. Nociceptor sensory neuron-immune interactions in pain and inflammation. Trends Immunol 2017;38:5–19.

    Article  CAS  Google Scholar 

  27. Li NC, Li MY, Chen B, Guo Y. A new perspective of acupuncture: the interaction among three networks leads to neutralization. Evid Based Complement Alternat Med 2019;2019:2326867.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Zhang K, Yang T, Zhang YF and Yan YW carried out the experiments, Zhang K, Yang T and Zhang YF contributed to statistical analysis, Zhang K, Zhao X, Xu ZF, Gong YN, Liu YY wrote the manuscript, Guo Y, Guo YM and Zhao X designed the project and supervised the work and provided the facilities for the study. All authors read the manuscript and approved the final version.

Corresponding author

Correspondence to Xue Zhao.

Additional information

Conflict of Interest

The authors declare that they have no competing interest.

Supported by the China Postdoctoral Science Foundation (No. 2019M651044), and the National Natural Science Foundation of China (No. 81330088)

Supplementary material to

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, K., Zhao, X., Yang, T. et al. Initiation of Acupoint Molecular Mechanisms for Manual Acupuncture Analgesia—Nuclear Factor κB Signaling Pathway. Chin. J. Integr. Med. 27, 933–939 (2021). https://doi.org/10.1007/s11655-020-3435-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-020-3435-6

Keywords

Navigation