Advanced Search

Journal of Traditional Chinese Medicine >

2025 , Vol. 45 >Issue 5: 1019 - 1027

DOI: https://doi.org/10.19852/j.cnki.jtcm.2025.05.008

Original Articles

Characterization of acupuncture on central amino acid metabolism based on targeted neurotransmitter analysis in mice with inflammatory pain

  • Yue WANG ,
  • Xingxing LIU ,
  • Yi GUO ,
  • Yongming GUO ,
  • Gongming YUAN ,
  • Yu ZHANG ,
  • Zhiyu ZHENG ,
  • Yuan XU ,
  • Yuan LI
Expand
  • 1 School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
    2 National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300380, China
    3 College of Acupuncture and Massage Health and Rehabilitation College, Nanjing University of Chinese Medicine, Nanjing 210023, China

Received date: 2024-06-11

  Accepted date: 2024-11-19

  Online published: 2025-09-15

Supported by

National Natural Science Foundation of China: Study on Acupuncture Alleviate Rheumatoid Arthritis Effect and Mechanism via miR-155 Reduce Monocyte Chemokine and Chemokine Receptor Expression(82004473);Natural Science Foundation of Jiangsu Province: Study on the Role and Mechanism of Aryl Hydrocarbon Receptor-mediated Acupuncture in Regulating Immune Homeostasis of the Gut-joint Axis in Rheumatoid Arthritis(BK20230453)

Fold

Abstract

OBJECTIVE: To investigate the effect of central amino acid metabolic profiles on acupuncture analgesia.

METHODS: BALB/c mice were injected with Complete Freund's Adjuvant (CFA) and acupuncture was applied at Zusanli (ST36) for 7 d after modeling. Paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT) were tested during the experiment. The level of prostaglandin E2 (PGE2) was measured by enzyme-linked immunosorbent assay (ELISA). Using liquid chromatography-mass spectrometry (LC-MS/MS) based on the multiple reaction monitoring (MRM)-targeted metabolomic approach, neurotransmitter in the brain and spinal cord as well as were detected, further tryptophan metabolites in spinal cord were detected, and the data was analyzed using multiquant software.

RESULTS: Acupuncture significantly improved the PWTL and PWMT on the modeling side of CFA mice, and simultaneously, decreased the PGE2 level. Based on targeted neurotransmitter analysis, acupuncture increased the expression of phenylethylamine and decreased N-acetyl serotonin in the brain, while significantly up-regulated serotonin, and down-regulated the levels of homovanillic acid, 5-hydroxy-L-tryptophan and 3,4-Dihydroxyphenylethylene Glyco in the spinal cord. Further investigation targeted tryptophan metabolism found that acupuncture considerably decreased the content of tryptophan and L-kynurenine, but increased serotonin.

CONCLUSIONS: This study aims to assess changes in central neurotransmitters of CFA mice treated with acupuncture, revealing that abnormalities in central neurotransmitter metabolism may be a potential biochemical basis for pain. More importantly, our preliminary study suggests the potential role of tryptophan and its metabolites in acupuncture analgesia, which may provide new insight and direction for the pain management interface of neurometabolism.

Key words： acupuncture; pain; metabolomics; tryptophan; kynurenine

Cite this article

Yue WANG , Xingxing LIU , Yi GUO , Yongming GUO , Gongming YUAN , Yu ZHANG , Zhiyu ZHENG , Yuan XU , Yuan LI . Characterization of acupuncture on central amino acid metabolism based on targeted neurotransmitter analysis in mice with inflammatory pain[J]. Journal of Traditional Chinese Medicine, 2025 , 45(5) : 1019 -1027 . DOI: 10.19852/j.cnki.jtcm.2025.05.008

References

1. Cohen SP, Vase L, Hooten WM. Chronic pain: an update on burden, best practices, and new advances. Lancet 2021; 397: 2082-97.
2. Qiao L, Guo M, Qian J, et al. Research advances on acupuncture analgesia. Am J Chin Med 2020; 48: 245-58.
3. Gunn J, Hill MM, Cotten BM, et al. An analysis of biomarkers in patients with chronic pain. Pain Physician 2020; 23: E41-9.
4. Zhang Q, Zhou M, Huo M, et al. Mechanisms of acupuncture-electroacupuncture on inflammatory pain. Mol Pain 2023; 19: 1-22.
5. Gong Y, Li N, Lyu Z, et al. The neuro-immune microenvironment of acupoints-initiation of acupuncture effectiveness. J Leukoc Biol 2020; 108: 189-98.
6. Cseh EK, Veres G, K?rtési T et al. Neurotransmitter and tryptophan metabolite concentration changes in the complete Freund's adjuvant model of orofacial pain. J Headache Pain 2020; 21: 35.
7. Ciapa?a K, Mika J, Rojewska E. The kynurenine pathway as a potential target for neuropathic pain therapy design: from basic research toclinical perspectives. Int J Mol Sci 2021; 22: 11055.
8. Jovanovic F, Candido KD, Knezevic NN. The role of the kynurenine signaling pathway in different chronic pain conditions and potential use of therapeutic agents. Int J Mol Sci 2020; 21: 6045.
9. Lyu Z, Guo Y, Gong Y, et al. The role of neuroglial crosstalk and synaptic plasticity-mediated central sensitization in acupuncture analgesia. Neural Plast 2021; 2021: 8881557.
10. American Veterinary Medical Association. AVMA guidelines for the euthanasia of animals:2020 edition. American Veterinary Medical Association online, 2020-02-24, cited 2021-01-01; 60-4. Avilable from URL: https://www.avma.org/resources-tools/avma-policies/avma-guidelines-euthanasia-animals .
11. Xu Y, Hong S, Zhao X, et al. Acupuncture alleviates rheumatoid arthritis by immune-network modulation. Am J Chin Med 2018; 46: 997-1019.
12. Kanda H, Kobayashi K, Yamanaka H, et al. Localization of prostaglandin E 2 synthases and E-prostanoid receptors in the spinal cord in a rat model of neuropathic pain. Brain Res 2021; 1750: 147153.
13. Tanaka M, T?r?k N, Tóth F, et al. Co-players in chronic pain: neuroinflammation and the tryptophan-kynurenine metabolic pathway. Biomedicines 2021; 9: 897.
14. K?rtési T, Spekker E, Vécsei L. Exploring the tryptophan metabolic pathways in migraine-related mechanisms. Cells 2022; 11: 3795.
15. Pinho-Ribeiro FA, Verri WA Jr, Chiu IM. Nociceptor sensory neuron-immune interactions in pain and inflammation. Trends Immunol 2017; 38: 5-19.
16. Zhang R, Lao L, Ren K, Berman BM. Mechanisms of acupuncture- electroacupuncture on persistent pain. Anesthesiology 2014; 120: 482-503.
17. Badawy AA. Kynurenine pathway of tryptophan metabolism: regulatory and functional aspects. Int J Tryptophan Res 2017; 10: 1178646917691938.
18. Savitz J. The kynurenine pathway: a finger in every pie. Mol Psychiatry 2020; 25: 131-47.
19. Pires AS, Sundaram G, Heng B, et al. Recent advances in clinical trials targeting the kynurenine pathway. Pharmacol Ther 2022; 236: 108055.
20. Kim H, Chen L, Lim G, et al. Brain indoleamine 2,3-dioxygenase contributes to the comorbidity of pain and depression. J Clin Invest 2012; 122: 2940-54.
21. Lukács M, Warfvinge K, Kruse LS, et al. KYNA analogue SZR72 modifies CFA-induced dural inflammation-regarding expression of pERK1/2 and IL-1β in the rat trigeminal ganglion J Headache Pain 2016; 17: 64.
22. Lukács M, Warfvinge K, Tajti J, et al. Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis: attenuated by KYNA derivate (SZR72). J Headache Pain 2017; 18: 39.
23. Maganin AG, Souza GR, Fonseca MD, et al. Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice. J Clin Invest 2022; 132: e153805.
24. Rojewska E, Ciapa?a K, Piotrowska A, et al. Pharmacological inhibition of indoleamine 2,3-dioxygenase-2 and kynurenine 3-monooxygenase, enzymes of the kynurenine pathway, significantly diminishes neuropathic pain in a rat model. Front Pharmacol 2018; 9: 724.
25. Rojewska E, Piotrowska A, Makuch W, et al. Pharmacological kynurenine 3-monooxygenase enzyme inhibition significantly reduces neuropathic pain in a rat model. Neuropharmacology 2016; 102: 80-91.
26. Yaksh TL, Schwarcz R, Snodgrass HR. Characterization of the effects of L-4-Chlorokynurenine on nociception in rodents. J Pain 2017; 18: 1184-96.
27. Pineda-Farias JB, Pérez-Severiano F, González-Esquivel DF, et al. The L-kynurenine-probenecid combination reduces neuropathic pain in rats. Eur J Pain 2013; 17: 1365-73.
28. Zhang Q, Li Q, Liu S, et al. Decreased amino acids in the brain might contribute to the progression of diabetic neuropathic pain. Diabetes Res Clin Pract 2021; 176: 108790.
29. Russo MA, Georgius P, Pires AS, et al. Novel immune biomarkers in complex regional pain syndrome. J Neuroimmunol 2020; 347: 577330.
30. Barjandi G, Louca Jounger S, L?fgren M, et al. Plasma tryptophan and kynurenine in females with temporomandibular disorders and fibromyalgia-An exploratory pilot study. J Oral Rehabil 2020; 47: 150-7.
31. Staats Pires A, Tan VX, Heng B, et al. Kynurenine and tetrahydrobiopterin pathways crosstalk in pain hypersensitivity. Front Neurosci 2020; 14: 620.
32. Jiang SW, Lin YW, Hsieh CL. Electroacupuncture at Hua Tuo Jia Ji acupoints reduced neuropathic pain and increased GABAA receptors in rat spinal cord. Evid Based Complement Alternat Med 2018; 2018: 8041820.
33. Huang CP, Lin YW, Lee DY, Hsieh CL. Electroacupuncture relieves CCI-induced neuropathic pain involving excitatory and inhibitory neurotransmitters. Evid Based Complement Alternat Med 2019; 2019: 6784735.
34. Zhang Y, Li A, Xin J, et al. Involvement of spinal serotonin receptors in electroacupuncture anti-hyperalgesia in an inflammatory pain rat model. Neurochem Res 2011; 36: 1785-92.
35. Cong W, Peng Y, Meng B, Jia X, Jin Z. The effect of electroacupuncture on regulating pain and depression-like behaviors induced by chronic neuropathic pain. Ann Palliat Med 2021; 10: 104-13.
36. Lee MJ, Ryu JS, Won SK, et al. Effects of acupuncture on chronic stress-induced depression-like behavior and its central neural mechanism. Front Psychol 2019; 10: 1353.
37. Han X, Wu H, Yin P, et al. Electroacupuncture restores hippocampal synaptic plasticity via modulation of 5-HT receptors in a rat model of depression. Brain Res Bull 2018; 139: 256-62.
38. Roth W, Zadeh K, Vekariya R, Ge Y, Mohamadzadeh M. Tryptophan metabolism and gut-brain homeostasis. Int J Mol Sci 2021; 22: 2973.
Options
Outlines

/

〈 〉