Therapeutic effects of Mongolian medical warm acupuncture on neuropathic pain via gut microbiota and inflammatory pathway regulation in a chronic constriction injury rat model

Authors

  • Husileng Meng Mongolian Medicine School, Inner Mongolia Medical University, No. 5 Xinhua Street, Hohhot, China https://orcid.org/0009-0003-6732-1239
  • Hong Yu Inner Mongolia Key Laboratory of Disease-Related Biomarkers, The Second Affiliated Hospital, Baotou Medical College, No. 30 Hudemulin Avenue, Baotou, China https://orcid.org/0009-0008-6813-5143
  • Suhe Gang Mongolian Medicine School, Inner Mongolia Medical University, No. 5 Xinhua Street, Hohhot, China https://orcid.org/0009-0004-9324-8669
  • Agula Bo 1. Mongolian Medicine School, Inner Mongolia Medical University, No. 5 Xinhua Street, Hohhot, China; 2. Inner Mongolia Key Laboratory of Disease-Related Biomarkers, The Second Affiliated Hospital, Baotou Medical College, No. 30 Hudemulin Avenue, Baotou, China https://orcid.org/0000-0003-2045-8919
  • Zhanli Wang Inner Mongolia Key Laboratory of Disease-Related Biomarkers, The Second Affiliated Hospital, Baotou Medical College, No. 30 Hudemulin Avenue, Baotou, China https://orcid.org/0000-0002-1980-6085

Keywords:

Mongolian medical warm acupuncture, Neuropathic pain, Chronic constriction injury, Gut microbiota, Inflammation

Abstract

Paper description:

  • Mongolian medical warm acupuncture exhibits beneficial therapeutic effects on neuropathic pain. This study may assist in elucidating its underlying mechanisms.
  • 16S rRNA gene sequencing, ELISA, and real-time PCR were used to identify the effects of Mongolian medical warm acupuncture (MMWA) on gut microbiota and inflammation in the chronic constriction injury (CCI) rat model.
  • MMWA alleviated neuropathic pain by regulating gut microbiota and inflammation.
  • Our results contribute to understanding the regulatory mechanisms underlying Mongolian medical warm acupuncture in neuropathic pain.

Abstract: The study was designed to determine whether Mongolian medical warm acupuncture (MMWA) can alleviate neuropathic pain through regulating gut microbiota and inflammation-related pathways in the chronic constriction injury (CCI) rat model. Rats were randomly divided into three groups: sham, model, and treatment. A bilateral chronic constriction injury (CCI) was induced to establish a rat model of neuropathic pain. Rats in the treatment group received MMWA at the Heyi and Shen acupoints once daily for seven consecutive days. Pain-related behaviors were evaluated using mechanical pain threshold and thermal withdrawal latency measurements. The mRNA levels of c-fos in spinal dorsal horns were determined using real-time PCR. Gut microbiota was analyzed by 16S ribosomal RNA sequencing. Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were evaluated by enzyme-linked immunosorbent assay (ELISA) analysis. MMWA could relieve behavioral symptoms (P<0.01). MMWA intervention significantly suppressed the expression of c-fos in CCI rats (P<0.05). The relative abundance of gut bacteria was disturbed in CCI rats, with the microbiota disorder ameliorated by MMWA. KEGG enrichment analysis revealed that changes in gut microbiota were associated with the pentose and glucuronate interconversion pathway and secondary bile acid biosynthesis. The concentrations of IL-1β, IL-6, and TNF-α in CCI rats were increased (P<0.05), an effect that was reversed by MMWA intervention (P<0.05). The current study indicated that the MMWA could effectively alleviate neuropathic pain by modulating gut microbiota and inhibiting inflammation in the CCI rat model, suggesting that gut microbiota could be a promising potential biological target for treating neuropathic pain.

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References

Finnerup NB, Kuner R, Jensen TS. Neuropathic pain: From mechanisms to treatment. Physiol Rev. 2021;101(1):259-301. https://doi.org/10.1152/physrev.00045.2019

van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014;155(4):654-62. https://doi.org/10.1016/j.pain.2013.11.013

Cruz-Mendoza F, Jauregui-Huerta F, Aguilar-Delgadillo A, García-Estrada J, Luquin S. Immediate early gene c-fos in the brain: focus on glial cells. Brain Sci. 2022;12(6):687. https://doi.org/10.3390/brainsci12060687

Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006;10(4):287-333. https://doi.org/10.1016/j.ejpain.2005.06.009

Cavalli E, Mammana S, Nicoletti F, Bramanti P, Mazzon E. The neuropathic pain: An overview of the current treatment and future therapeutic approaches. Int J Immunopathol Pharmacol. 2019;33:2058738419838383. https://doi.org/10.1177/2058738419838383

Han J, Lin H, Huang W. Modulating gut microbiota as an anti-diabetic mechanism of berberine. Med Sci Monit. 2011;17(7):RA164-7. https://doi.org/10.12659/MSM.881842

Morreale C, Bresesti I, Bosi A, Baj A, Giaroni C, Agosti M, Salvatore S. Microbiota and pain: Save your gut feeling. Cells. 2022;11(6):971. https://doi.org/10.3390/cells11060971

Kakoty V, K C S, Dubey SK, Yang CH, Kesharwani P, Taliyan R. The gut-brain connection in the pathogenicity of Parkinson disease: Putative role of autophagy. Neurosci Lett. 2021;753:135865. https://doi.org/10.1016/j.neulet.2021.135865

Chen P, Wang C, Ren YN, Ye ZJ, Jiang C, Wu ZB. Alterations in the gut microbiota and metabolite profiles in the context of neuropathic pain. Mol Brain. 2021;14(1):50. https://doi.org/10.1186/s13041-021-00765-y

Hua D, Li S, Li S, Wang X, Wang Y, Xie Z, Zhao Y, Zhang J, Luo A. Gut microbiome and plasma metabolome signatures in middle-aged mice with cognitive dysfunction induced by chronic neuropathic pain. Front Mol Neurosci. 2022;14:806700. https://doi.org/10.3389/fnmol.2021.806700

Ding W, You Z, Chen Q, Yang L, Doheny J, Zhou X, Li N, Wang S, Hu K, Chen L, Xia S, Wu X, Wang C, Zhang C, Chen L, Ritchie C, Huang P, Mao J, Shen S. Gut microbiota influences neuropathic pain through modulating proinflammatory and anti-inflammatory T cells. Anesth Analg. 2021;132(4):1146-55. https://doi.org/10.1213/ANE.0000000000005155

Pane K, Boccella S, Guida F, Franzese M, Maione S, Salvatore M. Role of gut microbiota in neuropathy and neuropathic pain states: A systematic preclinical review. Neurobiol Dis. 2022;170:105773. https://doi.org/10.1016/j.nbd.2022.105773

Jing Y, Yu Y, Bai F, Wang L, Yang D, Zhang C, Qin C, Yang M, Zhang D, Zhu Y, Li J, Chen Z. Effect of fecal microbiota transplantation on neurological restoration in a spinal cord injury mouse model: involvement of brain-gut axis. Microbiome. 2021;9(1):59. https://doi.org/10.1186/s40168-021-01007-y

Yu JW, Yuan HW, Bao LD, Si LG. Interaction between piperine and genes associated with sciatica and its mechanism based on molecular docking technology and network pharmacology. Mol Divers. 2021;25(1):233-48. https://doi.org/10.1007/s11030-020-10055-9

A R, Bao Q, Sai YC, Te M, Hu R, Sa R, Mu R, Bo A. Clinical observation of warming acupuncture and moxibustion at the temples combined with Deanxit in the treatment of tension headache with anxiety and depression: a retrospective study. Ann Palliat Med. 2021;10(5):5541-8. https://doi.org/10.21037/apm-21-925

A G, Li X, Su B, Lian H, Bao M, Liang Y, Chen Y, Jia Y, Bao L, Su X. Effect of Mongolian warm acupuncture on the gene expression profile of rats with insomnia. Acupunct Med. 2019;37(5):301-11. https://doi.org/10.1136/acupmed-2016-011243

Shui L, Yi RN, Wu YJ, Bai SM, Si Q, Bo AG, Wuyun GR, Si LG, Chen YS, Lu J. Effects of Mongolian warm acupuncture on iNOS/NO and inflammatory cytokines in the hippocampus of chronic fatigue rats. Front Integr Neurosci. 2020;13:78. https://doi.org/10.3389/fnint.2019.00078

Yu H, Yu H, Si L, Meng H, Chen W, Wang Z, Gula A. Influence of warm acupuncture on gut microbiota and metabolites in rats with insomnia induced by PCPA. PLoS One. 2022;17(4):e0267843. https://doi.org/10.1371/journal.pone.0267843

Rowin J. Integrative neuromuscular medicine: Neuropathy and neuropathic pain: Consider the alternatives. Muscle Nerve. 2019;60(2):124-36. https://doi.org/10.1002/mus.26510

Wang C, Wu L, Zhou R, Song C, Chen P, Huang S, Ali Khan A, Lu D, Hu Y, Chen L. Integration of microbiota and metabolomics reveals the analgesic mechanisms of emodin against neuropathic pain. Int Immunopharmacol. 202;125(Pt A):111170. https://doi.org/10.1016/j.intimp.2023.111170

Saiyin CK, Ai LY, Song ML, Luo T, Zhao J, Aru N, Deng TT. Mongolian medicine three acupoints balance needling improves depressive behavior by regulating p11/tPA/BDNF pathway and miRNA-16 of hippocampus and middle raphe nucleus in depression model rats. Zhen Ci Yan Jiu. 2021;46(9):742-50.

Zhang X, Wang J, Sui A, Zhang N, Lv Q, Liu Z. Antinociceptive effect of magnolol in a neuropathic pain model of mouse. J Pain Res. 2021;14:2083-93. https://doi.org/10.2147/JPR.S317204

Yu X, Zhang F, Chen B. Effect of transcutaneous electrical acupuncture point stimulation at different frequencies in a rat model of neuropathic pain. Acupunct Med. 2017;35(2):142-7. https://doi.org/10.1136/acupmed-2016-011063

Zhao X, Xu Y, Zhao Q, Chen CR, Liu AM, Huang ZL. Curcumin exerts antinociceptive effects in a mouse model of neuropathic pain: descending monoamine system and opioid receptors are differentially involved. Neuropharmacology. 2012;62(2):843-54. https://doi.org/10.1016/j.neuropharm.2011.08.050

Lin B, Wang Y, Zhang P, Yuan Y, Zhang Y, Chen G. Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy. J Headache Pain. 2020;21(1):103. https://doi.org/10.1186/s10194-020-01170-x

Ellis RJ, Heaton RK, Gianella S, Rahman G, Knight R. Reduced gut microbiome diversity in people with HIV who have distal neuropathic pain. J Pain. 2022;23(2):318-25. https://doi.org/10.1016/j.jpain.2021.08.006

Li R, Wang F, Dang S, Yao M, Zhang W, Wang J. Integrated 16S rRNA gene sequencing and metabolomics analysis to investigate the important role of osthole on gut microbiota and serum metabolites in neuropathic pain mice. Front Physiol. 2022;13:813626. https://doi.org/10.3389/fphys.2022.813626

Lian N, Shen M, Zhang K, Pan J, Jiang Y, Yu Y, Yu Y. Drinking hydrogen-rich water alleviates chemotherapy-induced neuropathic pain through the regulation of gut microbiota. J Pain Res. 2021;14:681-91. https://doi.org/10.2147/JPR.S288289

Lin H, Meng L, Sun Z, Sun S, Huang X, Lin N, Zhang J, Lu W, Yang Q, Chi J, Guo H. Yellow wine polyphenolic compound protects against doxorubicin- induced cardiotoxicity by modulating the composition and metabolic function of the gut microbiota. Circ Heart Fail. 2021;14(10):e008220. https://doi.org/10.1161/CIRCHEARTFAILURE.120.008220

Zheng S, Zhu Y, Wu W, Zhang Q, Wang Y, Wang Z, Yang F. A correlation study of intestinal microflora and first-episode depression in Chinese patients and healthy volunteers. Brain Behav. 2021;11(8):e02036. https://doi.org/10.1002/brb3.2036

Shen CL, Wang R, Ji G, Elmassry MM, Zabet-Moghaddam M, Vellers H, Hamood AN, Gong X, Mirzaei P, Sang S, Neugebauer V. Dietary supplementation of gingerols- and shogaols-enriched ginger root extract attenuate pain-associated behaviors while modulating gut microbiota and metabolites in rats with spinal nerve ligation. J Nutr Biochem. 2022;100:108904. https://doi.org/10.1016/j.jnutbio.2021.108904

Liu CS, Liang X, Wei XH, Jin Z, Chen FL, Tang QF, Tan XM. Gegen qinlian decoction treats diarrhea in piglets by modulating gut microbiota and short-chain fatty acids. Front Microbiol. 2019;10:825. https://doi.org/10.3389/fmicb.2019.00825

Takagi T, Naito Y, Higashimura Y, Ushiroda C, Mizushima K, Ohashi Y, Yasukawa Z, Ozeki M, Tokunaga M, Okubo T, Katada K, Kamada K, Uchiyama K, Handa O, Itoh Y, Yoshikawa T. Partially hydrolysed guar gum ameliorates murine intestinal inflammation in association with modulating luminal microbiota and SCFA. Br J Nutr. 2016;116(7):1199-205. https://doi.org/10.1017/S0007114516003068

Zheng DW, Li RQ, An JX, Xie TQ, Han ZY, Xu R, Fang Y, Zhang XZ. Prebiotics-encapsulated probiotic spores regulate gut microbiota and suppress colon cancer. Adv Mater. 2020;32(45):e2004529. https://doi.org/10.1002/adma.202004529

Lanza M, Filippone A, Ardizzone A, Casili G, Paterniti I, Esposito E, Campolo M. SCFA treatment alleviates pathological signs of migraine and related intestinal alterations in a mouse model of NTG-induced migraine. Cells. 2021;10(10):2756. https://doi.org/10.3390/cells10102756

Huang X, Su S, Duan JA, Sha X, Zhu KY, Guo J, Yu L, Liu P, Shang E, Qian D. Effects and mechanisms of Shaofu-Zhuyu decoction and its major bioactive component for Cold - Stagnation and Blood - Stasis primary dysmenorrhea rats. J Ethnopharmacol. 2016;186:234-43. https://doi.org/10.1016/j.jep.2016.03.067

Wu Y, Li K, Zeng M, Qiao B, Zhou B. Serum metabolomics analysis of the anti-inflammatory effects of gallic acid on rats with acute inflammation. Front Pharmacol. 2022;13:830439. https://doi.org/10.3389/fphar.2022.830439

Yu Y, Villalobos-Hernandez EC, Pradhananga S, Baker CC, Keating C, Grundy D, Lomax AE, Reed DE. Deoxycholic acid activates colonic afferent nerves via 5-HT3 receptor-dependent and -independent mechanisms. Am J Physiol Gastrointest Liver Physiol. 2019;317(3):G275-84. https://doi.org/10.1152/ajpgi.00016.2019

Zhou F, Wang X, Han B, Tang X, Liu R, Ji Q, Zhou Z, Zhang L. Short-chain fatty acids contribute to neuropathic pain via regulating microglia activation and polarization. Mol Pain. 2021;17:1744806921996520. https://doi.org/10.1177/1744806921996520

Zhang W, Wang F, Zhang L, Sun T, Fu Z. Intrathecal injection of ozone alleviates CCI‑induced neuropathic pain via the GluR6‑NF‑κB/p65 signalling pathway in rats. Mol Med Rep. 2021;23(4):231. https://doi.org/10.3892/mmr.2021.11870

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Published

2025-10-02

How to Cite

1.
Meng H, Yu H, Gang S, Bo A, Wang Z. Therapeutic effects of Mongolian medical warm acupuncture on neuropathic pain via gut microbiota and inflammatory pathway regulation in a chronic constriction injury rat model. Arch Biol Sci [Internet]. 2025Oct.2 [cited 2025Dec.5];77(3):225-36. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/11090

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Vol. 77 No. 3 (2025)

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Articles

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Copyright (c) 2025 Husileng Meng, Hong Yu, Suhe Gang, Gula A, Zhanli Wang

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