Involvement of the astroglial glutamate–glutamine cycle in the analgesic effects of electroacupuncture in a rat model of chronic neuropathic pain
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Objective: Our previous study found that astrocytes are involved in cumulative analgesia; however, the underlying mechanism remains unclear. The aim of this study was to further explore the potential role of astrocytes in the effects of electroacupuncture (EA) on neuropathic pain by focusing on the glutamate–glutamine cycle. Methods: 69 male Sprague–Dawley (SD) rats were randomly divided into a normal control group, untreated chronic constriction injury (CCI) model group and EA-treated model (CCI + EA) group. EA was applied bilaterally at ST36 and GB34. Pain thresholds were assessed using behavioral tests and thermal stimuli. We examined the co-expression of glutamate/aspartate transporter (GLAST) via immunofluorescence and measured the expression levels of GLAST, glutamate transporter (GLT)-1 and glutamine synthetase (GS) using Western blotting and polymerase chain reaction (PCR). Glutamate (Glu) and gamma-aminobutyric acid (GABA) levels were detected by high-performance liquid chromatography (HPLC). To validate the impact of GLAST/GLT-1 in the analgesic effect of EA, an additional 30 SD male rats were divided into groups receiving intrathecal saline, GLAST antagonist or GLT-1 antagonist alongside EA. Results: Post-CCI, pain thresholds were decreased, GLAST expression was diminished, and spinal Glu levels were increased. EA treatment reversed these effects, improved pain thresholds and GLAST/GLT-1 expression in astrocytes, and reduced Glu levels. Antagonist administration negated the analgesic effects of EA. Conclusion: Repeated EA administration inhibited CCI-induced chronic neuropathic pain in rats, corresponding to a reversal of decreased expression of GLAST and GLT-1, which may have accelerated the clearance of Glu and thereby reduced its concentration. Regulation of the astroglial glutamate–glutamine cycle is a potential target of EA.
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Astrocytes are implicated in neuropathic pain mediated by the Glu-Gln cycle.
“Astrocytes have been implicated in neuropathic pain mediated by the Glu–Gln cycle”
From Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization (2026) · cites this paper as [173]
Cites
Pain and the global burden of disease
Rice, A. S. C., Smith, B. H., & Blyth, F. M. (2016) · Pain · doi:10.1097/j.pain.0000000000000454 · Cited by 498 · see citing works
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Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization
Lai, W., Tang, X., Chen, S., Zhou, Y., Qi, Z., Cao, M., Yuan, C., Yu, J., & Wen, C. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1677310 · Cited by 4 · see citing works
“Astrocytes have been implicated in neuropathic pain mediated by the Glu – Gln cycle; however, whether astrocytes can modulate NP through Glu/GluR-mediated synaptic plasticity remains unclear (173).”
- Authors
- Zhu, H.-H., Song, X.-K., Zhang, J.-L., Zhang, J.-L., Rong, P.-J., & Wang, J.-Y.
- Affiliations
- Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China
- China Academy of Chinese Medical Sciences (CN)
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China
- Venue
- Acupuncture in Medicine
- Publisher
- SAGE Publications
- Published
- 2024-12-30
- Volume
- 43
- Issue
- 1
- Pages
- 14-25
- ISSN
- 0964-5284 (ISSN-L)
- 1759-9873
- OpenAlex
- W4405917747
- Cited by
- 6
- References
- 1
- Citations by year
- 2026: 4 · 2025: 2
- FWCI
- 1.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Acupuncture in Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- natural science foundation of beijing municipality
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Acupuncture Treatment Research Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- electroacupuncture, chronic neuropathic pain, astrocytes, glutamate-glutamine cycle, GLT-1, GLAST, glutamine synthetase, glutamate, GABA, chronic constriction injury, Zusanli (ST36), GB34, analgesia
- MeSH terms
- Animals, Astrocytes, Disease Models, Animal, Glutamine, Glutamate-Ammonia Ligase, Humans, Male, Neuralgia, Acupuncture Analgesia, Acupuncture Points, Electroacupuncture, Rats, Sprague-Dawley, Pain Threshold, Glutamic Acid, Excitatory Amino Acid Transporter 1, Excitatory Amino Acid Transporter 2, Rats, Chronic Pain
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