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Peer-reviewedCC BY-NC 4.0Journal of Pain Research

Electroacupuncture Attenuates Neuroinflammation and Improves Metabolic Dysregulation in a Mouse Model of Painful Diabetic Peripheral Neuropathy: A Multi-Omics Study

7 affiliations
  1. 1College of Acupuncture and Massage, Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of China
  2. 2Department of Endocrinology, Metabolism and Gastroenterology, Third Affiliated Clinical Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of China
  3. 3College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of China
  4. 4Northeast Asia Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of China
  5. 5Public Experimental Center, Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of China
  6. 6Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China
  7. 7Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of China

Abstract

Background: Painful diabetic peripheral neuropathy (PDPN) is a complication of diabetes characterized by neuropathic pain, with metabolic dysfunction and neuroinflammation implicated in its pathophysiology. Although electroacupuncture (EA) may alleviate neuropathic pain, its broader effects in PDPN remain unclear.

Methods: PDPN was induced by high-fat feeding and repeated streptozotocin injections. Two independent experiments (n = 10 mice/group) included Control, PDPN, and EA groups; Experiment 2 additionally included EA+capsaicin and EA+vehicle groups. Capsaicin was given after each of the final four EA treatments to examine transient receptor potential vanilloid 1 (TRPV1)-related responses. After model confirmation, PDPN mice were re-randomized into groups and randomly allocated within groups for subsequent analyses. EA was applied at ST36, BL13, BL20, BL23, and SP6. Pain behavior, nerve conduction, histopathology, and inflammatory and metabolic markers were assessed. Additionally, sciatic nerve transcriptomic and untargeted metabolomic data were integrated by pathway-based network analysis.

Results: EA improved pain-related behavior and sciatic nerve conduction velocity. On day 75, thermal withdrawal latency (TWL) increased by 5.59 s (95% confidence interval [CI], 4.35–6.83; Cohen’s d = 4.23) and mechanical withdrawal threshold (MWT) by 0.95 g (95% CI, 0.79–1.12; Cohen’s d = 5.39) versus PDPN mice. EA also attenuated sciatic nerve pathological and inflammatory changes in PDPN mice, lowered dorsal root ganglion TRPV1 protein levels by 54.2% (n = 3/group), reduced spinal glial-associated inflammatory immunoreactivity, and improved relevant metabolic indicators. Capsaicin partially attenuated several of these EA-associated responses, providing supportive but not definitive evidence for TRPV1 involvement. Multi-omics analyses revealed exploratory associations involving lipid, energy, and redox metabolism.

Conclusion: EA reduced pain hypersensitivity and improved nerve function alongside neuroinflammatory and metabolic changes in PDPN mice. And multi-omics findings generate hypotheses about metabolic processes associated with EA treatment, but their causal contributions to analgesia require further investigation.

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BibTeX
@article{wang2026electroacupuncture,
  title = {{Electroacupuncture Attenuates Neuroinflammation and Improves Metabolic Dysregulation in a Mouse Model of Painful Diabetic Peripheral Neuropathy: A Multi-Omics Study}},
  author = {Qi Wang and Xinyu Zhang and Dan Wang and Yilin Chai and Mengyuan Li and Mengmeng Sun and Long Wang and Xinyan Gao and Hongfeng Wang},
  journal = {Journal of Pain Research},
  year = {2026},
  month = oct,
  doi = {10.2147/jpr.s646097},
  url = {https://doi.org/10.2147/jpr.s646097},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Electroacupuncture Attenuates Neuroinflammation and Improves Metabolic Dysregulation in a Mouse Model of Painful Diabetic Peripheral Neuropathy: A Multi-Omics Study
AU  - Qi Wang
AU  - Xinyu Zhang
AU  - Dan Wang
AU  - Yilin Chai
AU  - Mengyuan Li
AU  - Mengmeng Sun
AU  - Long Wang
AU  - Xinyan Gao
AU  - Hongfeng Wang
PY  - 2026
DA  - 2026/10/31
JO  - Journal of Pain Research
DO  - 10.2147/jpr.s646097
UR  - https://doi.org/10.2147/jpr.s646097
AB  - Background: Painful diabetic peripheral neuropathy (PDPN) is a complication of diabetes characterized by neuropathic pain, with metabolic dysfunction and neuroinflammation implicated in its pathophysiology. Although electroacupuncture (EA) may alleviate neuropathic pain, its broader effects in PDPN remain unclear.  Methods: PDPN was induced by high-fat feeding and repeated streptozotocin injections. Two independent experiments (n = 10 mice/group) included Control, PDPN, and EA groups; Experiment 2 additionally included EA+capsaicin and EA+vehicle groups. Capsaicin was given after each of the final four EA treatments to examine transient receptor potential vanilloid 1 (TRPV1)-related responses. After model confirmation, PDPN mice were re-randomized into groups and randomly allocated within groups for subsequent analyses. EA was applied at ST36, BL13, BL20, BL23, and SP6. Pain behavior, nerve conduction, histopathology, and inflammatory and metabolic markers were assessed. Additionally, sciatic nerve transcriptomic and untargeted metabolomic data were integrated by pathway-based network analysis.  Results: EA improved pain-related behavior and sciatic nerve conduction velocity. On day 75, thermal withdrawal latency (TWL) increased by 5.59 s (95% confidence interval [CI], 4.35–6.83; Cohen’s d = 4.23) and mechanical withdrawal threshold (MWT) by 0.95 g (95% CI, 0.79–1.12; Cohen’s d = 5.39) versus PDPN mice. EA also attenuated sciatic nerve pathological and inflammatory changes in PDPN mice, lowered dorsal root ganglion TRPV1 protein levels by 54.2% (n = 3/group), reduced spinal glial-associated inflammatory immunoreactivity, and improved relevant metabolic indicators. Capsaicin partially attenuated several of these EA-associated responses, providing supportive but not definitive evidence for TRPV1 involvement. Multi-omics analyses revealed exploratory associations involving lipid, energy, and redox metabolism.  Conclusion: EA reduced pain hypersensitivity and improved nerve function alongside neuroinflammatory and metabolic changes in PDPN mice. And multi-omics findings generate hypotheses about metabolic processes associated with EA treatment, but their causal contributions to analgesia require further investigation.
SN  - 1178-7090
ER  -