Acupotomy Alleviates Pain and Attenuates Spinal Neuronal Hyperexcitability in Knee Osteoarthritis Rats: Implication of the CaMKII/GluA1 Axis.
4 affiliations
- 1School of Acupuncture, Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
- 2Department of Acupuncture and Moxibustion, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei, People's Republic of China.
- 3Department of Acupuncture and Physiotherapy, Beijing Electric Power Hospital of State Grid Corporation of China, Beijing, People's Republic of China.
- 4School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
Abstract
Objective
To investigate the spinal mechanisms underlying the analgesic effects of acupotomy on chronic pain and central sensitization in rats with monosodium iodoacetate (MIA)-induced knee osteoarthritis (KOA).Methods
Following MIA-induced KOA and a three-week acupotomy intervention in rats, pain behaviors and joint pathology were assessed. Spinal RNA-sequencing was performed to identify differentially expressed genes. Key targets (CaMKII and GluA1) were validated at both mRNA and protein levels using RT-qPCR and Western blotting. Furthermore, immunofluorescence and whole-cell patch-clamp electrophysiology were employed to evaluate the activation and excitability of spinal substantia gelatinosa (SG) neurons.Results
Acupotomy significantly alleviated mechanical and thermal hyperalgesia and reduced joint degeneration in KOA rats. RNA-seq analysis revealed the modulation of 220 genes in the spinal cord. These DEGs were significantly enriched in calcium signaling and synaptic transmission pathways, highlighting CaMKII and Gria1 as potential key molecules. Molecular validations confirmed that acupotomy downregulated CaMKII and Gria1 mRNA expression and the phosphorylation ratios of CaMKII and GluA1. Furthermore, acupotomy reduced the activation of p-CaMKII-positive neurons in the spinal SG region and dampened their abnormally high-frequency action potential discharges.Conclusion
Acupotomy intervention ameliorates peripheral joint degeneration and exerts significant analgesia in KOA, which is accompanied by a reduction in the intrinsic hyperexcitability of spinal SG neurons. Although direct causal validation utilizing targeted inhibitors is warranted, our findings suggest that this analgesic effect is closely associated with the downregulation of the CaMKII/GluA1 signaling axis, providing a plausible central mechanistic framework.
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BibTeX
@article{wu2026acupotomy,
title = {{Acupotomy Alleviates Pain and Attenuates Spinal Neuronal Hyperexcitability in Knee Osteoarthritis Rats: Implication of the CaMKII/GluA1 Axis.}},
author = {Meng Wu and Jinyan Teng and Ziyi Huang and Ruizhe Xu and Xiaoming Gao and Xin Hao and Zhigang Li and Zhaoheng Liu},
journal = {Journal of pain research},
year = {2026},
month = oct,
doi = {10.2147/jpr.s633426},
url = {https://europepmc.org/article/MED/42898890},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Acupotomy Alleviates Pain and Attenuates Spinal Neuronal Hyperexcitability in Knee Osteoarthritis Rats: Implication of the CaMKII/GluA1 Axis.
AU - Meng Wu
AU - Jinyan Teng
AU - Ziyi Huang
AU - Ruizhe Xu
AU - Xiaoming Gao
AU - Xin Hao
AU - Zhigang Li
AU - Zhaoheng Liu
PY - 2026
DA - 2026/10/15
JO - Journal of pain research
DO - 10.2147/jpr.s633426
UR - https://europepmc.org/article/MED/42898890
AB - Objective To investigate the spinal mechanisms underlying the analgesic effects of acupotomy on chronic pain and central sensitization in rats with monosodium iodoacetate (MIA)-induced knee osteoarthritis (KOA).Methods Following MIA-induced KOA and a three-week acupotomy intervention in rats, pain behaviors and joint pathology were assessed. Spinal RNA-sequencing was performed to identify differentially expressed genes. Key targets (CaMKII and GluA1) were validated at both mRNA and protein levels using RT-qPCR and Western blotting. Furthermore, immunofluorescence and whole-cell patch-clamp electrophysiology were employed to evaluate the activation and excitability of spinal substantia gelatinosa (SG) neurons.Results Acupotomy significantly alleviated mechanical and thermal hyperalgesia and reduced joint degeneration in KOA rats. RNA-seq analysis revealed the modulation of 220 genes in the spinal cord. These DEGs were significantly enriched in calcium signaling and synaptic transmission pathways, highlighting CaMKII and Gria1 as potential key molecules. Molecular validations confirmed that acupotomy downregulated CaMKII and Gria1 mRNA expression and the phosphorylation ratios of CaMKII and GluA1. Furthermore, acupotomy reduced the activation of p-CaMKII-positive neurons in the spinal SG region and dampened their abnormally high-frequency action potential discharges.Conclusion Acupotomy intervention ameliorates peripheral joint degeneration and exerts significant analgesia in KOA, which is accompanied by a reduction in the intrinsic hyperexcitability of spinal SG neurons. Although direct causal validation utilizing targeted inhibitors is warranted, our findings suggest that this analgesic effect is closely associated with the downregulation of the CaMKII/GluA1 signaling axis, providing a plausible central mechanistic framework.
SN - 1178-7090
ER -