Electroacupuncture induces analgesia by regulating spinal synaptic plasticity via the AMPA/NMDA receptor in a model of cervical spondylotic radiculopathy: secondary analysis of an experimental study in rats
Authors: Wang Tian , Chen Hai-Yan , Yang Pu , Zhang Xi , Su Sheng-Yong 
Published: February 2025

Objective:

Cervical spondylotic radiculopathy (CSR) is characterized by neuropathic pain (NP). Although the analgesic effect of electroacupuncture (EA) has been widely recognized in clinical practice, the mechanism of EA in the treatment of CSR remains unknown. We previously reported that 7 days of EA improved behavioral markers of NP, attenuated increases in α-synuclein, synapsin 1 and 2, postsynaptic density (PSD)-95 and growth-associated protein (GAP)-43, and improved ultrastructural changes within synapses in a rat model of CSR. Herein, we present supplemental data from the same cohort of animals examining the timing of behavioral improvement within the first week (through additional measurements at 3 and 5 days into the EA treatment) and new data on the effects of EA on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-d-aspartic acid receptor (NMDAR) levels.

Methods:

As previously reported, the rats were divided into four groups at random: normal, sham, CSR and CSR + EA. EA at bilateral LI4 and LR3 was administered once a day for 7 days (20 min each) in the CSR + EA group after the CSR model was established by inserting a fishing line under the laminae. Behavioral assessments were carried out prior to initiation of EA and at 3, 5 and 7 days into the 7-day treatment course. Concentrations ofγ-aminobutyric acid (GABA) and glutamate (Glu) were determined using enzyme-linked immunosorbent assay and ultraviolet colorimetry, respectively, and AMPAR (glutamate receptor (GluR)1 and GluR2 membrane protein) expression was determined using Western blotting. Immunohistochemistry was used to detect the protein expression and average optical density (AOD) of NMDAR1 (NR1), NMDAR2A (NR2A) and NMDAR2B (NR2B). Quantitative reverse transcription-polymerase chain reaction was used to detect the mRNA expression of NR1, NR2A and NR2B. Transmission electron microscopy was used to observe changes in synaptic ultrastructure.

Results:

EA significantly improved the pressure pain threshold (PPT) and mechanical withdrawal threshold (MWT) 5 days into the intervention, although effects were less pronounced than at 7 days (at completion of treatment). However, significant effects on gait scores were not seen prior to 7 days. As previously reported, EA also improved markers of synaptic ultrastructure. In the spinal cord, GluR1 membrane protein expression was decreased, GluR2 membrane protein expression was increased, and the GluR1/GluR2 ratio was decreased. Protein and mRNA expression of NR1, NR2A and NR2B was significantly decreased. GABA concentration was markedly increased, while Glu concentration was markedly decreased.

Conclusion:

Evidence of EA analgesia (higher PPT and MWT scores) was seen after 5 days of EA, while positive effects on motor function required 7 days of treatment. The underlying mechanism may be related to inhibition of AMPAR and NMDAR expression, regulation of the concentration of related neurotransmitters and improvement of spinal cord synaptic plasticity. This study establishes a preliminary theoretical foundation for the use of EA in the clinical treatment of CSR.