Electroacupuncture ameliorates pain in cervical spondylotic radiculopathy rat by inhibiting the CaMKII/CREB/BDNF signaling pathway and regulating spinal synaptic plasticity

Abstract

BackgroundCentral sensitization is one of the important mechanisms underlying neuropathic and radicular pain due to cervical spondylotic radiculopathy (CSR). Recent studies have shown that the calmodulin‐dependent protein kinase II (CaMKII)/cAMP‐response element binding protein (CREB)/brain‐derived neurotrophic factor (BDNF) signaling pathway mediates central sensitization through its involvement in spinal cord synaptic plasticity. Our group has previously found that electroacupuncture (EA) has a good analgesic effect on CSR. However, the central analgesic mechanism of EA for CSR is not yet clear.MethodsThe rats were randomly divided into Blank group, Sham‐operated group, CSR group, and EA group. We prepared the CSR rat model using the fish wire extrusion method. The behavioral and mechanical pain thresholds of the rats in each group were measured 5 days after successful modeling and 7 days after the intervention. The first intervention was started 5 days after successful modeling, and the EA group was treated by acupuncture at the bilateral LI4 and LR3 points on the same side as one group, connected to a G6805‐I electroacupuncture apparatus with continuous waves at 1.5 Hz. The remaining groups were not subjected to EA intervention. The treatment was administered once a day for 7 consecutive days and then executed. We used WB, immunofluorescence, and qRT‐PCR to detect the expression of CaMKII/CREB/BDNF signaling pathway‐related factors in the synaptic of rat spinal cord in each group.ResultsEA improved pain threshold and motor function in CSR rats, inhibited the expression of BDNF, P‐TrkB, CAMKII, and P‐CREB in spinal cord synapses, reduced the expression of pain factor c‐fos and postsynaptic membrane protein molecule neuroligin2, exerted a modulating effect on spinal cord synaptic plasticity in CSR rats, and suppressed the overactive synaptic efficacy.ConclusionEA mediates central sensitization and exerts analgesic effects on CSR by modulating spinal synaptic plasticity, which may be related to the inhibition of CaMKII/CREB/BDNF signaling pathway.

Acupuncture for radicular pain: a review of analgesic mechanism

“…The rat autogenous nucleus pulposus grafting model, a non-compressive simulation of lumbar disk nucleus pulposus protrusion, has shown that such protrusion can lead to nerve root damage and subsequent radicular pain ( Kayama et al, 1996 ; Lu et al, 2003 ). Recent studies ( Su H. et al, 2023 ; Zhang et al, 2023 ) have demonstrated that this model results in significantly elevated serum levels of IL-1β, IL-6, IL-8 and NF-κB, along with increased expression of RAGE protein, HMGB1 protein and mRNA in spinal nerve trunk tissue. Remarkably, after 14 days of acupuncture treatment, there were significant reductions in the serum levels of IL-1β, IL-6, IL-8, and NF-κB, as well as in the expression of RAGE protein, HMGB1 protein and mRNA within spinal nerve trunk tissue in the treatment group compared to the control group.…”