Effect of electro-acupuncture on the BDNF-TrkB pathway in the spinal cord of CCI rats.

Microglia, which comprise a sensor for pathological events in the central nervous system, may be triggered by nerve injury and transformed from a quiescent state into an activated state; ionised calcium binding adaptor molecule 1 (Iba1) is a sensitive marker associated with activated microglia. Accumulated evidence suggests that spinal activated microglia and the brain-derived neurotrophic factor (BDNF)-tyrosine kinase receptor B (TrkB) signalling pathway play major roles in the production and development of neuropathic pain. Electro-acupuncture (EA) has a positive effect on relieving chronic neuropathic pain; however, the underlying mechanisms remain unclear. To determine the significance of EA in the treatment of neuropathic pain mediated by activated microglia and the BDNF-TrkB signalling pathway in the spinal cord, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values were recorded to assess hyperalgesia and allodynia. In addition, the amount of activated microglia and BDNF were assessed via immunofluorescence. Iba1, BDNF and TrkB mRNA expression levels were examined using qPCR; the protein levels of BDNF, p-TrkB and TrkB in the spinal cord were analysed via western blotting. The present study demonstrated that EA treatment increased the MWT and TWL values. EA significantly inhibited the proportion of activated microglia and BDNF expression in the spinal cord after chronic constrictive injury (CCI). Furthermore, EA decreased the expression of BDNF and TrkB at both the mRNA and protein levels in the spinal cord of CCI rats. These findings suggest that the analgesic effect of EA may be achieved by inhibiting the activation of spinal microglia and subsequently blocking the BDNF-TrkB signalling pathway.

KCC2-GABAA pathway correlates with the analgesic effect of electro-acupuncture in CCI rats.

Potassium-chloride cotransporter 2 (KCC2) has been indicated to serve a crucial role during chronic neuropathic pain (NP). Following the emergence of NP, γ­aminobutyric acid (GABA) A receptor­mediated signaling may be further impaired by the changes of KCC2 chloride anion gradient. In the present study, the authors investigate the effect of electro-acupuncture (EA) on the behavior and the expression of KCC2 and GABAA receptor γ2 subunit in the spinal cord of chronic constriction injury (CCI) model rats. A total of 60 adult male Sprague­Dawley rats were divided into four groups: Normal group, sham­CCI group, CCI group and CCI+EA group. The effect of EA was assessed via the values of mechanical withdrawal threshold and thermal withdrawal latency, which were significantly improved upon stimulation of the ST­36 and GB­34 acupoints. In addition, a marked reduction in both the mRNA and protein levels of KCC2 and GABAA receptor γ2 subunit was observed in the spinal cord following loose ligation of the sciatic nerve. The reductions in KCC2 and GABAA receptor γ2 subunit expression were reversed by EA treatment. These results support the notion that KCC2 and GABAA receptor γ2 subunit contribute to NP following peripheral nerve injury and extend the understanding of the analgesic effects of EA on NP.