Analgesic effects of electroacupuncture via the EphBs-p38 MAPK signaling pathway and microglial suppression in the chronic constriction injury rat model of neuropathic pain

Objective: To explore the analgesic effects of electroacupuncture (EA) and its impact on the EphBs-p38 mitogen-activated protein kinase (MAPK) pathway and microglia in a rat model of neuropathic pain (NP). Methods: Following adaptive training, 60 male Sprague Dawley (SD) rats were allocated to one of two experiments. In experiment 1, rats received intrathecal SB203580 (p38 MAPK inhibitor), intramuscular EphB1-Fc (EphBs inhibitor) or no injection before undergoing chronic constrictive injury (CCI). In experiment 2, CCI model rats received EA either alone or combined with either anisomycin (p38 MAPK agonist) or EphrinB1-Fc (EphBs agonist) versus minimal acupuncture (MA) as a control intervention. A sham surgery group was included in both experiments as a control for CCI. All groups consisted of n = 6 rats (four in experiment 1 and six in experiment 2). Behavioral hyperalgesia was examined and the spinal L5-6 region was harvested and subjected to enzyme-linked immunosorbent assay to assess tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels. Western blotting and immunofluorescence were used to assess protein expression of B-cell lymphoma (Bcl)-2, Bcl-2 associated X-protein (BAX), EphB1, EphrinB1, p38 MAPK, phosphorylated (p)-p38 MAPK and ionized calcium binding adaptor molecule (Iba)-1. Results: CCI induced behavioral hyperalgesia, as demonstrated by altered paw withdrawal latency (PWL), paw withdrawal threshold (PWT) and cytokine levels, and increased p38 MAPK phosphorylation and microglial activation. However, inhibitors SB203580 and EphB1-Fc reversed these effects. Notably, EA showed similar beneficial effects, but these were counteracted when combined with anisomycin and EphrinB1-Fc. Conclusions: The analgesic effects of EA in this rat model of NP appear to be linked to diminished p-p38 MAPK expression and subsequent microglial deactivation. EA has a potential role as a complementary therapy for NP.