Electroacupuncture at Zusanli (ST36) alleviates paclitaxel-induced neuropathic pain in rats via regulating TLR4 signaling pathway in the spinal cord

电针刺激足三里穴(ST36)可通过调节脊髓中的TLR4信号通路缓解紫杉醇诱导的大鼠神经性疼痛

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Abstract

Paclitaxel (PTX) treatment induces a pathological pain state that is often associated with neuroinflammation in the central nervous system. The available interventions for PTX-induced pathological pain encounter adverse effects and limited efficacies. Recent studies have shown the significant effectiveness of Electroacupuncture (EA) in pain management as a simple and safe alternative medical treatment. Here, we evaluated the analgesic effect of EA on pain behaviors in PTX-treated rats and investigated its potential analgesic mechanisms. In this study, a pathological pain model was established in SD rats via intraperitoneal (i.p.) injection of PTX. EA or Sham EA treatments were applied every other day for PTX-treated rats. Pain behaviors of mechanical allodynia and thermal hyperalgesia in rats were measured, followed by analysis of the spinal cord tissue via using molecular biology methods. Here, we show that EA treatment is capable to alleviate PTX-induced mechanical allodynia and thermal hyperalgesia in rats. In addition, EA regulated the abnormal protein expression of astrocytes, microglia, neurons, TLR4-MyD88/TRIF signaling pathway and cytokines in the lumbar spinal cord of PTX-treated rats. Furthermore, we investigated the spinal co-expressions of TLR4 in astrocytes, microglia, and neurons respectively in rats and the regulatory effect of EA on TLR4 and cells mentioned above. In summary, EA shows analgesic properties as it ameliorates PTX-induced mechanical allodynia and thermal hyperalgesia probably by reducing central neuroinflammation. Therefore, we consider EA as a potential therapeutic candidate for the treatment of PTX-induced pathologic pain. Notably, this study provides the first morphological evidence that EA may concurrently influence TLR4-mediated neuroimmune interactions across multiple spinal cell types, suggesting a potential central mechanism distinct from previously reported peripheral actions.

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