Dexmedetomidine alleviated neuropathic pain in dorsal root ganglion neurons by inhibition of anaerobic glycolysis activity and enhancement of ROS tolerance.

Peibin Liu,Xinjin Chi,Jiaxin Chen,Lei Zheng,Fang Tan,Jingling Tian,Tufeng Chen,Yingqing Deng

doi:10.1042/bsr20191994

Abstract

Neuropathic pain is a kind of chronic pain that is triggered or caused primarily by damage to the nervous system and neurological dysfunction. It’s known that dexmedetomidine is a new type of highly selective alpha2-adrenoceptor agonist with sedation, anti-anxiety, analgesic and other effects. However, the function and mechanism of dexmedetomidine on neuropathic pain are not clear. Rat DRG neurons were isolated and identified using immunofluorescence assay. Following treatment with H2O2, dexmedetomidine or ROS inhibitor (NAC), the apoptosis and ROS levels were examined by flow cytometery; apoptosis- and anaerobic glycolysis-related proteins were determined by Western blot assay; glucose consumption, pyruvic acid, lactic acid and ATP/ADP ratios were also measured. The results revealed that dexmedetomidine inhibited H2O2-induced apoptosis and reactive oxygen species (ROS) in rat DRG neurons and in addition, dexmedetomidine down-regulated the expression levels of anaerobic glycolysis-related proteins, significantly reduced glucose, pyruvic acid and lactic acid levels. It also increased the ATP/ADP ratio in H2O2-treated rat dorsal root ganglion (DRG) neurons. Moreover, we also demonstrated that ROS inhibitor (NAC) also inhibited H2O2-induced apoptosis and anaerobic glycolysis in rat DRG neurons. In conclusion, dexmedetomidine suppressed H2O2-induced apoptosis and anaerobic glycolysis activity by inhibiting ROS, in rat DRG neurons. Therefore, dexmedetomidine might play a pivotal role in neuropathic pain by the inhibition of ROS.

Highlights

Neuropathic pain refers to the douleur anormale, caused by damage and dysfunction of the central or peripheral nervous system [1,2]
The results revealed that dexmedetomidine could inhibit dorsal root ganglion (DRG) neuron proliferation, and the IC50 of dexmedetomidine was 208.4 μM (Figure 1C)
Studies using animal model have demonstrated that neuropathic pain induced by peripheral nerve injury is often accompanied by apoptosis of spinal DRG neurons [30,31]

Summary

Introduction

Neuropathic pain refers to the douleur anormale (abnormal pain), caused by damage and dysfunction of the central or peripheral nervous system [1,2]. The treatment of neuropathic pain is mainly through drug therapy, while there are a number of side effects, and the curative effect is low [6]. Only 30–40% of patients have greater than 50% pain relief from medication [7]. This shows that the therapeutic modes of neuropathic pain are not ideal in clinical practice. Exploring the pathogenesis of neuropathic pain might provide reliable basis and important medical insights into the treatment of pain. There is a growing body of studies indicating that apoptosis of dorsal root ganglion (DRG) neurons is involved in the development of neuropathic pain [8], but its mechanism is still unclear

Methods

Results

Conclusion