Nanoparticle-Encapsulated Curcumin Inhibits Diabetic Neuropathic Pain Involving the P2Y12 Receptor in the Dorsal Root Ganglia.

Tianyu Jia,Shangdong Liang,Lifang Zou,Shuangmei Liu,Chunping Zhang,Guilin Li,Jingan Rao,Huilong Yuan,Shanhong Zhao,Liran Shi,Bing Wu,Zhihua Yi,Yun Gao,Lin Li,Hong Xu,Hui Liu

doi:10.3389/fnins.2017.00755

Abstract

Diabetic peripheral neuropathy results in diabetic neuropathic pain (DNP). Satellite glial cells (SGCs) enwrap the neuronal soma in the dorsal root ganglia (DRG). The purinergic 2 (P2) Y12 receptor is expressed on SGCs in the DRG. SGC activation plays an important role in the pathogenesis of DNP. Curcumin has anti-inflammatory and antioxidant properties. Because curcumin has poor metabolic stability in vivo and low bioavailability, nanoparticle-encapsulated curcumin was used to improve its targeting and bioavailability. In the present study, our aim was to investigate the effects of nanoparticle-encapsulated curcumin on DNP mediated by the P2Y12 receptor on SGCs in the rat DRG. Diabetic peripheral neuropathy increased the expression levels of the P2Y12 receptor on SGCs in the DRG and enhanced mechanical and thermal hyperalgesia in rats with diabetes mellitus (DM). Up-regulation of the P2Y12 receptor in SGCs in the DRG increased the production of pro-inflammatory cytokines. Up-regulation of interleukin-1β (IL-1β) and connexin43 (Cx43) resulted in mechanical and thermal hyperalgesia in rats with DM. The nanoparticle-encapsulated curcumin decreased up-regulated IL-1β and Cx43 expression and reduced levels of phosphorylated-Akt (p-Akt) in the DRG of rats with DM. The up-regulation of P2Y12 on SGCs and the up-regulation of the IL-1β and Cx43 in the DRG indicated the activation of SGCs in the DRG. The nano-curcumin treatment inhibited the activation of SGCs accompanied by its anti-inflammatory effect to decrease the up-regulated CGRP expression in the DRG neurons. Therefore, the nanoparticle-encapsulated curcumin treatment decreased the up-regulation of the P2Y12 receptor on SGCs in the DRG and decreased mechanical and thermal hyperalgesia in rats with DM.

Highlights

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia (Whiting et al, 2011; Tesfaye and Selvarajah, 2012; Ma and Chan, 2013; Xu et al, 2013; Zychowska et al, 2013)
The dorsal root ganglia (DRG) plays an important role in the processing and transmission of diabetic neuropathic pain (DNP) signals (Hanani et al, 2014; Liu et al, 2016; Li et al, 2017; Peng et al, 2017)
The expression of P2Y12 receptor was increased in the DRG of DM rats compared with that in control rats

Summary

Introduction

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia (Whiting et al, 2011; Tesfaye and Selvarajah, 2012; Ma and Chan, 2013; Xu et al, 2013; Zychowska et al, 2013). Diabetic peripheral neuropathy is the most common complication of T2DM and results in sensory symptoms, including diabetic neuropathic pain (DNP) (Morales-Vidal et al, 2012; Singh et al, 2014). Elevated levels of inflammation are associated with the development of DNP (Pop-Busui et al, 2016). The currently prescribed drugs are not satisfactory as treatments for DNP (Callaghan et al, 2012; Zychowska et al, 2013; Albers and Pop-Busui, 2014). Numerous studies have tried to develop improved pain-relieving treatments (Callaghan et al, 2012; Zychowska et al, 2013; Albers and PopBusui, 2014). Drugs that target low-grade inflammation may be useful for relieving DNP

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