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Nanoparticle-encapsulated emodin decreases diabetic neuropathic pain probably via a mechanism involving P2X3 receptor in the dorsal root ganglia

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Abstract

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus (DM). More than 90% of all cases of DM belong to type 2 diabetes mellitus (T2DM). Emodin is the main active component of Radix et rhizoma rhei and has anti-bacterial, anti-viral, anti-ulcerogenic, anti-inflammatory, and anti-cancer effects. Nanoparticle encapsulation of drugs is beneficial for drug targeting and bioavailability as well as for lowering drug toxicity side effects. The aim of this study was to investigate the effects of nanoparticle-encapsulated emodin (nano emodin) on diabetic neuropathic pain (DNP) mediated by the Purin 2X3 (P2X3) receptor in the dorsal root ganglia (DRG). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values in T2DM rats were lower than those of control rats. MWT and TWL in T2DM rats treated with nano emodin were higher compared with those in T2DM rats. Expression levels of P2X3 protein and messenger RNA (mRNA) in the DRG of T2DM rats were higher than those of controls, while levels in T2DM rats treated with nano emodin were significantly lower than those of the T2DM rats. Phosphorylation and activation of ERK1/2 in the T2DM DRG were decreased by nano emodin treatment. Nano emodin significantly inhibited currents activated by the P2X3 agonist α,β-meATP in HEK293 cells transfected with the P2X3 receptor. Therefore, nano emodin treatment may relieve DNP by decreasing excitatory transmission mediated by the DRG P2X3 receptor in T2DM rats.

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Abbreviations

DPN:

Diabetic peripheral neuropathy

T2DM:

Type 2 diabetes mellitus

α,β-meATP:

α,β-Methyleneadenosine 5′-triphosphate

DRG:

Dorsal root ganglia

MWT:

Mechanical withdrawal threshold

TWL:

Thermal withdrawal latency

Nano emodin:

Nanoparticle-encapsulated emodin

IOD:

Integrated optical density

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Funding information

These studies was supported by grants (Nos.: 81570735, 31560276, 81560219, 81171184, 31060139, 81360136, 81360140, 81560529, and 81200853) from the National Natural Science Foundation of China, a grant (Nos.: 20151BBG70250 and 20151BBG70253) from the Technology Pedestal and Society Development Project of Jiangxi Province, a grant (2014-47) from Major Disciplines of Academic and Technical Leaders Project of Jiangxi Province, a grant (No.: 20142BAB205028, 20171BAB205025, and 20142BAB215027) from the Natural Science Foundation of Jiangxi Province, and grants (Nos.: GJJ13155 and GJJ14319) from the Educational Department of Jiangxi Province.

Author information

Correspondence to Shangdong Liang.

Ethics declarations

The procedures were approved by the Animal Care and Use Committee of Nanchang University Medical School.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Cite this article

Li, L., Sheng, X., Zhao, S. et al. Nanoparticle-encapsulated emodin decreases diabetic neuropathic pain probably via a mechanism involving P2X3 receptor in the dorsal root ganglia. Purinergic Signalling 13, 559–568 (2017). https://doi.org/10.1007/s11302-017-9583-2

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Keywords

  • P2X3 receptor
  • Diabetic peripheral neuropathy
  • Dorsal root ganglia
  • Nanoparticle-encapsulated emodin