lncRNA NONRATT021972 siRNA Decreases Diabetic Neuropathic Pain Mediated by the P2X3 Receptor in Dorsal Root Ganglia

Mol Neurobiol. 2017 Jan;54(1):511-523. doi: 10.1007/s12035-015-9632-1. Epub 2016 Jan 7.

Abstract

Long noncoding RNAs (lncRNAs) participate in physiological and pathophysiological processes. Type 2 diabetes mellitus (T2DM) accounts for more than 90 % of all cases of diabetes mellitus (DM). Diabetic neuropathic pain (DNP) is a common complication of T2DM. The aim of this study was to investigate the effects of lncRNA NONRATT021972 small interference RNA (siRNA) on DNP mediated by the P2X3 receptor in dorsal root ganglia (DRG). These experiments showed that the expression levels of NONRATT021972 in DRG were increased in the T2DM rat model (intraperitoneal injection of STZ with 30 mg/kg). The concentration of NONRATT021972 in T2DM patient serum was higher compared to control healthy subjects. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in T2DM rats were lower compared to control rats. MWT and TWL in T2DM rats treated with NONRATT021972 siRNA were higher compared with those in T2DM rats. The expression levels of the P2X3 protein and messenger RNA (mRNA) of T2DM rat DRG were higher compared to the control, while those in T2DM rats treated with NONRATT021972 siRNA were significantly lower compared to T2DM rats. The level of tumor necrosis factor-α (TNF-α) in the serum of T2DM rats treated with NONRATT021972 siRNA was significantly decreased compared with T2DM rats. NONRATT021972 siRNA inhibited the phosphorylation and activation of ERK1/2 in T2DM DRG. Thus, NONRATT021972 siRNA treatment may suppress the upregulated expression and activation of the P2X3 receptor and reduce the hyperalgesia potentiated by the pro-inflammatory cytokine TNF-α in T2DM rats.

Keywords: Diabetic neuropathic pain; Dorsal root ganglia; Long noncoding RNA; P2X3 receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Neuropathies / drug therapy
  • Diabetic Neuropathies / metabolism*
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism*
  • Humans
  • Male
  • Neuralgia / drug therapy
  • Neuralgia / metabolism*
  • RNA, Long Noncoding / administration & dosage
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2X3 / physiology*

Substances

  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Receptors, Purinergic P2X3
  • long non-coding RNA NONRATT021972, rat