Curcumin ameliorates neuropathic pain by down-regulating spinal IL-1β via suppressing astroglial NALP1 inflammasome and JAK2-STAT3 signalling

Sci Rep. 2016 Jul 6;6:28956. doi: 10.1038/srep28956.

Abstract

Curcumin has been shown to possess strong anti-inflammatory activity in many diseases. It has been demonstrated that the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) cascade and the NAcht leucine-rich-repeat protein 1 (NALP1) inflammasome are important for the synthesis of Pro-Interleukin (IL)-1β and the processing of the inactive protein to its mature form, which plays an active role in the pathogenesis of neuropathic pain. The present study showed that repeated intraperitoneal injection of curcumin ameliorated SNI-induced mechanical and cold allodynia in a dose-dependent manner and inhibited the elevation of spinal mature IL-1β protein levels. Additionally, repeated curcumin treatment significantly inhibited the aggregation of the NALP1 inflammasome and the activation of the JAK2-STAT3 cascade in spinal astrocytes. Furthermore, the genetic down-regulation of NALP1 inflammasome activation by NALP1 siRNA and the pharmacological inhibition of the JAK2-STAT3 cascade by AG490 markedly inhibited IL-1β maturation and Pro-IL-1β synthesis, respectively, and reduced SNI-induced pain hypersensitivity. Our results suggest that curcumin attenuated neuropathic pain and down-regulated the production of spinal mature IL-1β by inhibiting the aggregation of NALP1 inflammasome and the activation of the JAK2-STAT3 cascade in astrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Curcumin / pharmacology*
  • Down-Regulation / drug effects*
  • Hyperalgesia / metabolism
  • Inflammasomes / metabolism
  • Interleukin-1beta / metabolism*
  • Janus Kinase 2 / metabolism*
  • Male
  • Mice, Inbred BALB C
  • Neuralgia / drug therapy*
  • Neuralgia / metabolism
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • IL1B protein, mouse
  • Inflammasomes
  • Interleukin-1beta
  • NALP1 protein, mouse
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Jak2 protein, mouse
  • Janus Kinase 2
  • Curcumin