Inhibition of P2X7 Purinergic Receptor Ameliorates Fibromyalgia Syndrome by Suppressing NLRP3 Pathway

Int J Mol Sci. 2021 Jun 16;22(12):6471. doi: 10.3390/ijms22126471.

Abstract

Fibromyalgia is a chronic condition characterized by persistent widespread pain that significantly reduces quality of life in patients. The purinergic P2X7 receptor (P2X7R) seems to be involved in different pain states and neuroinflammation. The purpose of this study is to investigate the positive effects of P2X7R inhibition by the antagonist Brilliant Blue G (BBG) in a rat model of reserpine-induced fibromyalgia. Sprague-Dawley male rats were injected with 1 mg/kg of reserpine for three consecutive days. Later, animals were administered BBG (50 mg/kg) intraperitoneally for seven days. Reserpine injections induced a significant increase in pain pro-inflammatory mediators as well as a significant increase in neuroinflammation. Chronic pain, in turn, led to depressive-like symptoms and reduced neurogenesis. Blockage of P2X7R by BBG administrations is able to attenuate the behavioral deficits, pain mediators and microglial activation induced by reserpine injection. Additionally, BBG prevents NLRP3 inflammasome activation and consequently the release of active interleukin (IL)-1 and IL-18, involved in the activation of nociceptors. In conclusion, these results suggest that inhibition of P2X7R should be further investigated to develop a potential approach for the management of fibromyalgia.

Keywords: NLRP3 inflammasome; P2X7 receptor; fibromyalgia; neuroinflammation.

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • Cell Degranulation / drug effects
  • Disease Management
  • Disease Models, Animal
  • Fibromyalgia / drug therapy
  • Fibromyalgia / etiology
  • Fibromyalgia / metabolism*
  • Inflammasomes / metabolism
  • Mast Cells / drug effects
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Microglia / drug effects
  • Microglia / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Neurogenesis / drug effects
  • Purinergic P2X Receptor Antagonists / pharmacology*
  • Rats
  • Receptors, Purinergic P2X7 / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Purinergic P2X Receptor Antagonists
  • Receptors, Purinergic P2X7