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

International Journal of Molecular Sciences

Marika Cordaro¹  Roberta Fusco²  Rosalba Siracusa²  Andrea Maria Sforza²  Livia Interdonato²  Rosanna Di Paola²  Alessio Filippo Peritore²  Salvatore Cuzzocrea²  Ramona D’Amico²  Daniela Impellizzeri²  Tiziana Genovese²  Rosalia Crupi³  Enrico Gugliandolo³ 

[1] Department of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, via Consolare Valeria, 98125 Messina, Italy;Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy;Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy;

关键词: fibromyalgia;    P2X7 receptor;    NLRP3 inflammasome;    neuroinflammation;   

DOI  :  10.3390/ijms22126471

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown