Open Access<p>Spinal TLR4/P2X7 Receptor-Dependent NLRP3 Inflammasome Activation Contributes to the Development of Tolerance to Morphine-Induced Antinociception</p>
Author(s) -
Haiyan Wang,
Yu Zhang,
Xiaqing Ma,
Wenying Wang,
Xiaojun Xu,
Min Huang,
Liang Xu,
Haibo Shi,
TiFei Yuan,
Wei Jiang,
Aizhong Wang,
Tan Xu
Publication year - 2020
Publication title -
journal of inflammation research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.656
H-Index - 33
ISSN - 1178-7031
DOI - 10.2147/jir.s266995
Subject(s) - inflammasome , tlr4 , microglia , neuroinflammation , morphine , pharmacology , downregulation and upregulation , nociception , knockout mouse , receptor , drug tolerance , medicine , chemistry , immunology , inflammation , biochemistry , gene
Long-term use of morphine induces antinociceptive tolerance and limits its clinical efficacy. Neuroinflammation in the spinal cord is thought to play a pivotal role in the development of morphine tolerance. Toll-like receptor 4 (TLR4) and P2X7 receptor (P2X7R) are key modulators of neuroinflammation. Recent studies show that the Nod-like receptor protein 3 (NLRP3) inflammasome play a crucial role in microglia-mediated neuroinflammation. Thus far, the mechanism underlying NLRP3 inflammasome activation during morphine-induced tolerance is not yet fully understood. Therefore, we sought to investigate the mechanisms of NLRP3 inflammasome activation and its role in the development of morphine-induced tolerance.