ArticleNeurochemical research2023
Toll-like Receptor 2-Melatonin Feedback Loop Regulates the Activation of Spinal NLRP3 Inflammasome in Morphine-Tolerant Rats.
Article in Neurochemical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 7 citations in OpenAlex.
- The therapeutic potential of phytochemicals in morphine tolerance: targeting microglia-mediated neuroinflammation.Frontiers in pharmacology · 2025Review
- C3/C3aR Bridges Spinal Astrocyte-Microglia Crosstalk and Accelerates Neuroinflammation in Morphine-Tolerant Rats.CNS neuroscience & therapeutics · 2025Article
- Microglia in morphine tolerance: cellular and molecular mechanisms and therapeutic potential.Frontiers in pharmacology · 2024Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
background and purposeMorphine is amongst the most effective analgesics available for the management of severe pain. However, prolonged morphine treatment leads to analgesic tolerance which limits its clinical usage. Previous studies have demonstrated that melatonin ameliorates morphine tolerance by reducing neuroinflammation. However, little is known about the relationship between Toll like receptor 2 (TLR2) and neuroinflammation in morphine tolerance. The aim of this study was to explore the role of TLR2 in morphine tolerance and its connections with melatonin and Nod-like receptor protein 3 (NLRP3) inflammasome.
methodsSprague-Dawley rats were treated with morphine for 7 days and tail-flick latency test was performed to identify the induction of analgesic tolerance. The roles of TLR2 in microglia activation and morphine tolerance were assessed pharmacologically, and the possible interactions between melatonin, TLR2 and NLRP3 inflammasome were investigated. KEY
resultsMorphine tolerance was accompanied by increased TLR2 expression and NLRP3 inflammasome activation in spinal cord. whereas melatonin level was down-regulated. Chronic melatonin administration resulted in a reduced TLR2 expression and NLRP3 inflammasome activation. Moreover, the analgesic effect of morphine was partially restored. Inhibition of TLR2 suppressed the microglia and NLRP3 inflammasome activation, as well as restored the spinal melatonin level while attenuated the development of morphine tolerance. Furthermore, the inhibition of microglia activation ameliorated morphine tolerance via inhibiting TLR2-NLRP3 inflammasome signaling in spinal cord.
conclusionIn this study, we directly demonstrate a TLR2-melatonin negative feedback loop regulating microglia and NLRP3 inflammasome activation during the development of morphine tolerance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.