The Role of NF-κB/NLRP3 Inflammasome Signaling Pathway in Attenuating Pyroptosis by Melatonin Upon Spinal Nerve Ligation Models

Accumulated evidence has demonstrated causative links between neuropathic pain (NP) and immune-mediated inflammatory disorders. However, the role of inflammasome-induced pyroptosis in NP remains elusive. Melatonin possesses a well-documented analgesic action in various pain models. The current study...

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Veröffentlicht in:Neurochemical research 2022-02, Vol.47 (2), p.335-346
Hauptverfasser: Wang, Yi-Hao, Gao, Xiao, Tang, Yu-Ru, Yu, Yang, Sun, Ming-jie, Chen, Fu-qiang, Li, Yan
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container_issue 2
container_start_page 335
container_title Neurochemical research
container_volume 47
creator Wang, Yi-Hao
Gao, Xiao
Tang, Yu-Ru
Yu, Yang
Sun, Ming-jie
Chen, Fu-qiang
Li, Yan
description Accumulated evidence has demonstrated causative links between neuropathic pain (NP) and immune-mediated inflammatory disorders. However, the role of inflammasome-induced pyroptosis in NP remains elusive. Melatonin possesses a well-documented analgesic action in various pain models. The current study aimed to test our hypothesis that melatonin regulated pyroptosis to alleviate NP by inhibiting NF-κB/NLRP3-dependent signaling. A rat model of spinal nerve ligation (SNL) was established to explore the potential association between melatonin and pyroptosis. Behavioral experiments revealed that SNL provoked severe allodynia which was suppressed by the administration of melatonin, a caspase-1 inhibitor (VX-765), or an NF-κB inhibitor (BAY 11-7085). SNL significantly up-regulated the inflammatory cytokines associated with the excessive activation of NLRP3 components and NF-κB signaling, as well as a marked pyroptosis activation. These effects were partially inhibited by melatonin, VX-765 or BAY 11-7085, and when melatonin and inhibitors were added together, the effect was enhanced. In conclusion, melatonin has potent analgesic and anti-inflammatory effects in SNL models through preventing pyroptosis via the NF-κB/NLRP3 inflammasome signaling pathway.
doi_str_mv 10.1007/s11064-021-03450-7
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subjects Analgesics
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
Caspase-1
Cell Biology
Cytokines
Inflammasomes
Inflammasomes - metabolism
Inflammatory diseases
Inhibitors
Melatonin
Melatonin - pharmacology
Melatonin - therapeutic use
Neuralgia
Neurochemistry
Neurology
Neurosciences
NF-kappa B - metabolism
NF-κB protein
NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
Original Paper
Pain
Pain perception
Pyroptosis
Rats
Signal Transduction
Signaling
Spinal nerves
Spinal Nerves - metabolism
title The Role of NF-κB/NLRP3 Inflammasome Signaling Pathway in Attenuating Pyroptosis by Melatonin Upon Spinal Nerve Ligation Models
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