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Melatonin Attenuates Pyroptosis Upon Spinal Nerve Ligation in Rats via the NF-κB/NLRP3 Inflammasome Signaling Pathway
Yan Li
The Affiliated Hospital of Qingdao University
Corresponding Author
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Accumulated evidences have 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. A rat model of spinal nerve ligation was established to explore the potential mechanism of melatonin in pyroptosis. The current study aimed to test our hypothesis that melatonin regulated pyroptosis to alleviate NP by inhibiting NF-κB/NLRP3-dependent signaling. Behavioral experiments revealed that SNL provoked severe allodynia which were suppressed by the administration of melatonin, caspase-1 inhibitor (VX-765) or 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 the marked pyroptosis activation which were partially inhibited by melatonin, VX-765 or BAY 11-7085. Collectively, Melatonin has potent analgesic and anti-inflammatory effects in SNL models through preventing pyroptosis via the NF-κB/NLRP3 inflammasome signaling pathway.
Keywords
melatonin, NLRP3 inflammasome, pyroptosis, spinal nerve ligation, neuropathic pain, NF-κB
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On 15 Feb, 2021
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Received 15 Feb, 2021
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Received 15 Feb, 2021
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This preprint is under consideration at Journal of Translational Medicine. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Melatonin Attenuates Pyroptosis Upon Spinal Nerve Ligation in Rats via the NF-κB/NLRP3 Inflammasome Signaling Pathway
Yan Li
The Affiliated Hospital of Qingdao University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 22 Feb, 2021
No community comments so far
Reviewer #4 agreed
On 24 Feb, 2021
Reviewer #3 agreed
On 20 Feb, 2021
Reviewer #2 agreed
On 20 Feb, 2021
Reviewer #1 agreed
On 15 Feb, 2021
Review #1 received
Received 15 Feb, 2021
Review #? received
Received 15 Feb, 2021
Reviewers invited
Invitations sent on 15 Feb, 2021
Editor assigned
On 09 Feb, 2021
Submission checks complete
On 09 Feb, 2021
Editor invited
On 09 Feb, 2021
First submitted
On 07 Feb, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Translational Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Accumulated evidences have 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. A rat model of spinal nerve ligation was established to explore the potential mechanism of melatonin in pyroptosis. The current study aimed to test our hypothesis that melatonin regulated pyroptosis to alleviate NP by inhibiting NF-κB/NLRP3-dependent signaling. Behavioral experiments revealed that SNL provoked severe allodynia which were suppressed by the administration of melatonin, caspase-1 inhibitor (VX-765) or 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 the marked pyroptosis activation which were partially inhibited by melatonin, VX-765 or BAY 11-7085. Collectively, Melatonin has potent analgesic and anti-inflammatory effects in SNL models through preventing pyroptosis via the NF-κB/NLRP3 inflammasome signaling pathway.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6