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Exogenous melatonin alleviates neuropathic pain-induced affective disorders by suppressing NF-κB/ NLRP3 pathway and

Tahmineh Mokhtari1,2, Lu-Peng Yue3,4, Li Hu5,6

  • 1CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China.

Scientific Reports
|February 7, 2023
PubMed

Insights

Melatonin (MLT) alleviates neuropathic pain (NP)-induced anxiety and depression in rats by reducing inflammation and apoptosis. MLT treatment improved behaviors and modulated key molecular pathways in the brain.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Neuropathic pain (NP) is often accompanied by affective disorders like anxiety and depression.
  • The underlying mechanisms involve neuroinflammation and apoptosis, particularly in the prefrontal cortex (PFC) and hippocampus (HC).

Purpose of the Study:

  • To investigate the anti-inflammatory and anti-apoptotic effects of melatonin (MLT) on neuropathic pain (NP)-induced anxiety and depression in a rat model.
  • To explore the molecular mechanisms, including the NF-κB/NLRP3 inflammasome pathway and apoptosis-related proteins, modulated by MLT.

Main Methods:

  • Adult male rats underwent chronic constrictive injury (CCI) to induce NP.
  • Rats were treated with either vehicle or melatonin (10 mg/kg).
  • Behavioral tests, molecular analyses (NF-κB, NLRP3, cytokines, Bax, Bcl2), and histopathology were performed on PFC and HC tissues.

Main Results:

  • NP induced significant anxiety- and depressive-like behaviors in rats.
  • NP activated the NF-κB/NLRP3 inflammasome pathway and increased pro-inflammatory cytokines (IL-1β, IL-18) in the PFC and HC.
  • NP led to increased cell apoptosis by upregulating Bax and downregulating Bcl2.
  • Melatonin treatment reversed these NP-induced effects, reducing pain, anxiety, and depression, and ameliorating neuroinflammation and apoptosis.

Conclusions:

  • Melatonin exhibits significant anti-inflammatory and anti-apoptotic properties.
  • These properties mediate the beneficial effects of MLT in alleviating affective disorders associated with neuropathic pain.
  • MLT modulates the NF-κB/NLRP3 inflammasome pathway and apoptosis-related proteins, offering a potential therapeutic strategy for NP-related mental health issues.

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