Melatonin Induces Analgesic Effects through MT₂ Receptor-Mediated Neuroimmune Modulation in the Mice Anterior...

Area of Science:

• Neuroscience
• Pharmacology
• Immunology

Background:

• Neuropathic pain (NP) is a debilitating condition with limited therapeutic options.
• Melatonin (MLT), known for its sleep-promoting effects, shows potential analgesic properties.
• The precise mechanisms of MLT's pain-relieving effects, especially in the cortex, are not fully understood.

Purpose of the Study:

• To investigate the efficacy and underlying mechanisms of melatonin in alleviating neuropathic pain.
• To explore the role of the anterior cingulate cortex (ACC) and its specific receptors in MLT's analgesic effects.
• To elucidate the neuroimmune modulation pathways influenced by MLT in the context of chronic pain.

Main Methods:

• A neuropathic pain mouse model was established using spared nerve injury (SNI).
• Melatonin was administered intraperitoneally and directly into the anterior cingulate cortex (ACC).
• Neuropathic pain symptoms, receptor involvement (MT1R, MT2R), neuronal excitability, microglial polarization, and gene expression were analyzed.

Main Results:

• Melatonin significantly alleviated neuropathic pain symptoms in a dose-dependent manner.
• The analgesic effect was selectively mediated by the MT2 receptor (MT2R) in the ACC, not MT1R.
• Melatonin modulated Gα(i) signaling to reduce pyramidal cell excitability and shifted microglia from M1 to M2 phenotype, reducing inflammation.

Conclusions:

• Melatonin exerts neuropathic pain relief through MT2R-mediated neuroimmune modulation in the ACC.
• This pathway involves inhibiting neuronal excitability and promoting anti-inflammatory microglial responses.
• Melatonin presents a promising therapeutic strategy for managing chronic neuropathic pain.