METTL3 regulates inflammatory pain by modulating m⁶A-dependent pri-miR-365-3p processing

Area of Science:

• Neuroscience
• Molecular Biology
• Epigenetics

Background:

• RNA N6-methyladenosine (m6A) modification regulates diverse biological processes.
• The role of m6A in nociceptive modulation remains largely unexplored.
• Chronic inflammatory pain is a significant health concern with complex underlying mechanisms.

Purpose of the Study:

• To investigate the role of m6A modification and METTL3 in chronic inflammatory pain.
• To elucidate the molecular mechanisms by which METTL3 influences nociception.
• To explore potential therapeutic targets for pathological pain.

Main Methods:

• Utilized a Complete Freund's Adjuvant (CFA)-induced chronic inflammatory pain mouse model.
• Assessed spinal m6A levels and METTL3 expression.
• Performed knockdown and overexpression of spinal METTL3.
• Investigated pri-miR-65-3p processing in a DiGeorge critical region 8-dependent manner.

Main Results:

• Spinal m6A modification and METTL3 expression were significantly increased in CFA-induced pain.
• Knockdown of spinal METTL3 prevented and reversed pain behaviors and neuronal sensitization.
• Overexpression of spinal METTL3 induced pain behaviors and neuronal sensitization in naive mice.
• METTL3 positively modulated pri-miR-65-3p processing via DiGeorge critical region 8.

Conclusions:

• METTL3-mediated m6A modification plays a crucial role in nociceptive sensitization.
• METTL3 is a key regulator in the development of pathological pain.
• This study offers a novel perspective on m6A modification in pain pathways.