BoNT Injection into Temporomandibular Joint Alleviates TMJ Pain in Forced Mouth Opening Mouse Model

Area of Science:

• Neuroscience
• Pain Management
• Molecular Biology

Background:

• Temporomandibular disorder (TMD) causes chronic pain and limited jaw function, significantly impacting patient quality of life.
• Current TMD treatments, including pharmacologic, physical, and surgical options, offer limited effectiveness.
• Botulinum toxin (BoNT) is explored as a novel therapeutic for TMD due to its known effects on muscle and nerve activity.

Purpose of the Study:

• To investigate the efficacy of botulinum toxin (BoNT) as a therapeutic agent for temporomandibular disorder (TMD).
• To elucidate the underlying mechanisms by which BoNT alleviates TMD-associated pain and dysfunction.
• To evaluate BoNT's impact on neural activity and pain-related protein expression in a mouse model of TMD.

Main Methods:

• Developed a forced mouth opening (FMO)-induced TMD mouse model.
• Administered BoNT and assessed pain behaviors using von Frey and mouse grimace tests.
• Evaluated motor function and feeding with open field and pasta gnawing tests.
• Monitored trigeminal ganglia (TG) neural activity using in vivo calcium imaging.
• Quantified expression of pain-related proteins (TRPV1, TRPA1, TRPC1) and VGLUT2 via Western blot or similar techniques.

Main Results:

• BoNT injection significantly reduced mechanical hypersensitivity and pain behaviors in the TMD mouse model.
• BoNT improved motor function and food intake without causing general behavioral impairments.
• In vivo imaging showed BoNT suppressed both spontaneous and stimulus-evoked activity in TG neurons.
• BoNT downregulated the expression of pain-promoting proteins (TRPV1, TRPA1, TRPC1) and VGLUT2 in the TG.

Conclusions:

• Botulinum toxin (BoNT) is a promising therapeutic agent for alleviating pain and dysfunction associated with temporomandibular disorders (TMD).
• BoNT exerts its therapeutic effects by suppressing peripheral neural activity in the trigeminal ganglia (TG) and downregulating key pain-related proteins.
• This study provides a novel mechanistic understanding of BoNT's action in TMD and supports its potential for long-lasting TMJ pain management.