Dietary supplementation with grape seed extract prevents development of trigeminal sensitization and inhibits pain signaling in a preclinical chronic temporomandibular disorder model


Background: The risk factors neck muscle tension, prolonged jaw opening, and female gender are associated with developing temporomandibular disorders (TMD), which are characterized by persistent sensitization of trigeminal neurons and enhanced pain signaling. Dietary supplementation with a grape seed extract (GSE) can modulate expression of proteins that decrease neuronal excitability and trigeminal sensitization.

Methods: Mechanical nocifensive thresholds over the masseter were determined using von Frey filaments in male and female adult Sprague Dawley rats. To promote trigeminal sensitization, animals were injected with complete Freund’s adjuvant in the upper trapezius. After 8 days, animals were subjected to near maximal jaw opening and head withdrawal responses were determined for 28 days. Some animals received continuous supplementation with 0.5% GSE in their drinking water two weeks prior to trapezius injections.

Results: Prolonged jaw opening increased the average number of nocifensive responses to mechanical stimuli for 14 days in males and females. However, trapezius inflammation prior to jaw opening promoted persistent mechanical sensitivity up to 28 days post-jaw opening in females, while in males nociceptive levels were still elevated at day 21. Supplementation with GSE, which is enriched in polyphenols and exhibits antioxidant and COX-2 activity, inhibited trigeminal nociception in response to jaw opening in both male and female sensitized animals.

Conclusions: Our findings provide evidence that multiple risk factors contribute to the development of a prolonged state of trigeminal sensitization that is more severe in females and provide preclinical evidence that supplementation with GSE could be beneficial in the management of TMD.


JVIC-Center for Biological and Life Sciences

Document Type




masseter, pain, sensitization, trapezius, trigeminal

Publication Date


Journal Title

Journal of Oral Pathology and Medicine