5-HT3/7 and GABAB receptors mediate inhibition of trigeminal nociception by dietary supplementation of grape seed extract

Background: Temporomandibular joint disorder is a prevalent orofacial pain condition involving sensitization and activation of trigeminal nociceptive neurons. Dietary supplementation with a proanthocyanin-enriched grape seed extract (GSE) was found to inhibit trigeminal nociception in a chronic TMD model. In this study, the cellular mechanisms by which GSE inhibits sustained trigeminal nociception in male and female Sprague Dawley rats were investigated.Methods: Some animals were supplemented with 0.5% GSE dissolved in their water one week prior to neck muscle inflammation induced by injection of complete Freund's adjuvant into the trapezius. To investigate the mechanism of GSE, some animals were injected intracisternally with antagonists of 5-HT3, 5-HT7, GABAA, or GABAB, receptor prior to jaw opening.Results: In males and females, trapezius inflammation prior to jaw opening resulted in sustained mechanical hypersensitivity of trigeminal nociceptors that was significantly inhibited by GSE. Further, GSE beginning 14 days post jaw opening also inhibited trigeminal nociception. Intracisternal injection of antagonists of the 5-HT3/7 and GABAB, but not GABAA receptors reduced the anti-nocifensive effect of GSE in both sexes. Neuronal expression of GABAB protein and mRNA in the spinal cord and trigeminal ganglion were detected.Conclusions: The inhibitory effect of GSE is mediated via activation of 5-HT3/7 receptors and GABAB to enhance central descending inhibitory pain pathways and suppress ongoing trigeminal nociception. Further, our findings support the use of GSE as a dietary supplement in the management of pain associated with TMD and other orofacial pain conditions involving central sensitization and dysfunction of descending pain modulation.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:25

Enthalten in:

Nutritional neuroscience - 25(2022), 8 vom: 03. Aug., Seite 1565-1576

Sprache:

Englisch

Beteiligte Personen:

Cornelison, Lauren E [VerfasserIn]
Woodman, Sara E [VerfasserIn]
Durham, Paul L [VerfasserIn]

Links:

Volltext

Themen:

Dietary supplement
GABA
Grape Seed Extract
Grape seed extract
Journal Article
Pain
Receptors, GABA-B
Sensitization
Serotonin
TMD
Trigeminal

Anmerkungen:

Date Completed 01.08.2022

Date Revised 02.08.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1080/1028415X.2021.1880211

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM321046455