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Toll-Like Receptor 4 in the Rat Caudal Medulla Mediates Tooth Pulp Inflammatory Pain
Helena F Filippini1,2, Graziella R Molska2, Maryam Zanjir2
1Programa de Pós-graduação em Odontologia, Escola de Ciência da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
Abstract:
The aims of this study were to investigate if Toll-like receptor 4 (TLR4) is expressed in the medullary dorsal horn (MDH) and if medullary application of a TLR4 antagonist (lipopolysaccharides from Rhodobacter sphaeroides, LPS-RS) can attenuate changes in nociceptive sensorimotor responses or TLR4 expression that might be evoked by mustard oil (MO) application to the right maxillary first molar tooth pulp. Of 41 adult male Sprague-Dawley rats used in the study, 23 received intrathecal application of the TLR4 antagonist LPS-RS (25 μg/10 μl; LPS-RS group) or isotonic saline (10 μl; vehicle control group) 10 min before pulpal application of MO (95%; 0.2 μl). Bilateral electromyographic (EMG) activities of the anterior digastric and masseter muscles were recorded continuously before and until 15 min after the MO application to the pulp. In 6 of these 23 rats and an additional 18 rats, the caudal medulla containing the ipsilateral and contralateral MDH was removed after euthanasia for subsequent Western Blot analysis of TLR4 expression in LPS-RS (n = 8) and vehicle (n = 8) groups and a naïve group (n = 8). The % change from baseline in the MO-evoked EMG activities within the anterior digastric muscles were significantly smaller in the LPS-RS group than the control group (two-way ANOVA, post hoc Bonferroni, P < 0.0001). Western Blot analysis revealed similar levels of TLR4 expression in the caudal medulla of the naïve, vehicle and LPS-RS groups. These novel findings suggest that TLR4 signaling in the caudal medulla may mediate MO-induced acute dental inflammatory pain in rats.
Insights
Toll-like receptor 4 (TLR4) signaling in the rat caudal medulla plays a role in acute dental pain. Blocking TLR4 with an antagonist reduced pain responses evoked by mustard oil, suggesting a therapeutic target.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Dental pain, particularly inflammatory pain, significantly impacts quality of life.
- Toll-like receptor 4 (TLR4) is implicated in various pain pathways, but its role in dental pain is not fully understood.
- The medullary dorsal horn (MDH) is a key area for processing orofacial pain signals.
Purpose of the Study:
- To determine if TLR4 is expressed in the rat MDH.
- To investigate if blocking TLR4 in the medulla can reduce pain responses to dental pulp stimulation.
- To assess the effect of TLR4 antagonism on TLR4 expression in the MDH.
Main Methods:
- Adult male Sprague-Dawley rats underwent intrathecal administration of a TLR4 antagonist (LPS-RS) or vehicle.
- Mustard oil (MO) was applied to the maxillary first molar pulp to induce pain.
- Electromyographic (EMG) activity of jaw muscles and Western Blot analysis of medullary TLR4 expression were performed.
Main Results:
- Intrathecal LPS-RS significantly attenuated the EMG activity changes evoked by MO application compared to the control group.
- Western Blot analysis showed no significant difference in TLR4 expression levels across naïve, vehicle, and LPS-RS groups.
- These findings indicate TLR4 signaling in the caudal medulla mediates MO-induced acute dental inflammatory pain.
Conclusions:
- TLR4 is expressed in the rat caudal medulla and contributes to acute dental inflammatory pain.
- Medullary application of a TLR4 antagonist effectively reduces pain-related sensorimotor responses.
- Targeting TLR4 signaling in the caudal medulla represents a potential therapeutic strategy for dental pain management.
