Influence of TRPV1 on Thermal Nociception in Rats with Temporomandibular Joint Persistent Inflammation Evaluated by the Operant Orofacial Pain Assessment Device (OPAD)

Abstract

Background

Temporomandibular joint (TMJ)-associated inflammation contributes to the pain reported by patients with temporomandibular disorders (TMD). It is common for patients diagnosed with TMD to report pain in the masticatory muscles and temporomandibular joints, headache, and jaw movement disturbances. Although TMD can have different origins, including trauma and malocclusion disorder, anxiety/depression substantially impacts the development and maintenance of TMD. In general, rodent studies on orofacial pain mechanisms involve the use of tests originally developed for other body regions, which were adapted to the orofacial area. To overcome limitations and expand knowledge in orofacial pain, our group validated and characterized an operant assessment paradigm in rats with both hot and cold stimuli as well mechanical stimuli. Nevertheless, persistent inflammation of the TMJ has not been evaluated with this operant orofacial pain assessment device (OPAD).

Methods

We characterized the thermal orofacial sensitivity for cold, neutral, and hot stimuli during the development of TMD using the OPAD behavior test. In addition, we evaluated the role of transient receptor potential vanilloid 1 (TRPV1) expressing nociceptors in rats with persistent TMJ inflammation. The experiments were performed in male and female rats with TMJ inflammation induced by carrageenan (CARR). Additionally, resiniferatoxin (RTX) was administered into the TMJs prior CARR to lesion TRPV1-expressing neurons to evaluate the role of TRPV1-expressing neurons.

Results

We evidenced an increase in the number of facial contacts and changes in the number of reward licks per stimulus on neutral (37°C) and cold (21°C) temperatures. However, at the hot temperature (42°C), the inflammation did not induce changes in the OPAD test. The prior administration of RTX in the TMJ prevented the allodynia and thermal hyperalgesia induced by CARR.

Conclusion

We showed that TRPV-expressing neurons are involved in the sensitivity to carrageenan-induced pain in male and female rats evaluated in the OPAD.

Keywords:

• temporomandibular disorder
• acute pain
• TRPV1
• operant assay
• orofacial pain

Abbreviations

5-HT, 5-hydroxytryptamine; ATP, adenosine triphosphate; CARR, carrageenan; CFA, Complete Freund’s adjuvant; GABA, gamma aminobutyric acid; L/F, lick/face ratio; OPAD, operant orofacial pain assessment device; PAG, periaqueductal gray; RTX, resiniferatoxin; TMD, temporomandibular disorder; TMJ, temporomandibular joint; TRPV1, transient receptor potential vanilloid 1.

Data Sharing Statement

The raw data supporting the development of this article can be directed to the corresponding author.

Ethics Statement

The animal study was reviewed and approved by the Association for Assessment and Accreditation of Laboratory Animal Care and with approval by the University of Florida’s Institutional Animal Care and Use Committee.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Funding

CRALP was granted a research fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil (FAPESP grant number #2014/15891-0), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq grants number #309215/2019-6, #306424/2022-3).