Cannabidiol and Temporomandibular Pain: Peripheral and Central Inflammatory Modulation in a Preclinical Model

• Grant number: 25/00731-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Glauce Crivelaro Do Nascimento
• Grantee: Tayllor Philipe Graciano Silva
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Temporomandibular dysfunction (TMD) is a pathological condition of multifactorial etiology and one of the main causes of non-odontogenic orofacial pain. Developing new therapeutic options for TMD is essential to improve clinical management, reduce pain, and minimize the functional and emotional impacts characteristic of these patients, as well as to expand knowledge about the underlying mechanisms of this condition. Cannabidiol (CBD) has emerged as a compound of significant therapeutic interest due to its analgesic, anti-inflammatory, anticonvulsant, anxiolytic, antidepressant, and antipsychotic properties. Studies have shown its efficacy in managing neuropathic and inflammatory pain, offering significant relief without the psychoactive effects associated with tetrahydrocannabinol (THC). Despite its therapeutic potential, the application of CBD in treating TMD remains underexplored. The hypothesis of this study is that systemic and repeated administration of CBD reduces nociception induced by complete Freund's adjuvant (CFA) injection in the temporomandibular joints (TMJs) of rats. This effect would be mediated by the reduction of local inflammatory mediators and the attenuation of neuroinflammatory processes in peripheral and central nociceptive pathways. The primary objective of this study is to investigate the antinociceptive effect of CBD (i.p., at doses of 1, 3, and 10 mg/kg) on mechanical allodynia induced by CFA injection in the TMJs of male Wistar Hannover rats (200-250g). To achieve this, the study aims to: (i) Evaluate the effect of CBD on mechanical allodynia induced by temporomandibular inflammation using the von Frey test; (ii) Examine the local and peripheral inflammatory profile by assessing pro-inflammatory cytokines (IL-6, IL-1¿, TNF-¿, IFN-¿) and the anti-inflammatory cytokine (IL-10) in the TMJ and trigeminal ganglion after 14 days of CFA injection, investigating CBD's potential anti-inflammatory effect; (iii) Investigate glial cell activation in central pathways by analyzing the expression of microglia and astrocytes in the spinal trigeminal nucleus (Sp5c) after 14 days of CFA-induced inflammation, focusing on CBD's effect on these cells. This study seeks to contribute to the understanding of the mechanisms involved in the modulation of orofacial pain through CBD administration, providing a foundation for developing new therapeutic approaches in TMD management