Involvement of Transient Receptor Potential Channels in the Antinociceptive Effect of Cannabidiol on Trigeminal Pain: sex-dependent effect?lgia Syndrome

• Grant number: 24/07791-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: November 30, 2025
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Glauce Crivelaro Do Nascimento
• Grantee: Gabriela Gonçalves Bálico
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Trigeminal neuralgia (TN) is a condition characterized by intense and disabling orofacial pain. The pathophysiology of neuropathic pain is multifaceted, involving functional changes in both the central nervous system (CNS) and the peripheral nervous system (PNS), along with neuroimmune interactions. The hypersensitivity of these systems results in the manifestation of responses such as thermal allodynia, mechanical allodynia, and hyperalgesia. It is relevant to note that the higher incidence of neuropathies in women compared to men highlights sex as a crucial factor in understanding the mechanisms associated with this disease. Furthermore, the response to analgesic therapy, whether through drugs, somatic manipulations, or situational adjustments, is also related to the patient's sex. Although carbamazepine is considered the gold standard treatment for TN, providing pain relief, it is associated with various side effects. Therefore, effective management of TN remains a significant therapeutic challenge. In this study, we will investigate the antinociceptive effect of cannabidiol (CBD), PECS-101 (a synthetic cannabinoid, formerly known as HUF-101), and carbamazepine over 7 days, at doses of 3, 10, and 30 mg/kg, in male and female subjects undergoing the TN model. Additionally, we will examine the role of transient receptor potential vanilloid type 1 (TRPV1) receptor, which plays a fundamental role in the development of painful sensation and is present in the trigeminal ganglion. For this purpose, male and female Wistar Hannover rats (weighing between 150-200g) will undergo unilateral (right side) infraorbital nerve injury through chronic constriction (IoN-CCI). The antinociceptive effect will be assessed using Von Frey and Formalin tests, while motor coordination will be analyzed through the Rota-Rod test. TRPV1 expression will be evaluated using Western Blotting technique in the trigeminal ganglion.