Role of GABAergic and glutamatergic neurotransmission in the analgesic effect of cannabinoid compounds in trigeminal neuralgia.

• Grant number: 24/07049-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2024
• End date: September 30, 2027
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Glauce Crivelaro Do Nascimento
• Grantee: Daniela Escobar
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Trigeminal neuralgia (TN) is a chronic and debilitating condition characterized by intense pain following injury or inflammation of the peripheral trigeminal nerve. Symptoms include hyperalgesia and mechanical and thermal allodynia. The pathophysiology involves structural and functional changes both at the peripheral and central levels, affecting the modulation of central pathways with increased excitatory neurotransmission, such as glutamatergic, and decreased inhibitory neurotransmission, such as GABAergic. Traditional treatment with anticonvulsants has efficacy limitations and may cause significant side effects, making TN a therapeutic challenge. Non-psychotomimetic cannabinoids emerge as a promising alternative in the management of trigeminal neuropathic pain.This study investigates the potential effect of cannabinoids (Cannabidiol, Cannabigerol, and Full Spectrum) at different doses (3, 10, 30mg/kg, administered intraperitoneally) on the overall expression of RNAs involved in the modulation of glutamatergic and GABAergic signaling in a rat model of trigeminal neuralgia induced by infraorbital nerve constriction (IoN-CCI). The main objectives are: (i) To evaluate the effect of cannabinoid therapies on orofacial mechanical allodynia and thermal hyperalgesia in male and female rats; (ii) To analyze the excitatory/inhibitory balance through the expression of proteins related to glutamatergic and GABAergic neurotransmission (GLUT-GABA); (iii) To investigate the expression of these proteins in neurons and glial cells; (iv) To characterize the gene expression profile of mRNAs and ncRNAs (microRNAs and piRNAs) involved in the regulation of receptors and transporters of the GLUT-GABA system in the trigeminal ganglion and the caudal subnucleus of the trigeminal spinal nucleus. It is expected that the results of this study will contribute to a better understanding of trigeminal neurophysiology and provide valuable insights for the development of more effective treatments and the identification of new therapeutic targets for trigeminal neuralgia.