Impact of Streptozotocin-Induced Diabetes on Experimental Trigeminal Neuralgia: Analgesic Effect of Cannabidiol

• Grant number: 25/00854-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2025
• End date: February 28, 2027
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Glauce Crivelaro Do Nascimento
• Grantee: Milena Barbosa Costa
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Diabetic neuropathy is a common and debilitating complication of type 1 diabetes, causing chronic pain and impairing patients' quality of life, even with glycemic control. It can also impact the function of the trigeminal nerve, altering orofacial sensory transduction and the perception of orofacial pain. Current treatment for peripheral neuropathic pain, including opioid analgesics and anticonvulsants, is often ineffective and associated with adverse effects. Thus, there is an urgent need to explore therapeutic alternatives that can relieve pain and reverse neuronal degeneration associated with the condition. Cannabidiol (CBD), due to its anti-inflammatory, analgesic, and neuroprotective effects, emerges as a promising option. Studies indicate that experimental models of type 1 diabetes induced by streptozotocin (STZ) in rodents exhibit hyperalgesia in various regions, including the orofacial area, but little is known about the mechanisms involved in the trigeminal circuit. This project aims to investigate the therapeutic potential of CBD in the treatment of neuropathic pain associated with diabetes in male and female Wistar Hannover rats, with a focus on orofacial complications, offering a promising perspective for improving the clinical management of these conditions. Specifically, our objectives are: (i) to assess the presence of orofacial allodynia and hyperalgesia in an experimental diabetes model; (ii) to compare these responses in males and females; (iii) to investigate the impact of experimental diabetes on hyperalgesia and allodynia responses in established trigeminal neuralgia in males and females; (iv) to analyze the effect of CBD, at doses of 3, 10, and 30 mg/kg, on orofacial allodynia and hyperalgesia in rodents subjected to the experimental diabetes model, either alone or associated with trigeminal neuralgia; (v) to evaluate the impact of CBD on pro-inflammatory cytokines and oxidative stress in the trigeminal ganglion and spinal trigeminal nucleus of rodents subjected to experimental diabetes induction, either alone or associated with trigeminal neuralgia. Investigating CBD's properties may open new therapeutic possibilities for the clinical management of these interrelated conditions, contributing to improving the quality of life for diabetic patients. (AU)