Effects of Cannabidiol Associated with Physical Exercise on Trigeminal Neuralgia

• Grant number: 25/07827-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: June 30, 2026
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Glauce Crivelaro Do Nascimento
• Grantee: Thiago Germano dos Santos
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 23/16182-2 - Cannabidiol in the treatment of neuropsychiatric disorders: new paths, AP.TEM

Abstract

Neuropathic pain, resulting from injuries to the central (CNS) or peripheral nervous system, represents a major therapeutic challenge due to its resistance to conventional treatments. Among its most debilitating manifestations, trigeminal nerve neuralgia stands out as a high-intensity and difficult-to-manage condition, characterized by mechanical allodynia, thermal hyperalgesia, and spontaneous pain. The multifactorial etiology of this orofacial neuropathy limits the effectiveness of current pharmacological approaches, requiring the search for innovative therapeutic strategies.Physical exercise is widely recognized for its ability to modulate pain and exert neuroprotective effects, promoted by the release of endorphins and anti-inflammatory mediators. In parallel, cannabidiol (CBD) has emerged as a promising compound in the treatment of neuropathic pain due to its analgesic and anti-inflammatory properties. This study is based on the hypothesis that the combination of CBD and physical exercise enhances analgesia in trigeminal neuralgia. We propose that this effect is related to the modulation of the neuroinflammatory environment in brain regions involved in the processing and descending control of orofacial pain. The aim of this study is to investigate the effect of treatment with CBD (10 mg/kg), either alone or in combination with aerobic physical exercise, on nociception induced by infraorbital nerve constriction-a classic model of trigeminal neuralgia in male Wistar-Hannover rats. Nociceptive response assessment will be performed using the Von Frey test for mechanical allodynia. CBD will be administered intraperitoneally for three days, characterizing a subchronic treatment. In addition to behavioral evaluation, we will analyze the neuroinflammatory mechanisms underlying pain modulation. To this end, we will investigate the activation of astrocytes and microglia in the spinal trigeminal nucleus (Sp5), the main entry pathway for orofacial nociceptive information into the CNS. The morphology and expression of these glial cells will be analyzed through immunohistochemistry, allowing the identification of possible reactive states associated with treatment. This study is expected to contribute to the understanding of the effects of aerobic physical exercise, alone or in combination with CBD, on the modulation of trigeminal neuropathic pain. Furthermore, the findings may clarify the neuroinflammatory mechanisms involved and the role of ascending and descending pathways in the analgesic action of CBD, providing insights for the development of new therapeutic approaches for neuropathic pain. (AU)