Sex-related differences and the role of neuroinflammation in the anti-nociceptive effect of cannabidiol in a model of trigeminal neuralgia

• Grant number: 23/04032-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• End date: May 31, 2024
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Glauce Crivelaro Do Nascimento
• Grantee: Sanderson Araujo da Rocha
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Neuropathic pain may result from central or peripheral nervous system (CNS) injury, being a condition highly resistant to contemporary treatments. Trigeminal neuralgia is a high-intensity and debilitating pain that occurs in the orofacial region, has a multifactorial etiology, and is a therapeutic challenge for health professionals. Chronic pain conditions have important sex-related differences in pain sensitivity threshold and response to pharmacological therapies. In recent years, therefore, there has been a substantial increase in research on sex differences in pain. We hypothesized in this study that CBD has an anti-nociceptive effect in the trigeminal neuralgia model, inducing distinct responses in males and females and that this effect is associated with the reduction of a neuroinflammatory environment in brain areas responsible for descending modulation of pain and input of information. orofacial pain in the CNS. The objective of this study will therefore be to investigate the therapeutic potential of cannabidiol (CBD, 3, 10 and 30mg/kg) on the nociception promoted by an animal model of trigeminal neuralgia and to compare this response in males and females. The trigeminal neuralgia model to be used will be the unilateral constriction of the infraorbital nerve in Wistar-Hannover rats (female and male). The nociceptive response of mechanical allodynia will be evaluated by the Von Frey test and the locomotor activity by the photoelectric actimeter. Cannabidiol (CBD) will be administered intraperitoneally for 7 days (sub-chronic treatment) after establishment of the neuropathic lesion. The Periaqueductal Gray (PAG) is an important component of the descending inhibitory pathway that controls central pain transmission; the spinal trigeminal nucleus (Sp5) is the input structure for orofacial nociceptive information in the CNS. We will evaluate, in these structures, modulation of astrocytes and microglia, as well as their reactive states in these regions, through the analysis of the expression and morphology of these glial cells, by immunohistochemistry. It is expected, through this study, to contribute with the indication of gender-related differences in the nociceptive response induced by trigeminal neuralgia, as well as in the response to analgesic pharmacological therapy. The data to be obtained also seek to elucidate the neuroinflammatory mechanisms involved and the role of ascending and descending modulations of nociceptive information in the pharmacological effect of CBD.