Cannabinoid Modulation of Parkinsonism-Induced Orofacial Manifestations: An Integrated Approach to Pain and Muscle Bioenergetics

• Grant number: 25/13329-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Dentistry - Dental Clinics
• Principal Investigator: Glauce Crivelaro Do Nascimento
• Grantee: Giovanna Caroline Mendes
• 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

Parkinson's Disease (PD) is a progressive neurodegenerative disorder that affects both motor and non-motor functions, including orofacial alterations and myofascial pain, with a significant impact on patients' quality of life. The standard treatment with levodopa (L-DOPA), although effective in controlling motor symptoms, can lead to the development of dyskinesias, whose effects on the masticatory system-particularly the masseter and digastric muscles-are still poorly understood. This project aims to investigate the effects of nigrostriatal lesions induced by 6-hydroxydopamine (6-OHDA) and chronic L-DOPA treatment on the morphological, metabolic, and functional alterations of masticatory muscles in an experimental model of parkinsonism and L-DOPA-induced dyskinesia. Additionally, the therapeutic potential of cannabidiol (CBD)-a phytocannabinoid with anti-inflammatory, analgesic, and bioenergetic-modulating properties-will be evaluated in the attenuation of these changes. The specific objectives are: (1) To assess the effects of CBD on myofascial pain hypersensitivity induced by parkinsonism and L-DOPA-induced dyskinesia; (2) To investigate morphological and metabolic changes in the masseter and digastric muscles through the analysis of myosin fiber types, succinate dehydrogenase activity, and quantification of inflammatory infiltrates (macrophages and neutrophils);(3) To evaluate the impact of CBD treatment on these muscular alterations. It is expected that parkinsonism and L-DOPA treatment will promote muscle dysfunction and orofacial pain, associated with inflammatory processes and metabolic disturbances, and that CBD administration may reverse these effects. The findings of this study may contribute to a better understanding of peripheral mechanisms underlying orofacial manifestations of PD and dyskinesias, and support the validation of CBD as a potential therapeutic approach. Integrating morphological and metabolic analyses of the masticatory musculature may provide translational insights, fostering the development of more effective and comprehensive clinical strategies for managing patients with Parkinson's Disease.