Effect of CBD treatment on experimental chronic stress-induced fibromyalgia: involvement of D1, D2 and CB1 type receptors of the NAcc

• Grant number: 24/03983-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2024
• End date: February 29, 2028
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Carlos Amilcar Parada
• Grantee: Ana Carolina dos Santos Machado
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Epidemiological studies highlight the association between social stress and the development of depression and anxiety, as well as the comorbidity between these disorders and chronic pain. Chronic pain causes suffering and even disability, having high clinical relevance and impact on quality of life. The participation of the mesolimbic dopaminergic system in the chronification of pain has been established, with the nucleus accumbens (NAc) being an important brain structure in this process, presenting accentuated neurochemical activity in situations of chronic stress, in addition to acting in the descending modulation of pain. In recent years, our research group has demonstrated the involvement of the NAc dopaminergic system in the chronicity of inflammatory pain. Dopaminergic neurotransmission in the NAc is modulated by receptors from the dopaminergic system (type D1 and D2) and other endogenous systems, such as endocannabinoid, with important expression of CB1 receptors. The search for effective and safe treatments for managing chronic pain continues to increase, with interest in the use of cannabidiol (CBD), a non-psychoactive molecule derived from the Cannabis sativa plant with important analgesic, anti-inflammatory and anxiolytic effects. Clinical and pre-clinical studies demonstrate the positive effect of CBD in the management of chronic pain. There are also studies demonstrating CBD as a modulator of the mesolimbic dopaminergic system. In this context, we suggest studying the participation of the NAc dopaminergic system in the establishment of chronic pain in a fibromyalgia model, due to its association with stress, and the involvement of D1 and D2 type dopaminergic receptors in this process. We also suggest investigating the analgesic effect of CBD on chronic pain induced by chronic stress, as well as the participation of CB1 cannabinoid receptors in the NAc in the analgesic effect and in modulating the amounts of dopamine in the structure.