Systemic treatment with cannabidiol in rats of high and low freezing carioca lines in the chronic pain model: evaluation of pain sensitivity, affective component of pain, anxiety and its expression of BDNF

• Grant number: 19/22120-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): May 01, 2020
• Effective date (End): April 30, 2023
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Christie Ramos Andrade Leite Panissi
• Grantee: Carolina Macêdo de Souza
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/50891-1 - INCT 2014: Translational Medicine, AP.TEM

Abstract

Epidemiological studies show that Generalized Anxiety Disorder (GAD) and chronic pain are highly prevalent and debilitating diseases in the world. GAD refers primarily to a persistent and excessive state of worry, while chronic pain is a pain that persists or repeats after recovery phase of an injury. Concomitant to these data, chronic or persistent pain is related to various psychiatric disorders and several studies demonstrate that individuals with GAD are considerably susceptible to comorbidity with chronic pain. In this scenario, the incidence of studies in the literature on the neurobiological mechanisms responsible for triggering the processes of this relationship between pain and anxiety is increasing. Although they are independent systems, there is partially an overlapping of the neural substrates corresponding to fear/anxiety and pain, among them: the hippocampus, the amygdala, the Anterior Cingulate Cortex (ACC). In addition, studies suggest that in this interaction a significant action of neuroplasticity occurs. However, the neurobiological mechanisms responsible for this action are still not well known. A valid and reliable means of studying these behavioral and neurochemical mechanisms is through the use of animal models. Considering the neurochemistry involved in nociceptive modulation, the cannabinoid system is an important endogenous system that participates in the pain sensitivity circuit, also functioning as a modulator of the affective and cognitive aspects of pain and anxiety. Therefore, this study will aim to investigate such interactions in an animal model of contextual fear anxiety (TAG model), the rats of high and low freezing Cariocas strains. Will perform a chronic systemic treatment with cannabidiol (CBD) in chronic or acute pain model in the Carioca lineages. In particular, it will be evaluated whether the administration of CBD specifically alters the behavioral response to acute (thermal and mechanical) noxious stimuli, that is, the discriminating component of pain, and/or the motivational affective component (pain aversion). To achieve this goal, the von Frey test, hot plate test and acetone test, and the local avoidance/avoidance (PEAP) paradigm will be used. In a second step, the expression of the neurotrophic factor (BDNF) will be evaluated in brain areas involved in the modulation of the affective-motivational component of pain and anxiety. Considering these objectives we intend to understand in this animal model of GAD the mechanisms that would be involved in the interaction of chronic pain and anxiety related to neurogenesis in the brain areas addressed in this study. (AU)