Rostral ventromedial medulla: what is its role in behavioral changes induced by social stress?

• Grant number: 22/06332-4
• Support Opportunities: Generation Project Research Grant
• Start date: December 01, 2024
• End date: November 30, 2029
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Marco Oreste Finocchio Pagliusi Junior
• Grantee: Marco Oreste Finocchio Pagliusi Junior
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Andre Schwambach Vieira ; Felipe Villela Gomes ; Francisco Silveira Guimaraes ; Mary Kay Lobo ; Sabrina Francesca de Souza Lisboa
• Associated scholarship(s): 24/21018-0 - Rostral ventromedial medulla: what is its role in behavioral changes induced by social stress?, BP.GR

Abstract

Major depressive disorder (MDD) affects a significant portion of the world population, being diagnosed mainly through criteria established by the Diagnostic and Statistical Manual of Mental Disorders (DSM). Although chronic pain is not among the symptoms of depression described by the DSM, epidemiological studies indicate a close association between MDD and chronic pain. The social defeat stress (SDS) model is currently being used to induce depressive-like behaviors and persistent hyperalgesia in mice. In this model, mice are exposed for 10 consecutive days to an aggressive mouse of a physically robust strain, suffering brief periods of physical aggression followed by longer periods of visual and olfactory contact. It has been shown that the SDS-induced chronic pain resembles human fibromyalgia, a condition characterized by widespread chronic pain and closely associated with depression symptoms. It is known that the experience of pain, in all its complexity, involves the perception of a series of factors integrated by the central nervous system (CNS), mainly by the cerebral cortex. This integrative process is extremely dynamic, being continuously adjusted to day-to-day demands. It is known that pain starts from the activation of peripheral nociceptors which send ascending neural signals to higher levels of the CNS through specific neural pathways. These ascending pathways are modulated by descending supraspinal pathways, which serve as an endogenous system of analgesia or pain facilitation. An important brain structure associated with descending pain modulation is the rostral ventromedial medulla (RVM). The RVM has a key role in both facilitatory and inhibitory systems of pain, receiving projections from several brain structures such as periaqueductal gray matter, nucleus accumbens and anterior cingulate cortex. Not surprisingly, the aforementioned neural structures are also related to depressive behavior. Data obtained during my first postdoctoral year demonstrated the participation of RVM in SDS-induced pain and, interestingly, in SDS-induced depressive-like behaviors. These data prompted new questions that helped to conceive the present proposal. Therefore, this proposal aims to study in depth the participation of RVM in SDS-induced behavioral impairments. For this, the proposal will be divided into 4 projects. Briefly, the first project will investigate whether a modified social stress model for females is capable of inducing persistent hyperalgesia and whether RVM will interfere with stress-induced behavioral impairments, as we already demonstrated in males. The second project will analyze the influence of neuronal projection to the RVM on the behavioral impairments induced by social stress. The third project proposes to evaluate the changes in the RVM transcriptome and its projections in the social stress context. Finally, the fourth project aims to investigate the RVM activation in the social stress context. (AU)