Chronic pain-induced anxiety and gut mucosal homeostasis

• Grant number: 24/19292-6
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2025
• End date: June 30, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Deborah Schechtman
• Grantee: Deborah Schechtman
• Principal researcher abroad: Ivan Eid Tavares de Araújo
• Institution abroad: Max-Planck Institute For Biological Cybernetics, Germany
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Camila Squarzoni Dale
• Associated research grant: 19/06982-6 - Characterization and development of new modulators of the TrkA and PKMzeta pathways in inflammatory and chronic pain, AP.TEM

Abstract

The primary objective of this proposal is to identify the biological factors underlying the immunological and proinflammatory processes characteristic of chronic pain and specifically to establish whether the impact of chronic pain on gut mucosal homeostasis mediates systemic inflammation. Chronic pain is a refractory health disease that imposes significant economic burden on affected individuals. Growing evidence indicates that otherwise unexplained inflammatory processes are the primary contributors to chronic pain development. Chronic pain and inflammation coexist with anxiety and depression symptoms. Such psychological changes may intensify pro-inflammatory signs and pain. It is now known that chronic psychological stress leads to a marked decrease in the activity of the parasympathetic neurons of the vagus nerve and, as a byproduct, suppresses parasympathetic-driven secretion of protective factors by duodenal Brunner's glands. In the present study, we intend to test the hypothesis that the psychological impact of chronic pain suppresses Brunner's gland secretions, leading to dysbiosis and the expression of inflammatory markers. This, in turn, leads to an exaggeration of pain-associated behaviors. We specifically aim to identify the secreted factors affected by chronic pain that mediate the anti-inflammatory actions of Brunner's glands secretions. This hypothesis supports the idea that the gut-brain axis is key to pain and can be targeted for pain treatment. (AU)