Role of dorsal root meninges in chronic pain: unraveling the anatomy and ultrastructure by using Light Sheet Microscopy

• Grant number: 25/01935-0
• Support Opportunities: Scholarships abroad - Research
• Start date: July 01, 2025
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Thiago Mattar Cunha
• Grantee: Thiago Mattar Cunha
• Host Investigator: Dorian Mcgavern
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: McGill University, Canada
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Chronic pain, lasting over three months, significantly affects quality of life, with neuropathic pain being one of its most common forms. This condition results from injuries or diseases affecting the nervous system and is challenging to treat due to the limited effectiveness of available analgesics. Nerve injury leads to biochemical changes that contribute to peripheral and central sensitization, resulting in hyperalgesia and allodynia. Non-neuronal cells, such as glia and immune cells, also play a crucial role in neuropathic pain by releasing inflammatory mediators. Recent research shows that while leukocytes do not infiltrate dorsal root ganglia (DRGs) after injury, they accumulate in the dorsal root meninges, suggesting an immune function in pain modulation. The dorsal root meninges serve as a structural and immunological interface between the central and peripheral nervous systems. However, their interactions with surrounding tissues remain unexplored. Light sheet microscopy (LSM) enables high-resolution, 3D imaging of these structures, offering insights into their role in neuroinflammation and pain. Integrating LSM into the study of dorsal root meninges could revolutionize the understanding of their anatomy and role in pain. Dr. Dorian Mcgarven's group at the NIH has developed advanced imaging techniques to visualize CNS structures in high resolution. This FAPESP Research Fellowship Abroad (RFA) aims to investigate the dorsal root meninges and their interactions with surrounding tissues using LSM. The project seeks to uncover new insights into neuroinflammation and peripheral sensitization, aiding in pain management. Additionally, it will foster collaboration between research groups and facilitate technology transfer to USP and São Paulo. (AU)