Cellular and molecular characterization and origin of the leukocytes accumulated in the leptomeninges of the dorsal roots of neuropathic animals

• Grant number: 21/00840-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2022
• End date: April 30, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Thiago Mattar Cunha
• Grantee: William Antonio Gonçalves
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Injuries and diseases that affect the somatosensory system lead to the neuropathic pain development. The genesis and maintenance of this condition is determined by changes in the nociceptive sensory apparatus that increase painful sensitivity. Much of these changes are mediated by the activity of immune cells in the central and peripheral pain modulating sites, such as the spinal cord or Dorsal Root Ganglia (DRG). In addition, unpublished data from our group indicate that peripheral nerve injury is related to accumulation of immune cells in the leptomeninge of the dorsal roots and spinal cord, resulting in an ectopic tissue close to the DRG and the spinal cord superior area. However, the cellular and molecular profile of the immune cells in leptomeninges and also the route by which these cells migrate are unclear. Thus, the aim of this project is to identify the populations of immune cells that are recruited, characterizing their transcriptional profile and also the route by which these cells access the leptomeninges. In this way, we will use single cell transcriptome sequencing (scRNAseq). This resource will precisely determine the profile of the immune cell populations recruited to the ectopic leptomeninges tissue formed after peripheral nerve injury. In addition, we will investigate the bone structures used by immune cells as a pathway to access the leptomeninges during neuropathic pain development. Microcomputed tomography (¼-CT) images obtained by our group revealed the existence of microscopic channels in vertebrae connecting the bone marrow to the nervous tissue surface. These findings suggest that the recruited of immune cells to the neuropathic animals leptomeninge may have come from its vertebral bone marrow. From this point of view, our project may contribute with clinical perspectives for neuropathic pain treatment by inhibiting the action of the specific type of immune cells present in the leptomeninges and blocking the access of these cells after peripheral nerves injury. (AU)