Distinct neuro-immune interactions drive sex differences in chronic pain

Project Overview

One of the most important advances in our understanding of chronic pain over the last decade or so is the realization that neurons are not the only cells in the central nervous system participating in the processing of pain signals. Immune-like “glial” cells (especially microglia and astrocytes), thought previously to play mere structural supporting roles, are now known to be active players in pain processing, containing and releasing key molecules that themselves represent excellent novel targets for the development of analgesic drugs. As is typical in pain research and biomedical research in general, virtually every one of the studies demonstrating the important role of these “neuro-immune” interactions between glial cells and neurons in the spinal cord was performed on male rats or mice. Jeffrey Mogil and his team have already convincingly demonstrated that spinal cord microglia are not required for the development of chronic pain in female mice as they are in males. This particular project goal is to examine, for the first time, the role of glial molecules in pain in female mice and rats. Furthermore, as they now believe that sex differences in pain are robust and widespread, they will search for sex differences in brain function above the level of the spinal cord in mice using cutting-edge imaging techniques (high-field MRI and serial two-photon tomography). Finally, to establish the likely relevance of these findings to humans, they will conduct experiments in Macaca fascicularis and look for sex differences in gene and protein levels after pain-related nerve damage in this primate species.

Partners and Donors

Université Laval

McGill University

The Hospital for Sick Children