Abstract # 1773 Cytotoxic T cells may induce pain hypersensitivity in female but not male mice after nerve injury in an interferon-g-receptor-dependent manner

In our previous study, we observed that female mice, unlike males, do not require microglia to produce pain hypersensitivity after neuropathic or inflammatory injury. Using T-cell deficient mice, we found that female mutant mice “switch” to the “male” microglial system. Important questions include how microglial or T cell systems are recruited, how and which T cells are infiltrating into the spinal cord, and what T cells are releasing that can sensitize pain-relevant neurons. Immune cells were extracted from lumbar spinal cord of WT mice and IFNgRKO mice post SNI and CFA injection, and analyzed using flow cytometry. Additionally, mechanical allodynia was assessed. Analyzing the spinal cord microenvironment after SNI revealed that female mice displayed: (1) a 2-fold increase in CD8+ cytotoxic T cells, (2) upregulation of the anti-inflammatory microglia population, and (3) downregulation of anti-inflammatory T regulatory cells and pro-inflammatory microglia. In contrast, males showed: (1) a 2-fold decrease in CD8+ cytotoxic T cells, and (2) an increase in pro-inflammatory microglia. IFNgRKO female mice showed the same pain behavioural response as WT males wherein minocycline reversed allodynia. Consistent with this, IFNgRKO female, like WT male, mice did not show upregulation of CD8+ cytotoxic T cells. Our current data further suggest that female mice, unlike males, are using cytotoxic CD8+ T cells to induce neuropathic pain, and that this mechanism appears to be dependent on IFNgRs.