Abstract # 3205 The Role of Microglia in the Development and Exacerbation of Stress-Induced Pain Behavior

Numerous clinical studies indicate that stress influences the development of pain, but it is not clear how pain is initiated or amplified by stress. Exposure to psychosocial stress disrupts the homeostatic communication pathways between the central nervous system and peripheral immune system, leading to dysregulated and heightened neuroinflammation. Related to this, pain development is associated with production of inflammatory mediators within the spinal cord that can facilitate transmission of pain into the brain. Repeated social defeat (RSD) is a mouse model of psychosocial stress that activates resident microglia, increases release of inflammatory markers, and promotes behavioral changes including pain and anxiety. We hypothesize that microglia in the spinal cord induce pain behavior during stress through enhanced production of inflammatory mediators. Here we show that RSD-induced mechanical allodynia corresponded with increased inflammatory gene expression in the spinal cord. Moreover, mechanical allodynia during RSD corresponded with spinal cord region-specific microglial activation in areas involved with pain synapses. Microglial depletion with a colony stimulating factor 1 receptor antagonist prior to stress prevented the development of mechanical allodynia associated with RSD. Furthermore, RSD-induced inflammation in the spinal cord was reduced by microglial depletion. These findings indicate that exposure to repeated social stress promotes increased microglia-dependent pain behavior through heightened inflammation in the spinal cord. Therefore, microglia may serve as a potential cellular target to alleviate stress-induced pain symptoms. This study was supported by National Institute of Health (NIMH) grants R01-MH-093473 and R01-MH-093472 to JFS. MDW and BLJ were supported by NIDCR Training Grant T32-DE014320. CMS was supported by F30-DE026075.