PT633. Involvement of astrocyte Activation in Locus Coeruleus on the Exacerbation of Neuropathic Pain by Maternal Separation and Social Isolation Stress Free

Abstract

In our previous study, emotional dysfunction associated with early life stress exacerbated nerve injury-induced mechanical allodynia, but the mechanism remains unclear. In this study, we investigated the involvement of astrocytes in emotional dysfunction and enhancement of nerve injury-induced mechanical allodynia in mice subjected to maternal separation combined with social isolation (MSSI) as an early life stress. The glial fibrillary acidic protein (GFAP) expression in the locus coeruleus (LC) of female, but not of male mice, significantly increased in MSSI mice corresponding to the behavioral changes at 7–9 weeks of age. Intra-LC injection of conditioned media from cultured astrocytes treated with lipopolysaccharide (LPS) increased GFAP expression, anxiety-like behavior and mechanical allodynia in both male and female mice. These findings demonstrate that emotional dysfunction and enhanced nerve injury-induced mechanical allodynia after exposure to MSSI are mediated, at least in part, by dysfunctional astrocytes in the LC. However, male mice, but not female mice, might show the resistance to MSSI stress during growing.