Early-life stress is associated with an increased risk of developing affective disorders and chronic pain conditions. This study examined the effect of maternal deprivation (MD) on nociceptive responding prior to and following peripheral nerve injury (L5-L6 spinal nerve ligation (SNL)). As neuroimmune signalling plays an important role in pain and affective disorders, associated alterations in glial and cytokine expression were assessed in key brain regions associated with emotional and nociceptive responding, the hippocampus and prefrontal cortex (PFC). MD female, but not male, rats exhibited thermal hypoalgesia and mechanical allodynia when compared to control (non-MD) counterparts. SNL resulted in mechanical and cold allodynia in MD and control rats of both sexes. However, MD females exhibited enhanced SNL-induced allodynic responding when compared to non-MD counterparts. IL-6 expression was reduced in the PFC of MD-SNL males when compared with non-SNL counterparts. GFAP and IL-1β expression in the hippocampus of MD-SNL males was increased compared with non-MD controls. MD-SNL females exhibited reduced TNFα in the PFC with a concomitant increase in IL-6 and TNFα expression in the hippocampus, compared with either MD or SNL alone. In conclusion, MD female, but not male, rats exhibit enhanced nociceptive responding following peripheral nerve injury, effects which may relate to the distinct neuroinflammatory profile observed in female versus male rats.