Chronic pain is a clinically relevant health care issue that affects millions of people worldwide with very limited effective therapeutic treatments. For the development of new, safe and effective therapeutic strategies critical knowledge gaps about pain mechanisms in the brain need to be addressed. Increasing evidence has demonstrated a role for neuroimmune signaling factors in the pathogenesis of chronic pain. Within the brain the amygdala, a bilateral limbic structure, plays a key role in the emotional-affective dimensions of pain and pain modulation. Preliminary evidence has suggested pain-related functional lateralization in the amygdala particularly within the central nucleus (CeA) which serves major output functions. Whereas a pro-nociceptive phenotype has been characterized in the right CeA across various pain models, the role of left CeA in pain remains unclear. Additionally, little has been explored with regard to pain-related lateralization of neuroimmune signaling mechanisms in the CeA, particularly following exogenous stimulation. This study explored the effects of neuroinflammation induced by the exogenous microinjection of lipopolysaccharide (LPS), a component of gram-negative bacteria and a strong immunostimulant, in the right or left CeA on pain-related behaviors. LPS was stereotaxically delivered into the left or right CeA of male and female rats and 3 or 7 days post-surgery sensory thresholds (von Frey test and paw pressure), anxiety-like behaviors (elevated plus maze, EPM, and open field test, OFT) and emotional-affective behaviors (evoked vocalizations) were measured. Intra-CeA LPS injections produced anxiety-like behaviors and decreased sensory withdrawal thresholds, regardless of hemisphere. The results suggest that exogenous activation of neuroimmune signaling into the right CeA generate affective behaviors in male and female animals. Neuroinflammation in both right and left CeA induced hypersensitivity in both sexes with more pronounced effects at 3 rather than 7 days post-LPS injection. The results suggest the involvement of mechanisms that might be sex-, time-, and side- specific supporting the idea that further mechanistic insight into the functional lateralization of amygdala pain processing are needed for the development of effective therapeutic strategies to alleviate the chronic pain.