Pain is a complex sensory and emotion experience that typically facilitates a learning event so that an individual may avoid future harm. However, in a chronic pain context, pain that is experienced at inappropriate times no longer provides a useful function and may impair learning. Cognitive deficits including difficulties with learning and memory recall have been well documented in the clinic but pre-clinical data is lacking and the neural basis remains poorly understood. Using a chronic constriction injury (CCI) model of neuropathic pain in mice, combined with ex vivo electrophysiology and spatial memory tasks we found marked differences in basal synaptic transmission at CA3-CA1 synapses of the hippocampus compared to sham controls. In addition, two forms of long-term potentiation were markedly impaired in CCI mice compared to controls. Intriguingly, we found this impairment was lateralised to specific hemispheres, which were dependent on injury site and the type of synaptic plasticity studied. Consistent with altered hippocampus function, we also found mice with the CCI injury displayed impaired spatial recognition memory on the Y-maze task. Together these data provide evidence that neuropathic pain alters the function of a key memory centre of the brain, suggesting neuroadaptations associated with chronic pain are not limited to conventional pain circuits.