RT Journal Article SR Electronic T1 Abnormalities in Hippocampal Functioning with Persistent Pain JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 5747 OP 5756 DO 10.1523/JNEUROSCI.0587-12.2012 VO 32 IS 17 A1 Amelia A. Mutso A1 Daniel Radzicki A1 Marwan N. Baliki A1 Lejian Huang A1 Ghazal Banisadr A1 Maria V. Centeno A1 Jelena Radulovic A1 Marco Martina A1 Richard J. Miller A1 A. Vania Apkarian YR 2012 UL http://www.jneurosci.org/content/32/17/5747.abstract AB Chronic pain patients exhibit increased anxiety, depression, and deficits in learning and memory. Yet how persistent pain affects the key brain area regulating these behaviors, the hippocampus, has remained minimally explored. In this study we investigated the impact of spared nerve injury (SNI) neuropathic pain in mice on hippocampal-dependent behavior and underlying cellular and molecular changes. In parallel, we measured the hippocampal volume of three groups of chronic pain patients. We found that SNI animals were unable to extinguish contextual fear and showed increased anxiety-like behavior. Additionally, SNI mice compared with Sham animals exhibited hippocampal (1) reduced extracellular signal-regulated kinase expression and phosphorylation, (2) decreased neurogenesis, and (3) altered short-term synaptic plasticity. To relate the observed hippocampal abnormalities with human chronic pain, we measured the volume of human hippocampus in chronic back pain (CBP), complex regional pain syndrome (CRPS), and osteoarthritis patients (OA). Compared with controls, CBP and CRPS, but not OA, had significantly less bilateral hippocampal volume. These results indicate that hippocampus-mediated behavior, synaptic plasticity, and neurogenesis are abnormal in neuropathic rodents. The changes may be related to the reduction in hippocampal volume we see in chronic pain patients, and these abnormalities may underlie learning and emotional deficits commonly observed in such patients.