title: Abnormalities in hippocampal functioning with persistent pain.
abstract: 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.
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Amelia A
authors.initials: AA
authors.lastname: Mutso
authors.forename: Daniel
authors.initials: D
authors.lastname: Radzicki
authors.forename: Marwan N
authors.initials: MN
authors.lastname: Baliki
authors.forename: Lejian
authors.initials: L
authors.lastname: Huang
authors.forename: Ghazal
authors.initials: G
authors.lastname: Banisadr
authors.forename: Maria V
authors.initials: MV
authors.lastname: Centeno
authors.forename: Jelena
authors.initials: J
authors.lastname: Radulovic
authors.forename: Marco
authors.initials: M
authors.lastname: Martina
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Miller
authors.forename: A Vania
authors.initials: AV
authors.lastname: Apkarian
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D001973:Bromodeoxyuridine; D003213:Conditioning, Psychological / Q000502:physiology; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005239:Fear; D005247:Feeding Behavior; D018756:GABA Antagonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000473:pathology*; D006930:Hyperalgesia / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010852:Picrotoxin / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D012585:Sciatica / Q000473:pathology* / Q000503:physiopathology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D015763:2-Amino-5-phosphonovalerate; D001973:Bromodeoxyuridine; D000089622:Doublecortin Domain Proteins; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D049452:Green Fluorescent Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010751:Phosphopyruvate Hydratase; D010852:Picrotoxin; D011494:Protein Kinases; C485184:enhanced green fluorescent protein