title: Maternal deprivation is associated with sex-dependent alterations in nociceptive behavior and neuroinflammatory mediators in the rat following peripheral nerve injury.
abstract: 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]). Because neuroimmune signaling 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. MD female, but not male, rats exhibited thermal hypoalgesia and mechanical allodynia compared with 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 compared with non-MD counterparts. Interleukin 6 (IL-6) expression was reduced in the prefrontal cortex of MD-SNL males when compared with non-SNL counterparts. Glial fibrillary acidic protein and IL-1β expression in the hippocampus of MD-SNL males was increased compared with non-MD controls. MD-SNL females exhibited reduced tumor necrosis factor alpha in the prefrontal cortex with a concomitant increase in IL-6 and tumor necrosis factor alpha 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 that may relate to the distinct neuroinflammatory profile observed in female versus male rats.
  
  
  CONCLUSIONS
  This study demonstrates that females rats exposed to early-life stress exhibit enhanced neuropathic pain responding, effects that are associated with alterations in neuroinflammatory mediators. Increased understanding of the interactions among early-life stress, gender, and pain may lead to the identification of novel therapeutic targets for the treatment of chronic pain disorders.
authors.affiliation: Physiology, School of Medicine, NCBES Centre for Pain Research and Galway Neuroscience Centre, National University of Ireland, Galway, Ireland.
authors.forename: Nikita N
authors.initials: NN
authors.lastname: Burke
authors.forename: Ricardo
authors.initials: R
authors.lastname: Llorente
authors.forename: Eva M
authors.initials: EM
authors.lastname: Marco
authors.forename: Kezanne
authors.initials: K
authors.lastname: Tong
authors.forename: David P
authors.initials: DP
authors.lastname: Finn
authors.forename: Maria-Paz
authors.initials: MP
authors.lastname: Viveros
authors.forename: Michelle
authors.initials: M
authors.lastname: Roche
mesh_terms: D000818:Animals; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal; D016207:Cytokines / Q000096:biosynthesis; D005106:Exploratory Behavior; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008026:Ligation; D008262:Macrophage Activation; D008297:Male; D008426:Maternal Deprivation; D009043:Motor Activity; D009437:Neuralgia / Q000378:metabolism / Q000523:psychology; D009457:Neuroglia / Q000502:physiology; D009490:Neurosecretory Systems / Q000503:physiopathology; D059226:Nociceptive Pain / Q000378:metabolism / Q000523:psychology; D010146:Pain / Q000523:psychology*; D010147:Pain Measurement; D059348:Peripheral Nerve Injuries / Q000378:metabolism* / Q000523:psychology*; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D012727:Sex Characteristics; D013127:Spinal Nerves / Q000473:pathology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators
keywords: Maternal deprivation; cold allodynia; cytokines; mechanical allodynia; spinal nerve ligation