title: Neonatal repetitive pain in rats leads to impaired spatial learning and dysregulated hypothalamic-pituitary-adrenal axis function in later life.
abstract: Preterm birth is a major health issue. As part of their life-saving care, most preterm infants require hospitalization and are inevitably exposed to repetitive skin-breaking procedures. The long-term effects of neonatal repetitive pain on cognitive and emotional behaviors involving hypothalamic-pituitary-adrenal (HPA) axis function in young and adult rats are unknown. From P8 to P85, mechanical hypersensitivity of the bilateral hindpaws was observed in the Needle group (P < 0.001). Compared with the Tactile group, the Needle group took longer to find the platform on P30 than on P29 (P = 0.03), with a decreased number of original platform site crossings during the probe trial of the Morris water maze test (P = 0.026). Moreover, the Needle group spent more time and took longer distances in the central area than the Tactile group in the Open-field test, both in prepubertal and adult rats (P < 0.05). The HPA axis function in the Needle group differed from the Tactile group (P < 0.05), with decreased stress responsiveness in prepuberty and puberty (P < 0.05) and increased stress responsiveness in adulthood (P < 0.05). This study indicates that repetitive pain that occurs during a critical period may cause severe consequences, with behavioral and neuroendocrine disturbances developing through prepuberty to adult life.
authors.affiliation: Department of Child Health Care, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Mengying
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Child Health Care, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Xia
authors.affiliation: Department of Child Health Care, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Cuiting
authors.initials: C
authors.lastname: Min
authors.affiliation: Department of Rehabilitation, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Child Health Care, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yinhua
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Applied Physics and Electronics, Umeå University, Umeå, Sweden.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Child Health Care, Children's Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D010146:Pain / Q000150:complications* / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000209:etiology / Q000503:physiopathology*