Repetitive Pain in Neonatal Male Rats Impairs Hippocampus-Dependent Fear Memory Later in Life

Xia, Dongqing; Min, Cuiting; Chen, Yinhua; Ling, Ru; Chen, Mengying; Li, Xiaonan

doi:10.3389/fnins.2020.00722

Cited by 17 publications

(16 citation statements)

References 68 publications

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“…If the animal learns this association, they will respond to the conditioned stimulus (context or cue) with a characteristic freezing posture. Neonatal inflammation attenuated conditioned freezing in adolescence and early adulthood, suggesting an impaired memory for fear stimuli (Davis et al, 2018(Davis et al, , 2021Xia et al, 2020). This effect appears to reverse with age, as older adults that experienced inflammation early in life showed sustained fear responses to a conditioned cue (Doenni et al, 2017) or context (Tishkina et al, 2016).…”

Section: Fearmentioning

confidence: 99%

Early Life Painful Procedures: Long-Term Consequences and Implications for Farm Animal Welfare

Adcock

2021

Front. Anim. Sci.

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Farm animals routinely undergo painful husbandry procedures early in life, including disbudding and castration in calves and goat kids, tail docking and castration in piglets and lambs, and beak trimming in chicks. In rodents, inflammatory events soon after birth, when physiological systems are developing and sensitive to perturbation, can profoundly alter phenotypic outcomes later in life. This review summarizes the current state of research on long-term phenotypic consequences of neonatal painful procedures in rodents and farm animals, and discusses the implications for farm animal welfare. Rodents exposed to early life inflammation show a hypo-/hyper-responsive profile to pain-, fear-, and anxiety-inducing stimuli, manifesting as an initial attenuation in responses that transitions into hyperresponsivity with increasing age or cumulative stress. Neonatal inflammation also predisposes rodents to cognitive, social, and reproductive deficits, and there is some evidence that adverse effects may be passed to offspring. The outcomes of neonatal inflammation are modulated by injury etiology, age at the time of injury and time of testing, sex, pain management, and rearing environment. Equivalent research examining long-term phenotypic consequences of early life painful procedures in farm animals is greatly lacking, despite obvious implications for welfare and performance. Improved understanding of how these procedures shape phenotypes will inform efforts to mitigate negative outcomes through reduction, replacement, and refinement of current practices.

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Section: Fearmentioning

confidence: 99%

Early Life Painful Procedures: Long-Term Consequences and Implications for Farm Animal Welfare

Adcock

2021

Front. Anim. Sci.

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“…Повторные болевые воздействия в неонатальном возрасте вызывают структурные и функциональные изменения в областях мозга, связанных с адаптивным поведением (Chen et al 2016;Xia et al 2020). Клинические данные по исследованию влияния неонатального болевого стресса на адаптивную гипоталамо-гипофизарно-адренокортикальную систему (ГГАКС) ограничены подростковым возрастом и получены на детях, которые родились раньше срока и нуждались в интенсивных терапевтических процедурах (Brummelte et al 2015;Grunau et al 2005; Mooney-Leber, Brummelte 2017).…”

Section: Introductionunclassified

The impact of neonatal inflammatory pain on cognitive and stress-reactive functions in adult male and female rats

Mikhailenko¹,

Butkevich²,

Vershinina³

2022

Integrative Physiology

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Repetitive neonatal pain may cause central nervous system disorders. Existing clinical data on the effect of neonatal pain on learning, memory and stress-reactivity of the hypothalamic-pituitary-adrenal axis (the HPA axis) are limited to adolescence and have mostly been obtained for male individuals. The mechanism of neonatal pain effect has not yet been researched. Ontogenetic studies carried out on different-sex specimen are crucial for prediction, prevention and treatment of adaptive behavioural disorders caused by neonatal pain stress. Lately, this has become even more relevant due to COVID-19 affecting new-borns in need of intensive therapy. In this study, the impact of neonatal inflammatory pain on adult cognition and hormonal stress response was investigated in male and female rats. Continuous neonatal pain was induced by hindpaw formalin injections on days one and two from birth. In adult rats, we assessed spatial learning and memory using the Morris water maze and evaluated HPA reactivity in response to the formalin test. No significant cognitive function differences were found between the experimental group of rats subjected to neonatal pain and the control group. Within the experimental group subjected to neonatal pain, males showed better long-term spatial memory than females. After testing the long-term memory, we evaluated HPA reactivity by corticosterone levels in response to a formalin test. This parameter was higher in males. Only females with neonatal pain showed differences between short-term and long-term memory, with poorer long-term memory. Possible causes of sex differences in the cognitive function and hormonal stress response in adult rats exposed to neonatal inflammatory pain are discussed.

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“…Adolescence is characterized by intensive processes of synaptogenesis and myelinization, especially in the prefrontal cortex, hippocampus and amygdala ( Brenhouse and Andersen, 2011 ), reorganization in the hormonal, neurotransmitter, and reproductive systems ( McCormick et al, 2004 , 2016 ; Romeo and McEwen, 2006 ; Romeo, 2010 ; McCormick, 2011 ), and behavioral and cognitive maturation ( McCormick and Mathews, 2010 ; McCormick et al, 2012 ; Siddiqui and Romeo, 2019 ). The trajectory of these processes in adolescence can be altered by neonatal stress, including clinically necessary painful procedures ( Amaral et al, 2015 ; Chen et al, 2016 ; Mooney-Leber and Brummelte, 2017 ; Xia et al, 2020 ), which can modify behavior and cognitive abilities in adolescents ( Mooney-Leber and Brummelte, 2020 ; see Williams and Lascelles, 2020 for a review). Thus, early-life pain can give rise to numerous clinical, social, educational problems in adolescents which may differ from those of adults.…”

Section: Introductionmentioning

confidence: 99%

“…Most of the basic research has been and is being done on males ( Chen et al, 2016 ; Xia et al, 2020 ). When both sexes are tested, females have been found to be more vulnerability to the noxious influences at an early age by some ( Gildawie et al, 2021 ), whereas others report increased vulnerability in males ( Van Dammen et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

The Long-Term Effects of Neonatal Inflammatory Pain on Cognitive Function and Stress Hormones Depend on the Heterogeneity of the Adolescent Period of Development in Male and Female Rats

Butkevich

Mikhailenko

Vershinina

et al. 2021

Front. Behav. Neurosci.

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Exposure to stress at an early age programs the HPA axis which can lead to cognitive deficits in adults. However, it is not known whether these deficits emerge in adulthood or are expressed earlier in life. The aims of the study were to investigate (1) the immediate effects of early injury-induced stress in one-day-old (P1) and repeated stress on at P1 and P2 rat pups on plasma corticosterone levels; and (2) examine the subsequent long-term effects of this early stress on spatial learning and memory, and stress reactivity in early P26-34 and late P45-53 adolescent male and female rats. Intra-plantar injection of formalin induced prolonged and elevated levels of corticosterone in pups and impaired spatial learning and short- and long-term memory in late adolescent males and long-term memory in early adolescent females. There were sex differences in late adolescence in both learning and short-term memory. Performance on the long-term memory task was better than that on the short-term memory task for all early adolescent male and female control and stressed animals. Short-term memory was better in the late age control rats of both sexes and for formalin treated females as compared with the early age rats. These results are consistent with an impaired function of structures involved in memory (the hippocampus, amygdala, prefrontal cortex) after newborn pain. However, activation of the HPA axis by neonatal pain did not directly correlate with spatial learning and memory outcomes and the consequences of neonatal pain remain are likely multi-determined.

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Repetitive Pain in Neonatal Male Rats Impairs Hippocampus-Dependent Fear Memory Later in Life

Cited by 17 publications

References 68 publications

Early Life Painful Procedures: Long-Term Consequences and Implications for Farm Animal Welfare

Early Life Painful Procedures: Long-Term Consequences and Implications for Farm Animal Welfare

The impact of neonatal inflammatory pain on cognitive and stress-reactive functions in adult male and female rats

The Long-Term Effects of Neonatal Inflammatory Pain on Cognitive Function and Stress Hormones Depend on the Heterogeneity of the Adolescent Period of Development in Male and Female Rats

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