The impact of neonatal inflammatory pain on cognitive and stress-reactive functions in adult male and female rats
DOI:
https://doi.org/10.33910/2687-1270-2022-3-1-69-79Keywords:
pain stress, neonatal period, adult rat, spatial learning, memory, corticosteroneAbstract
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.
References
Akirav, I., Kozenicky, M., Tal, D. et al. (2004) A facilitative role for corticosterone in the acquisition of a spatial task under moderate stress. Learning and Memory, vol. 11, no. 2, pp. 188–195. http://www.learnmem.org/cgi/doi/10.1101/lm.61704 (In English)
Amaral, C., Antonio, B., Oliveira, M. G. M. et al. (2015) Early postnatal nociceptive stimulation results in deficits of spatial memory in male rats. Neurobiology of Learning and Memory, vol. 125, pp. 120–125. https://doi.org/10.1016/j.nlm.2015.08.012 (In English)
Anand, K. J., Garg, S., Rovnaghi, C. R. et al. (2007) Ketamine reduces the cell death following inflammatory pain in newborn rat brain. Pediatric Research, vol. 62, no. 3, pp. 283–290. https://doi.org/10.1203/pdr.0b013e3180986d2f (In English)
Behuet, S., Cremer, J. N., Cremer, M. et al. (2019) Developmental changes of glutamate and GABA receptor densities in wistar rats. Frontiers in Neuroanatomy, vol. 13, article 100. https://doi.org/10.3389/fnana.2019.00100 (In English)
Bonapersona, V., Kentrop, J., Van Lissa, C. J. et al. (2019) The behavioral phenotype of early life adversity: A 3-level meta-analysis of rodent studies. Neuroscience and Biobehavior Review, vol. 102, pp. 299–307. https://doi.org/10.1016/j.neubiorev.2019.04.021 (In English)
Brewer, C. L., Baccei, M. L. (2020) The development of pain circuits and unique effects of neonatal injury. Neural Transmission, vol. 127, no. 4, pp. 467–479. https://doi.org/10.1007/s00702-019-02059-z (In English)
Brummelte, S., Chau, C. M. Y., Cepeda, I. L. et al. (2015) Cortisol levels in former preterm children at school age are predicted by neonatal procedural pain-related stress. Psychoneuroendocrinology, vol. 51, pp. 151–163. https://doi.org/10.1016/j.psyneuen.2014.09.018 (In English)
Butkevich, I., Mikhailenko, V., Semionov, P. et al. (2009) Effects of maternal corticosterone and stress on behavioral and hormonal indices of formalin pain in male and female offspring of different ages. Hormones and Behavior, vol. 55, no. 1, pp. 149–157. https://doi.org/10.1016/j.yhbeh.2008.09.008 (In English)
Butkevich, I. P., Mikhailenko, V. A., Vershinina, E. A. (2020) Combination of stressors in the critical periods of development increases resistance to inflammatory pain stress in adult rats. Neuroscience and Behavior Physiology, vol. 50, no. 8, pp. 1090–1097. https://doi.org/10.1007/s11055-020-01010-0 (In English)
Butkevich, I. P., Mikhailenko, V. A., Vershinina, E. A., Barr, G. A. (2021) 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. Frontiers in Behavior Neuroscience, vol. 15, article 691578. https://doi.org/10.3389/fnbeh.2019.00125 (In English)
Chen, M., Xia, D., Min, C. et al. (2016) Neonatal repetitive pain in rats leads to impaired spatial learning and dysregulated hypothalamic-pituitary-adrenal axis function in later life. Scientific Reports, vol. 14, article 39159. https://doi.org/10.1038/srep39159 (In English)
Daskalakis, N. P., Bagot, R. C., Parker, K. J. (2013) The three-hit concept of vulnerability and resilience: Toward understanding adaptation to early-life adversity outcome. Psychoneuroendocrinology, vol. 38, no. 9, pp. 1858–1873. https://doi.org/10.1016/j.psyneuen.2013.06.008 (In English)
Dührsen, L., Simons, S. H., Dzietko, M. et al. (2013) Effects of repetitive exposure to pain and morphine treatment 742 on the neonatal rat brain. Neonatology, vol. 103, no. 1, pp. 35–43. https://doi.org/10.1159/000341769 (In English)
Fitzgerald, E., Sinton, M. C., Wernig-Zorc, S. et al. (2021) Altered hypothalamic DNA methylation and stress-induced hyperactivity following early life stress. Epigenetics Chromatin, vol. 14, no. 1, article 31. https://doi.org/10.1186/s13072-021-00405-8 (In English)
Green, M. R., McCormick, C. M. (2016) Sex and stress steroids in adolescence: Gonadal regulation of the hypothalamic-pituitary-adrenal axis in the rat. General and Comparative Endocrinology, vol. 234, pp. 110–116. https://doi.org/10.1016/j.ygcen.2016.02.004 (In English)
Grunau, R. E., Holsti, L., Haley, D. W. et al. (2005) Neonatal procedural pain exposure predicts lower cortisol and behavioral reactivity in preterm infants in the NICU. Pain, vol. 113, no. 3, pp. 293–300. https://doi.org/10.1016/j.pain.2004.10.020 (In English)
Grunau, R. E., Holsti, L., Peters, J. W. (2006) Long-term consequences of pain in human neonates. Seminars in Fetal and Neonatal Medicine, vol. 11, no. 4, pp. 268–275. https://doi.org/10.1016/j.siny.2006.02.007 (In English)
Grunau, R. E., Whitfield, M. F., Petrie-Thomas, J. et al. (2009) Neonatal pain, parenting stress and interaction, in relation to cognitive and motor development at 8 and 18 months in preterm infants. Pain, vol. 143, no. 1–2, pp. 138–146. https://doi.org/10.1016/j.pain.2009.02.014 (In English)
Grunau, R. E., Cepeda, I. L., Chau, C. M. et al. (2013) Neonatal pain-related stress and NFKBIA genotype are associated with altered cortisol levels in preterm boys at school age. PLoS One, vol. 8, no. 9, article e73926. https://doi.org/10.1371/journal.pone.0073926 (In English)
Gulchina, Y., Xu, S-J., Snyder, M. A. et al. (2017) Epigenetic mechanisms underlying NMDA receptor hypofunction in the prefrontal cortex of juvenile animals in the MAM model for schizophrenia. Journal of Neurochemistry, vol. 143, no. 3, pp. 320–333. https://doi.org/10.1111/jnc.14101 (In English)
Henderson, Y. O., Victoria, N. C., Inoue, K. et al. (2015) Early life inflammatory pain induces long-lasting deficits in hippocampal-dependent spatial memory in male and female rats. Neurobiology of Learning and Memory, vol. 118, pp. 30–41. https://doi.org/10.1016/j.nlm.2014.10.010 (In English)
Herrington, С. J., Olomu, I. N., Geller, S. M. (2004) Salivary cortisol as indicators of pain in preterm infants: A pilot study. Clinical Nursing Research, vol. 13, no. 1, pp. 53–68. https://doi.org/10.1177/1054773803259665 (In English)
Hrabovszky, E., Wittmann, G., Turi, G. F. et al. (2005) Hypophysiotropic thyrotropin-releasing hormone and corticotropin-releasing hormone neurons of the rat contain vesicular glutamate transporter-2. Endocrinology, vol. 146, no. 1, pp. 341–347. https://doi.org/10.1210/en.2004-0856 (In English)
Khawla, Q., Alzoubi, N. K. H., Alhusban, A. et al. (2017) Sucrose and naltrexone prevent increased pain sensitivity and impaired long-term memory induced by repetitive neonatal noxious stimulation: Role of BDNF and β-endorphin.Physiology and Behavior, vol. 179, pp. 213–219. https://doi.org/10.1016/j.physbeh.2017.06.015 (In English)
Koutmani, Y., Gampierakis, I. A., Polissidis, A. et al. (2019) CRH promotes the neurogenic activity of neural stem cells in the adult hippocampus. Cell Reports, vol. 29, no. 4, pp. 932–945. https://doi.org/10.1016/j.celrep.2019.09.037 (In English)
Lu, J., Goula, D., Sousa, N., Almeida, O. F. X. (2003) Ionotropic and metabotropic glutamate receptor mediation of glucocorticoid-induced apoptosis in hippocampal cells and the neuroprotective role of synaptic N-methyl-D-aspartate receptors. Neuroscience, vol. 121, no. 1, pp. 123–131. https://doi.org/10.1016/s0306-4522(03)00421-4 (In English)
Mikhailenko, V. A., Butkevich, I. P., Vershinina, E. A. (2021) Studying the effect of neonatal inflammatory pain on cognitive processes and the reactivity of the hypothalamic-pituitary-adrenal system in rats of prepubertal age. Journal of Evolutionary Biochemistry and Physiology, vol. 57, no. 5, pp. 1031–1039. https://doi.org/10.1134/S0022093021050057 (In English)
Mogil, J. S. (2020) Qualitative sex differences in pain processing: Emerging evidence of a biased literature. Nature Reviewers Neuroscience, vol. 21, no. 7, pp. 353–365. https://doi.org/10.1038/s41583-020-0310-6 (In English)
Mooney-Leber, S. M., Brummelte, S. (2017) Neonatal pain and reduced maternal care: Early-life stressors interacting to impact brain and behavioral development. Neuroscience, vol. 342, pp. 21–36. https://doi.org/10.1016/j.neuroscience.2016.05.001 (In English)
Morris, R. G. M. (1981) Spatial localization does not require the presence of local cues. Learning and Motivation, vol. 12, no. 2, pp. 239–260. https://doi.org/10.1016/0023-9690(81)90020-5 (In English)
Nederhof, E., Schmidt, M. V. (2012) Mismatch or cumulative stress: Toward an integrated hypothesis of programming effects. Physiology and Behavior, vol. 106, no. 5, pp. 691–700. https://doi.org/10.1016/j.physbeh.2011.12.008 (In English)
Nelson, L. H., Lenz, K. H. (2017) The immune system as a novel regulator of sex differences in brain and behavioral development. Journal of Neuroscience Research, vol. 95, no. 1–2, pp. 447–461. https://doi.org/10.1002/jnr.23821 (In English)
Ranger, M., Grunau, R. E. (2014) Early repetitive pain in preterm infants in relation to the developing brain. Pain Management, vol. 4, no. 1, pp. 57–67. https://doi.org/10.2217/pmt.13.61 (In English)
Schwaller, F., Fitzgerald, M. (2014) The consequences of pain in early life: Injury-induced plasticity in developing pain pathways. European Journal of Neuroscience, vol. 39, no. 3, pp. 344–352. https://doi.org/10.1111/ejn.12414 (In English)
Sokołowski, A., Folkierska-Żukowska, M., Jednoróg, K. et al. (2020) The relationship between early and recent life stress and emotional expression processing: A functional connectivity study. Cognitive, Affective and Behavioral Neuroscience, vol. 20, no. 3, pp. 588–603. https://doi.org/10.3758/s13415-020-00789-2 (In English)
Timmers, I., Quaedflieg, C. W. E., Hsu, M. C. et al. (2019) The interaction between stress and chronic pain through the lens of threat learning. Neuroscience and Biobehavioral Review, vol. 107, pp. 641–655. https://doi.org/10.1016/j.neubiorev.2019.10.007 (In English)
Tjølsen, A., Berge, O.-G., Hunskaar, S. et al. (1992) The formalin test: An evaluation of the method. Pain, vol. 51, no. 1, pp. 5–17. https://doi.org/10.1016/0304-3959(92)90003-t (In English)
Ulrich-Lai, Y. M., Herman, J. P. (2009) Neural regulation of endocrine and autonomic stress responses. Nature Reviews. Neuroscience, vol. 10, no. 6, pp. 397–409. https://doi.org/10.1038/nrn2647 (In English)
Van Bodegom, M., Homberg, J. R., Henckens, M. J. A. G. (2017) Modulation of the hypothalamic-pituitary-adrenal axis by early life stress exposure. Frontiers in Cellular Neuroscience, vol. 11, article 87. https://doi.org/10.3389/fncel.2017.00087 (In English)
Verhaeghe, R., Gao, V., Morley-Fletcher, S. et al. (2021) Maternal stress programs a demasculinization of glutamatergic transmission in stress-related brain regions of aged rats. GeroScience, vol. 13, pp. 1–23. https://doi.org/10.1007/s11357-021-00375-5 (In English)
Victoria, N. C., Inoue, K., Young, L. J., Murphy, A. Z. (2013) Long-term dysregulation of brain corticotrophin and glucocorticoid receptors and stress reactivity by single early-life pain experience in male and female rats. Psychoneuroendocrinology, vol. 38, no. 12, pp. 3015–3028. https://doi.org/10.1016/j.psyneuen.2013.08.013 (In English)
Vorhees, C. V., Williams, M. T. (2014) Assessing spatial learning and memory in rodents. ILAR Journal, vol. 55, no. 2, pp. 310–332. https://doi.org/10.1093/ilar/ilu013 (In English)
Wang, K., Xu, F., Campbell, S. P. et al. (2020) Rapid actions of anti-Müllerian hormone in regulating synaptic transmission and long-term synaptic plasticity in the hippocampus. The FASEB Journal, vol. 34, no. 1, pp. 706–719. https://doi.org/10.1096/fj.201902217R (In English)
Xia, D., Min, C., Chen, Y. et al. (2020) Repetitive pain in neonatal male rats impairs hippocampus-dependent fear memory later in life. Frontiers in Neuroscience, vol. 14, article 722. https://doi.org/10.3389/fnins.2020.00722 (In English)
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