{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T05:45:21Z","timestamp":1789796721872,"version":"4.0.1"},"reference-count":61,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T00:00:00Z","timestamp":1660867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81573171"],"award-info":[{"award-number":["81573171"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Neurobiology"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although extensive and untreated pain that occurs during a critical developmental window may impair cognition later in life, environmental interventions early in life might promote cognition. However, the underlying mechanism is poorly understood. Our current study utilized a rat model of \u201crepetitive needle pricks\u201d from the day of birth (P0) to postnatal day 7 (P7) to mimic the painful experience of preterm neonates in the neonatal intensive care unit. Enriched environment (EE) during development period (from P15 to P70) was implemented as a nonpharmacological intervention approach. Electrophysiological recording, behavioral tests, and biochemical analysis were performed after the end of EE (between P71 and P80). The results showed neonatal repetitive pain resulted in a reduction in mechanical withdrawal thresholds by the von Frey test in P70 (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001). Furthermore, neonatal repetitive pain impaired spatial learning and memory (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05) and even led to dysfunction in fear memory (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.01). In contrast, EE rescued neonatal pain\u2010induced cognitive deficits and normalized hippocampal long\u2010term potentiation in rats exposed to neonatal pain (<jats:italic>p<\/jats:italic> &lt;&lt;\u00a0.05). The beneficial effect of EE might be the improvements in hippocampal synaptic plasticity via upregulating neurotrophic factors and N\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate (NMDA) receptors in the hippocampus. Our findings provide evidence that early environmental intervention might be a safe strategy to overcome neurodevelopmental abnormalities in preterm infants who experienced multiple procedural painful events during the early critical period.<\/jats:p>","DOI":"10.1002\/dneu.22898","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T02:38:50Z","timestamp":1660099130000},"page":"545-561","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Enriched environment rescues neonatal pain induced cognitive deficits and the impaired hippocampal synaptic plasticity later in life"],"prefix":"10.1002","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6728-3680","authenticated-orcid":false,"given":"Cuiting","family":"Min","sequence":"first","affiliation":[{"name":"Department of Child Health Care Children's Hospital of Nanjing Medical University  Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Child Health Care Children's Hospital of Nanjing Medical University  Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Child Health Care Children's Hospital of Nanjing Medical University  Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongqing","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Child Health Care Children's Hospital of Nanjing Medical University  Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Child Health Care Children's Hospital of Nanjing Medical University  Nanjing P. R. 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