ReviewExperimental neurology2016
The long-term impact of early life pain on adult responses to anxiety and stress: Historical perspectives and empirical evidence.
Review in Experimental neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Associations of Mitochondrial Function, Stress, and Neurodevelopmental Outcomes in Early Life: A Systematic Review.Developmental neuroscience · 2022Pooled it
- Neonatal pain experience and pain sensitivity trajectories in preterm infants: A longitudinal study of flexion withdrawal reflex thresholds over the first two years of age.The journal of pain · 2025Article
- Early-life pain alters excitability of corticotropin-releasing factor-expressing neurons in the central amygdala and stress-induced hypersensitivity during adolescence.Frontiers in behavioral neuroscience · 2025Article
- The relationship between neonatal stress in preterm infants and developmental outcomes at the corrected age of 24-30 months.Frontiers in psychology · 2024Article
- Long-term effects of neonatal pain and sucrose treatment.Current research in pharmacology and drug discovery · 2024Article
- Article
- Infant pain vs. pain with parental suppression: Immediate and enduring impact on brain, pain and affect.PloS one · 2023Article
- Trauma-Informed Care in the Neonatal Intensive Care Unit: Through the Lens of the COVID-19 Pandemic.Cureus · 2022Review
- Signature for Pain Recovery IN Teens (SPRINT): protocol for a multisite prospective signature study in chronic musculoskeletal pain.BMJ open · 2022Article
- Assessment and Correction of Stress in Preterm Infants and Their Mothers.Turkish archives of pediatrics · 2022Article
- Developmental mechanisms of CPSP: Clinical observations and translational laboratory evaluations.Canadian journal of pain = Revue canadienne de la douleur · 2022Review
- Pain in Preterm Infants: Different Perspectives.The Journal of perinatal education · 2021Article
- Saccharin and naltrexone prevent increased pain sensitivity and impaired long-term memory induced by repetitive neonatal noxious stimulation: role of BDNF and enkephalin.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Early post-natal life stress induces permanent adrenocorticotropin-dependent hypercortisolism in male mice.Endocrine · 2021Article
- A Painful Beginning: Early Life Surgery Produces Long-Term Behavioral Disruption in the Rat.Frontiers in behavioral neuroscience · 2021Article
- 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 behavioral neuroscience · 2021Article
- Article
- Adrenal function links to early postnatal growth and blood pressure at age 6 in children born extremely preterm.Pediatric research · 2019Article
- Glucocorticoid receptor single nucleotide polymorphisms are associated with acute crisis pain in sickle cell disease.Pharmacogenomics · 2018Article
- Trauma-informed care in the newborn intensive care unit: promoting safety, security and connectedness.Journal of perinatology : official journal of the California Perinatal Association · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Approximately 1 in 6 infants are born prematurely each year. Typically, these infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they experience 10-18 painful and inflammatory procedures each day. Remarkably, pre-emptive analgesics and/or anesthesia are administered less than 25% of the time. Unalleviated pain during the perinatal period is associated with permanent decreases in pain sensitivity, blunted cortisol responses and high rates of neuropsychiatric disorders. To date, the mechanism(s) by which these long-term changes in stress and pain behavior occur, and whether such alterations can be prevented by appropriate analgesia at the time of insult, remains unclear. Work in our lab using a rodent model of early life pain suggests that inflammatory pain experienced on the day of birth blunts adult responses to stress- and pain-provoking stimuli, and dysregulates the hypothalamic pituitary adrenal (HPA) axis in part through a permanent upregulation in central endogenous opioid tone. This review focuses on the long-term impact of neonatal inflammatory pain on adult anxiety- and stress-related responses, and underlying neuroanatomical changes in the context of endogenous pain control and the HPA axis. These two systems are in a state of exaggerated developmental plasticity early in postnatal life, and work in concert to respond to noxious or aversive stimuli. We present empirical evidence from animal and clinical studies, and discuss historical perspectives underlying the lack of analgesia/anesthetic use for early life pain in the modern NICU.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.