ArticleBrain : a journal of neurology2012
Priming of adult pain responses by neonatal pain experience: maintenance by central neuroimmune activity.
Article in Brain : a journal of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 223 citations in OpenAlex.
- Caregivers' perceptions, knowledge, and perceived barriers to pediatric procedural pain management: a cross-sectional study.Pain reports · 2026Article
- Repeated restraint stress-induced increase in post-surgical somatosensory hypersensitivity and affective responding is mediated by β-adrenergic receptor activation and spinal NLRP3-IL1β signalling in male rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Early Life Injury Alters Spinal Astrocyte Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Sex Differences in the Effects of Early Life Stressors in a Rat Model of Myofascial Low Back Pain.European journal of pain (London, England) · 2025Article
- PRG-1 Relieves Neonatal Stimuli-Induced Hyperalgesia and Anxiety via Stage-Specific Synapse Remodeling.CNS neuroscience & therapeutics · 2025Article
- Article
- Inflammation and macrophage infiltration exacerbate adult incision response by early life injury.BMC anesthesiology · 2025Article
- Article
- Latent bladder hypersensitivity induced by neonatal cystitis in rats unmasked by segmental but not hetero-segmental inflammation.Neuroscience letters · 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
- Early pain experiences in dairy calves on pain sensitivity later in life.JDS communications · 2024Article
- Deep learning to quantify care manipulation activities in neonatal intensive care units.NPJ digital medicine · 2024Article
- Macrophage memories of early-life injury drive neonatal nociceptive priming.Cell reports · 2024Article
- The Pharmacological Treatment of Neuropathic Pain in Children.Current neuropharmacology · 2024Review
- Developmental impact of peripheral injury on neuroimmune signaling.Brain, behavior, and immunity · 2023Review
- Repetitive and compulsive behavior after Early-Life-Pain associated with reduced long-chain sphingolipid species.Cell & bioscience · 2023Article
- Current Evidence for Biological Biomarkers and Mechanisms Underlying Acute to Chronic Pain Transition across the Pediatric Age Spectrum.Journal of clinical medicine · 2023Article
- Early-Life Iron Deficiency Persistently Alters Nociception in Developing Mice.The journal of pain · 2023Article
- Microglial phagocytosis mediates long-term restructuring of spinal GABAergic circuits following early life injury.Brain, behavior, and immunity · 2023Article
- New insights into irritable bowel syndrome pathophysiological mechanisms: contribution of epigenetics.Journal of gastroenterology · 2023Review
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Adult brain connectivity is shaped by the balance of sensory inputs in early life. In the case of pain pathways, it is less clear whether nociceptive inputs in infancy can have a lasting influence upon central pain processing and adult pain sensitivity. Here, we show that adult pain responses in the rat are 'primed' by tissue injury in the neonatal period. Rats that experience hind-paw incision injury at 3 days of age, display an increased magnitude and duration of hyperalgesia following incision in adulthood when compared with those with no early life pain experience. This priming of spinal reflex sensitivity was measured by both reductions in behavioural withdrawal thresholds and increased flexor muscle electromyographic responses to graded suprathreshold hind-paw stimuli in the 4 weeks following adult incision. Prior neonatal injury also 'primed' the spinal microglial response to adult injury, resulting in an increased intensity, spatial distribution and duration of ionized calcium-binding adaptor molecule-1-positive microglial reactivity in the dorsal horn. Intrathecal minocycline at the time of adult injury selectively prevented both the hyperalgesia and early microglial reactivity associated with prior neonatal injury. The enhanced neuroimmune response seen in neonatally primed animals could also be demonstrated in the absence of peripheral tissue injury by direct electrical stimulation of tibial nerve fibres, confirming that centrally mediated mechanisms contribute to these long-term effects. These data suggest that early life injury may predispose individuals to enhanced sensitivity to painful events.
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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.