ArticlePloS one2013
Postnatal temporal, spatial and modality tuning of nociceptive cutaneous flexion reflexes in human infants.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 76 citations in OpenAlex.
- Pharmacological interventions for the prevention of pain during endotracheal suctioning in ventilated neonates.The Cochrane database of systematic reviews · 2025Pooled it
- Non-pharmacological interventions for the prevention of pain during endotracheal suctioning in ventilated neonates.The Cochrane database of systematic reviews · 2024Pooled it
- Encoding of mechanical nociception differs in the adult and infant brain.Scientific reports · 2016Trial
- Article
- Muscle responses to limb block during spontaneous movements in infants.Frontiers in neuroscience · 2025Article
- Establishing a standardised approach for the measurement of neonatal noxious-evoked brain activity in response to an acute somatic nociceptive heel lance stimulus.Cortex; a journal devoted to the study of the nervous system and behavior · 2024Article
- Sensory event-related potential morphology predicts age in premature infants.Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 2024Article
- Article
- The fetal pain paradox.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Article
- Premature infants display discriminable behavioral, physiological, and brain responses to noxious and nonnoxious stimuli.Cerebral cortex (New York, N.Y. : 1991) · 2022Article
- The development of descending serotonergic modulation of the spinal nociceptive network: a life span perspective.Pediatric research · 2022Review
- Article
- Tactile sensitivity and motor coordination in infancy: Effect of age, prior surgery, anaesthesia & critical illness.PloS one · 2022Article
- Accurate classification of pain experiences using wearable electroencephalography in adolescents with and without chronic musculoskeletal pain.Frontiers in pain research (Lausanne, Switzerland) · 2022Article
- Modified Sensory Testing in Non-verbal Patients Receiving Novel Intrathecal Therapies for Neurological Disorders.Frontiers in neurology · 2022Article
- Toward personalized medicine for pharmacological interventions in neonates using vital signs.Paediatric & neonatal pain · 2021Review
- Quantifying noxious-evoked baseline sensitivity in neonates to optimise analgesic trials.eLife · 2021Observational
- The development of pain circuits and unique effects of neonatal injury.Journal of neural transmission (Vienna, Austria : 1996) · 2020Review
- Multimodal pain assessment improves discrimination between noxious and non-noxious stimuli in infants.Paediatric & neonatal pain · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Cutaneous flexion reflexes are amongst the first behavioural responses to develop and are essential for the protection and survival of the newborn organism. Despite this, there has been no detailed, quantitative study of their maturation in human neonates. Here we use surface electromyographic (EMG) recording of biceps femoris activity in preterm (<37 weeks gestation, GA) and term (≥ 37 weeks GA) human infants, less than 14 days old, in response to tactile, punctate and clinically required skin-breaking lance stimulation of the heel. We show that all infants display a robust and long duration flexion reflex (>4 seconds) to a single noxious skin lance which decreases significantly with gestational age. This reflex is not restricted to the stimulated limb: heel lance evokes equal ipsilateral and contralateral reflexes in preterm and term infants. We further show that infant flexion withdrawal reflexes are not always nociceptive specific: in 29% of preterm infants, tactile stimulation evokes EMG activity that is indistinguishable from noxious stimulation. In 40% of term infants, tactile responses are also present but significantly smaller than nociceptive reflexes. Infant flexion reflexes are also evoked by application of calibrated punctate von Frey hairs (vFh), 0.8-17.2 g, to the heel. Von Frey hair thresholds increase significantly with gestational age and the magnitude of vFh evoked reflexes are significantly greater in preterm than term infants. Furthermore flexion reflexes in both groups are sensitized by repeated vFh stimulation. Thus human infant flexion reflexes differ in temporal, modality and spatial characteristics from those in adults. Reflex magnitude and tactile sensitivity decreases and nociceptive specificity and spatial organisation increases with gestational age. Strong, relatively non-specific, reflex sensitivity in early life may be important for driving postnatal activity dependent maturation of targeted spinal cord sensory circuits.
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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.