The painful truth: Babies born prematurely don’t adapt to pain the way other babies do

Resume: Babies born prematurely do not get used to repeated pain in the same way that full-term babies or adults do. Researchers believe this is because premature babies have not yet developed the mechanism that allows humans to adapt to moderate pain, which is believed to develop during the third trimester of pregnancy.

Source: UCL

Premature babies don’t get used to repeated pain the way full-term babies, children and adults get used to pain, according to a study led by UCL (University College London) researchers.

The authors of the new Current Biology paper say that if premature babies haven’t yet developed the mechanism that allows people to get used to moderate pain, medical procedures in their first few weeks of life could potentially affect their development.

Lead author Dr. Lorenzo Fabrizi (UCL Neuroscience, Physiology & Pharmacology) said: “The way we can get used to things can be seen as the simplest example of behavioral and brain plasticity, and it is a fundamental part of memory and learning.

“Pain habituation is important because it allows us to conserve physical, emotional and cognitive resources by not overreacting to pain that is unavoidable or not life-threatening.

“Our findings suggest that the ability to get used to repeated pain might develop during the third trimester of pregnancy, so preterm infants have not yet developed this ability that full-term infants have from birth.”

The study involved 20 babies at University College London Hospitals (UCLH). Half of them were born prematurely (and tested while still under 35 weeks gestation*), while the other half were born full term (seven babies) or born prematurely but tested at full term (three babies).

The two groups were similar in their actual postnatal age, as the preterm infants had a median age of 14 days, compared to 10 days in the term (or term) group.

The researchers measured the babies’ responses to a painful but clinically required heel lance (blood test), which was performed twice (three to 18 minutes apart) for each baby (two lances are sometimes needed to collect enough blood; this is not needed for most babies, so only those who needed a second lance were included in the study).

Heel lances can elicit significant pain responses in infants, but it was not previously known whether this decreases with repeated lances. To understand this, the researchers recorded the babies’ brain activity with EEG (electroencephalography) electrodes placed on the scalp, and their heartbeats using EKG (electrocardiography), while also recording their facial expressions and reflexes on retraction. guarding the leg.

The researchers found that brain activity immediately after the second heel lance was not as strong as after the first, suggesting a habituation response, but this was only the case in full-term babies.

They add that habituation to pain could protect full-term babies, but not those born prematurely, from potential developmental consequences. The image is in the public domain

They found a similar pattern for heart rate and facial expressions, as preterm infants responded just as strongly to both heel lances, while the full-term infants seemed to get used to the pain.

The team says this habituation response may be due to the full-term babies anticipating the imminent pain when they receive a second heel lance, so their response is less pronounced, or it may be instead or additionally due to the fact that their brain modulates their reflexive survival responses. .

They add that habituation to pain could protect full-term babies, but not those born prematurely, from potential developmental consequences.

First author Dr Mohammed Rupawala (UCL Neuroscience, Physiology & Pharmacology) said: “Although unpleasant and painful clinical procedures are necessary for many young babies, there is the possibility that they may affect their development, for example through altered pain perception or possibly decreased gray matter. or disturbed white matter in the brain.”

Co-author Dr Judith Meek, neonatologist consultant at UCLH, said: “This work raises awareness of the additional vulnerability of preterm infants to pain. Clinicians should do their best to protect them from repeated painful experiences. This should be considered an essential part of brain-centered care for newborns.”

The study, funded by the Medical Research Council and the European Research Council, involved researchers from UCL, UCLH and York University (Canada).

* Gestational age refers to the number of weeks that have passed since the start of the mother’s last menstrual cycle. The 10 babies classified as preterm in this study had a median gestational age of 31 weeks, so they were still in developmental stages normally experienced while still in the womb.

About this news about neurological development and pain research

Author: Chris Lane
Source: UCL
Contact: Chris Lane – UCL
Image: The image is in the public domain

Original research: Open access.
“A developmental shift in habituation to human neonatal pain” by Lorenzo Fabrizi et al. Current Biology


A developmental shift in habituation to pain in human newborns


  • Full-term but not premature newborns get used to repeated unavoidable painful stimuli
  • Habituation occurs in behavioral, autonomic, and early cortical responses
  • Higher level pain processing is influenced by stimulus repetition in both age groups


Habituation to recurrent non-threatening or unavoidable noxious stimuli is an important aspect of adaptation to pain.

Neonates, especially those born prematurely, are repeatedly exposed to harmful procedures during their clinical care. They can elicit strong behavioral, autonomic, spinal, and cortical responses to a single noxious stimulus; however, it is unknown whether the developing nervous system can adapt to the repetition of these inputs.

Here we used electroencephalography to examine changes in cortical microstates (representing the complex sequential processing of noxious inputs) following two consecutive clinically required heel lances in term and preterm infants.

We show that stimulus repetition dampens the involvement of initial microstates and associated behavioral and autonomic responses in term infants, while preterm infants show no signs of habituation.

Nevertheless, both groups use different cortical microstates with longer latency for each lance, likely reflecting changes in higher-level stimulus processing with repeated stimulation.

These data suggest that while both age groups are able to encode contextual differences in pain, the preterm brain does not regulate initial cortical, behavioral and autonomic responses to repeated noxious stimuli.

Mechanisms of habituation to pain are already present at term, but mature during the equivalent of the last trimester of pregnancy and are not fully functional in preterm neonates.

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