How the developing brain experiences pain

When a newborn cries during a blood test or vaccination, it's heartbreaking. Parents and doctors alike know that babies feel pain, but there's an important difference: their brains don't process it in the same way adults' brains do. A new study published in PAIN offers a closer look inside the infant brain, showing how the networks involved in pain perception develop on different timelines during early life.

The research, conducted by a team from University College London and King's College London, used advanced brain imaging to track how the pain-processing circuits of newborns develop during the final trimester of pregnancy. The findings suggest that while babies can register pain, the emotional and interpretive aspects of the experience, the “this feels awful” and “what does this mean?” components, emerge later.

But first, it's important to realize that pain is more than just a sensation. Pain is often thought of as a single feeling: sharp, dull, burning, throbbing. Neuroscience, however, breaks it down into three closely linked components: sensory-discriminative, that is, where the pain is and how intense it is; affective-motivational, or how unpleasant or distressing it feels; and cognitive-evaluative, representing how the brain interprets the pain and its significance.

Together, these elements form what researchers call the pain connectome, a network of brain regions that work together during painful experiences. In adults, this network spans sensory regions, emotional centers such as the amygdala, and higher-order areas in the prefrontal cortex.

When this network takes shape during development has long been an open question, and that's exactly the one the team aimed to address. To answer it, the researchers drew on two large brain-imaging datasets. One was the Developing Human Connectome Project, which includes hundreds of MRI scans from infants scanned while asleep, some as early as 26 weeks post-conception. The other was the Human Connectome Project, a well-established dataset of healthy young adults.

By comparing 372 infant scans with 98 adult scans, the team mapped how the pain connectome evolves during the final weeks of pregnancy. Rather than exposing infants to painful stimuli—an obvious ethical barrier, the researchers analyzed resting-state brain activity, examining how different regions naturally communicate when the brain is at rest.

A clear developmental sequence emerged. Before 32 weeks, brain connections related to pain are sparse and poorly organized, far from resembling the adult pattern. In the period between 34–36 weeks, the sensory component of the network—the circuits that detect physical stimuli—reaches adult-like levels. Between week 36 and 38, the emotional component begins to mature, enabling distress and aversion responses to pain. At term (40 weeks), the cognitive component remains underdeveloped, meaning full-term newborns still lack adult-like interpretation of pain.

The researchers also found that some sensory connections in late-term infants were stronger than those seen in adults. This reflects a common feature of early brain development, where connections are initially abundant before being refined through pruning.

These findings refine our understanding of how infants experience medical procedures. A premature baby in a neonatal intensive care unit may clearly react to a heel prick or blood draw—grimacing, withdrawing, crying. According to this research, however, those reactions are driven primarily by sensory input rather than by fully developed emotional or cognitive processing.

Importantly, this does not mean infant pain is insignificant. The authors emphasize that immature networks may actually increase vulnerability. Early painful experiences, if not properly managed, could influence how sensory pathways develop, with potential long-term consequences.

The findings align closely with everyday clinical experience. Premature infants often undergo repeated procedures, making careful pain management and gentle handling especially critical. It's important to understand how early brain development shapes later outcomes and connect advanced imaging techniques with practical questions about neonatal care and long-term neurodevelopment.

This research can impact medical care, where pain management for newborns should account for developmental differences rather than relying on adult models. Also, it's important for reassuring parents: while babies do feel pain, their brains do not yet attach the same emotional or cognitive weight to it as adults do.

This research highlights pain as a developmental process rather than a fixed experience. Sensory detection appears first, emotional response follows, and higher-level interpretation develops later. The cry of a newborn in response to a needle is real and deserving of compassion, but it arises from a brain that is still under construction. So, the experience is not identical to adult pain, even if it looks similar on the surface.

If you want to learn more, read the original article titled "Differential maturation of the brain networks required for the sensory, emotional, and cognitive aspects of pain in human newborns" on Pain at http://dx.doi.org/10.1097/j.pain.0000000000003619.