A groundbreaking study led by researchers at University College London (UCL) has illuminated the complex and staggered development of brain networks responsible for processing pain in human newborns. This research, published in the prestigious journal Pain, reveals that the neural pathways underlying the sensory, emotional, and cognitive experiences of pain mature at markedly different rates throughout early infancy. Employing cutting-edge magnetic resonance imaging (MRI) techniques, the study sheds fresh light on how premature and full-term infants perceive pain, providing crucial insights that may reshape neonatal medical care and pain management protocols.
The intricate experience of pain incorporates multiple dimensions, including sensory discrimination — the ability to identify and locate painful stimuli — affective motivation, which governs the emotional response to pain, and cognitive evaluation, reflecting the brain’s capacity to interpret and understand pain. In adults, these processes engage a widely distributed network of brain regions collectively known as the “pain connectome,” each region contributing distinct functional roles. Until now, however, the developmental timelines of these interconnected networks in newborns, especially those born prematurely, remained poorly understood.
Using data derived from the Developing Human Connectome Project alongside the Human Connectome Project — among the largest repositories of infant and adult brain MRI scans globally — the research team mapped functional connectivity within the brains of 372 infants scanned within their first two weeks of life. Most infants were born prematurely (before 32 weeks gestation), allowing investigators to disentangle brain maturation effects intrinsic to fetal development from environmental influences encountered after birth. This approach enabled a refined view of how different pain-processing circuits emerge in early brain development.
Their analysis revealed that the sensory-discriminative brain network, responsible for detecting and localizing pain, is the first to reach levels comparable to those observed in mature adults. This maturation occurs between approximately 34 and 36 weeks after conception, suggesting that even very premature infants gain a biological capacity to sense pain specifically. However, prior to this developmental milestone, infants may experience difficulty pinpointing the exact location or intensity of painful stimuli, highlighting a limited sensory awareness at earlier gestational ages.
Following the maturation of sensory-discriminative circuits, the affective-motivational subnetwork matures around 36 to 38 weeks after conception. This network underpins the emotional and motivational dimensions of pain, including recognizing pain as unpleasant and threatening. Thus, by the later stages of gestation, infants begin to develop an emotional response to pain, although the quality and complexity of these feelings are likely distinct from those of adults. Interestingly, the functional strength and connectivity of this affective-motivational circuit indicate a progressive enhancement of the infant’s capacity to process the unpleasantness of painful stimuli.
Strikingly, the cognitive-evaluative network, essential for the appraisal and interpretation of pain, demonstrates a much later developmental trajectory. The study finds that this network remains immature beyond 42 weeks post-conception, meaning that even full-term newborns have not yet developed the brain infrastructure necessary for conscious understanding or nuanced appraisal of pain. This delayed maturation may explain why behavioral and physiological responses to pain in newborns differ significantly from those in older children and adults, who can contextualize pain within broader cognitive frameworks.
This staggered maturation of pain-processing networks has profound implications, especially regarding the vulnerability of premature infants to painful medical procedures. Previous investigations by the same team in 2023 reported that premature babies exhibit a lack of habituation — a decreased response — to repeated painful stimuli during essential medical interventions. The current findings offer a plausible neurological basis for this phenomenon, revealing that underdeveloped brain networks hinder the infant’s ability to cognitively evaluate and potentially modulate pain perception over time.
Professor Lorenzo Fabrizi, the study’s lead author and a specialist in Neuroscience, Physiology, and Pharmacology at UCL, emphasizes the clinical significance of these findings. He explains that “preterm babies may be particularly susceptible to the deleterious effects of pain during key phases of brain development,” underscoring an urgent need for pediatric care strategies that tailor pain management to the unique neurodevelopmental state of newborns. This could involve the judicious timing of interventions and individualized analgesia plans to mitigate the potential long-term impacts of neonatal pain.
The research methodology stands out due to its utilization of large-scale high-resolution MRI datasets combined with advanced analytic techniques to construct functional connectivity maps of infant brains. By comparing these connectivity patterns to well-characterized adult pain networks, the study offers a rare, longitudinal perspective on neurodevelopment that bridges the gap between preterm and full-term brain maturation. This approach sets a new standard for developmental neuroscience research, leveraging big data to unravel complex, dynamic brain processes in early life.
Beyond its immediate clinical relevance, the study opens avenues for exploring how disrupted or delayed maturation of pain networks might contribute to neurodevelopmental disorders later in life. Since pain processing involves multiple overlapping brain regions also implicated in emotional regulation, cognition, and sensory integration, aberrations in these pathways during critical windows of brain growth could have cascading effects. Future research may investigate whether early interventions can foster healthier network development, potentially reducing risks of chronic pain conditions or affective disorders.
Moreover, this study challenges historically oversimplified views that newborns experience pain similarly to adults. The nuanced delineation of sensory versus emotional and cognitive components highlights that the newborn pain experience is qualitatively distinct and relatively primitive. This understanding invites a re-examination of neonatal pain assessment protocols, moving beyond behavioral indicators alone toward incorporating neurophysiological markers that reflect network maturation and function more directly.
The ethical ramifications are also substantial, calling for heightened sensitivity to pain in neonatal care, especially among preterm infants who undergo multiple unavoidable medical procedures. As the authors note, comprehending the neurobiological underpinnings of neonatal pain not only advances scientific knowledge but also reinforces the moral imperative to develop pain-relief methods that respect the developing infant brain’s unique vulnerabilities.
Funded by the Medical Research Council, this study exemplifies the cutting-edge fusion of developmental biology, neuroimaging technology, and clinical neuroscience. By charting the differential maturation of the brain’s pain connectome, it lays crucial groundwork for redefining pain management in newborns and offers hope for enhancing both immediate outcomes and long-term neurological health.
Subject of Research: People
Article Title: Differential maturation of the brain networks required for the sensory, emotional, and cognitive aspects of pain in human newborns
News Publication Date: 18-Jun-2025
Web References:
10.1097/j.pain.0000000000003619
References:
Published in Pain journal
Keywords:
Pain, Affective pain, Infants, Developmental neuroscience, Brain development, Cognitive development, Neuroscience
