Sweet relief or lasting impacts? Review of neonatal pain and sucrose in developing rodents

In the neonatal intensive care unit, preterm infants can experience 7 to 17 painful and stressful procedures daily. Oral sucrose is the standard treatment for procedural pain, but their combined short-term and long-term cumulative effects on brain development remain unclear. Growing concerns about the potential neurodevelopmental consequences of repeated sucrose and pain exposure underscore the need for mechanistic research to understand their interaction during critical periods of brain development. Translational animal models, particularly in rodents, are instrumental in advancing neonatal pain research. Their comparable neurodevelopmental trajectory to human infants and the ability to systematically control pain and sucrose exposures make them valuable tools for investigating both immediate and enduring effects. These models have been refined to replicate clinically relevant procedural pain in the neonatal intensive care unit and have yielded mixed findings. Some studies report that sucrose reduces short-term pain sensitivity and improves early spatial learning, whereas others show impaired short-term memory and long-term reductions in regional brain and white matter volumes. This review synthesizes current literature on translational rodent models of early-life pain and sucrose exposure, highlighting both potential benefits and adverse outcomes. These findings underscore the complexity of using sucrose as an analgesic and the importance of ongoing preclinical research to inform evidence-based neonatal pain management. By critically evaluating the dual impact of pain and sucrose, this work contributes to a deeper understanding of how early interventions shape neurodevelopment and supports the development of safer, more effective strategies for managing pain in this vulnerable population.