Early Neonatal Pain—A Review of Clinical and Experimental Implications on Painful Conditions Later in Life

Abstract

Modern health care has brought our society innumerable benefits but has also introduced the experience of pain very early in life. For example, it is now routine care for newborns to receive various injections or have blood drawn within 24 h of life. For infants who are sick or premature, the pain experiences inherent in the required medical care are frequent and often severe, with neonates requiring intensive care admission encountering approximately fourteen painful procedures daily in the hospital. Given that much of the world has seen a steady increase in preterm births for the last several decades, an evergrowing number of babies experience multiple painful events before even leaving the hospital. These noxious events occur during a critical period of neurodevelopment when the nervous system is very vulnerable due to immaturity and neuroplasticity. Here, we provide a narrative review of the literature pertaining to the idea that early life pain has significant long-term effects on neurosensory, cognition, behavior, pain processing, and health outcomes that persist into childhood and even adulthood. We refer to clinical and pre-clinical studies investigating how early life pain impacts acute pain later in life, focusing on animal model correlates that have been used to better understand this relationship. Current knowledge around the proposed underlying mechanisms responsible for the long-lasting consequences of neonatal pain, its neurobiological and behavioral effects, and its influence on later pain states are discussed. We conclude by highlighting that another important consequence of early life pain may be the impact it has on later chronic pain states-an area of research that has received little attention.

Time course of DNA methylation in pain conditions: From experimental models to humans

“…Growing evidence indicates that early-life stressors have implications for the vulnerability to develop painful conditions later in life (Waller et al, 2020). In line with these findings, it has been shown that premature babies exposed to many painful procedures present marked neurodevelopment changes in the nervous system (Williams & Lascelles, 2020). Since anxiety, depression, childhood trauma and adult stressful life events are associated with increased risk of developing chronic pain states (Abdallah & Geha, 2017;Bayram & Erol, 2014), it is plausible that this increased risk is based on 5mC alterations caused by external stressors (Niederberger et al, 2017).…”

Neurocritical care of premature infants

“…There are increasing concerns of what could be the consequences of early life pain and how is it going to affect the infants as they grow? A growing body of evidence reports long-term consequences of early life pain in humans show the association between early life pain and long-term neurosensory, cognitive, and psycho-behavioral disorders [ 70 , 71 ]. However, without methods to subjectively measure the degree of pain, and with current uncertainty of the effect of analgesics and sedatives exposure in the developing nervous system, assessment of pain and how to best alleviate it remains an important issue to be addressed in the critical care of preterm neonates.…”

Pain in full term newborns submitted to music and swaddling during venipunctures

“…Os recém-nascidos experienciam vários procedimentos dolorosos, ainda, nas 24 horas de vida, como parte da rotina de cuidados neonatal, como várias injeções e colheita de sangue (1) . A exposição constante do recém-nascido a esses procedimentos pode, em longo prazo, comprometer o desenvolvimento neurológico e comportamental, e as evidências mostram que o controle da dor acarreta benefícios nas respostas fisiológicas, comportamentais e hormonais desse recém-nascido.…”