Background Experimental studies have shown that neonatal exposure to stress, pain, opioids and anaesthetics
may cause histologic and morphologic changes in the central nervous system with associated functional
and behavioural changes in the long term. An important question is whether this holds true for humans also – and
in particular for sick neonates who often are exposed to pain and receive anaesthetics and sedatives.
Methods In this narrative review, we evaluate the effects of neonatal exposure to stress, pain, opioids and anaesthetics
in infancy and childhood in animals and in preterm born and term born humans on pain sensitivity, brain
morphology, cognition and behaviour later in life.
Results In animals, neonatal exposure to stress, pain, opioids and early exposure to anaesthetics are associated
with neurodegeneration and cognitive problems later in life. Human studies mainly focus on pain sensitivity,
cognition and behaviour and find contradictory outcomes. Dramatic long-term effects found in animal studies
could not be confirmed in human.
Conclusion While studies in animals suggest neurotoxic effects of early exposure to stress, pain, opioids and
anaesthetics, these effects seem clinically less relevant in humans. A possible reason is that the latter often receive
opioids in the presence of pain and opioids and anaesthetics in balanced therapeutic dosages and with adequate
monitoring of physiological parameters, in contrast to animal studies.