The consequences of neonatal pain, stress and opiate administration in animal models: An extensive meta-analysis concerning neuronal cell death, motor and behavioral outcomes

Abstract

This systematic review and meta-analysis aimed to investigate the association of neonatal exposure to pain, stress, opiate administration alone, as well as opiate administration prior to a painful procedure on neuronal cell death, motor, and behavioral outcomes in rodents. In total, 36 studies investigating the effect of pain (n = 18), stress (n = 15), opiate administration (n = 13), as well as opiate administration prior to a painful event (n = 7) in rodents were included in our meta-analysis. The results showed a large effect of pain (g = 1.37, 95% CI 1.00-1.74, p < .001) on neuronal cell death. Moreover, higher number of neonatal pain events were significantly associated with increased neuronal cell death, increased anxiety (b = -1.18, SE = 0.43, p = .006), and depressant-like behavior (b = 1.74, SE = 0.51, p = .027) in rodents. Both opiates and pain had no impact on motor function (g = 0.26, 95% CI 0.18-0.70, p = .248).

Keywords: Apoptosis; Behavioral outcome; Meta-analysis; Morphine; Motor outcome; Neonatal pain; Neonatal sedation; Preterm infants.