Pain in neonatal intensive care: Role of melatonin as an analgesic antioxidant

Endotracheal intubation is a common painful procedure in newborn care. Neonates are more sensitive to pain than older infants, children, and adults, and this hypersensitivity is further exacerbated in preterm neonates. The aim of this study was to evaluate the analgesic activity of melatonin during endotracheal intubation of the newborn by using the Neonatal Infant Pain Scale (NIPS) and Premature Infant Pain Profile (PIPP) score. Secondary outcome was an evaluation of melatonin as inflammatory responses. This was performed by measuring the levels of pro- and anti-inflammatory cytokines implicated in the pain. Sixty preterm infants were enrolled in the study and were randomly divided into two groups: 30 infants treated with melatonin plus common sedation and analgesia recommended by Italian Society of Neonatology (group 1) and 30 infants treated with only common sedation and analgesia. The sedative and analgesic drugs included atropine, fentanyl, and vecuronium. The reduction in pain score (NIPS) was similar in both groups at an early phase, while it (PIPP score) was lower in melatonin-treated group infants than the other newborns at a late phase, during intubation and mechanical ventilation. The differences were statistically significant at 12, 24, 48, and 72 hr (P < 0.001). Pro-inflammatory and anti-inflammatory cytokines (IL-6, IL-8, IL-10 and IL-12) were higher in the common sedation and analgesia group than in melatonin-treated infants at 24, 48, 72 hr and 7 days (P < 0.001). This study suggests the use of melatonin as an adjunct analgesic therapy during procedural pain, especially when an inflammatory component is involved.