Procedural pain and oxidative stress in premature neonates

J Pain. 2012 Jun;13(6):590-7. doi: 10.1016/j.jpain.2012.03.010. Epub 2012 Apr 28.


Preterm neonates exposed to painful procedures in the neonatal intensive care unit exhibit increased pain scores and alterations in oxygenation and heart rate. It is unclear whether these physiological responses increase the risk of oxidative stress. Using a prospective study design, we examined the relationship between a tissue-damaging procedure (TDP; tape removal during discontinuation of an indwelling central arterial or venous catheter) and oxidative stress in 80 preterm neonates. Oxidative stress was quantified by measuring uric acid (UA) and malondialdehyde (MDA) concentration in plasma before and after neonates (n = 38) experienced a TDP compared to those not experiencing any TDP (control group, n = 42). Pain was measured before and during the TDP using the Premature Infant Pain Profile (PIPP). We found that pain scores were higher in the TDP group compared to the control group (median scores, 11 and 5, respectively; P < .001). UA significantly decreased over time in control neonates but remained stable in TDP neonates (132.76 to 123.23 μM versus 140.50 to 138.9 μM; P = .002). MDA levels decreased over time in control neonates but increased in TDP neonates (2.07 to 1.81 μM versus 2.07 to 2.21 μM, P = .01). We found significant positive correlations between PIPP scores and MDA. Our data suggest a significant relationship between procedural pain and oxidative stress in preterm neonates.

Perspective: This article presents data describing a significant relationship between physiological markers of neonatal pain and oxidative stress. The method described in this paper can potentially be used to assess the direct cellular effects of procedural pain as well the effectiveness of interventions performed to decrease pain.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Humans
  • Infant, Newborn
  • Infant, Premature / physiology*
  • Malondialdehyde / blood
  • Oxidative Stress / physiology*
  • Pain / complications*
  • Pain Measurement
  • Uric Acid / blood


  • Uric Acid
  • Malondialdehyde