A Loma Linda University School of Medicine researcher is seeking to reduce pain for premature babies.

Danilyn Angeles, PhD, is passionate about babies. After working as a nurse on the neonatal intensive care unit (NICU) at Loma Linda University Children’s Hospital for 20 years, Angeles returned to school, got her doctorate in physiology, and launched a research career. Today, whether educating medical students, nurses, and physicians on the importance of pain reduction or seeking better treatment methods in the laboratory, she is always trying to make life better for babies.

Right now, Angeles is midway through a $1.6 million National Institutes of Health R01 study titled “Non-pharmacological interventions for procedural pain in premature infants.” The study aims to determine which of three pain-relief methods will produce the least amount of pain and lowest incidence of trauma, stress, and systemic cell injury in babies.

The three methods Angeles is testing involve combining an oral analgesic with non-nutritive sucking (NNS) and facilitated tucking. NNS is fancy nomenclature for letting babies suck on a pacifier; facilitated tucking describes a way of holding their arms and legs in a flexed position near the midline of the torso. 

Angeles says that while currently unavoidable, the pain caused by necessary medical procedures has proven to be harmful to infants.

“Some people think babies don’t feel pain,” she acknowledges, “or that it only affects them for a moment, but that just isn’t true. In the NICU, babies can be subjected to multiple painful procedures every single day, and what we’re finding is that it can cause significant problems for them.”

Angeles says painful infant medical procedures cause:

  • Physiologic instability
  • Impairment in pain response
  • Decreased or blunted sensitivity to subsequent painful procedures
  • Abnormal brain development, and
  • Altered stress response systems which can persist into childhood.

“There is also mounting evidence that pain and stress in babies correlate with neuropsychiatric disorders such as anxiety, depression, and addiction in adulthood,” she warns.

In an article published in the February 18, 2013, edition of The Journal of Pediatrics, Angeles and her colleagues—Elba Fayard, MD, Danilo Boskovic, PhD, Douglas Deming, MD, Megan Holden, PhD, Laurel Slater, and Yayesh Asmerom, MS—shared the findings of an earlier study in which they found that the use of oral sucrose while a heel lance was performed to obtain a blood sample reduced the infant’s subjective experience of pain.

Unfortunately, the use of oral sucrose—commonly administered as the commercial product Sweet-Ease—also increased ATP degradation. The acronym stands for adenosine triphosphate which, when it breaks down, signals tissue hypoxia and several other stressors that can damage an infant’s cells and deplete the energy available to them for the performance of vital developmental functions.

“These findings lead to the question,” Angeles observed, “if oral sucrose does not effectively reduce the biochemical effects of procedural pain, what intervention or groups of interventions will decrease both behavioral markers of pain and markers of ATP degradation, oxidative stress and cell injury?”

To find out, she and her team launched preliminary investigations, which yielded three significant findings:

  • Exposure to a single painful procedure—such as a heel lance or even the rapid removal of tape from a baby’s skin—causes pain and may trigger ATP degradation and reduce a neonate’s modest energy stores
  • The use of oral sucrose significantly increases the markers for oxidative stress
  • Painful procedures contribute to cell injury in pre-term infants.

Since sucrose triggers ATP degradation, Angeles and her colleagues are now testing a related sugar to see if it might reduce pain without the unwanted side effects.

“There is a metabolic cost to the use of oral sucrose,” she explains, “which may be due to the fructose moiety. It is ATP degradation, or energy depletion. Signs of pain may decrease, but at the cost of ATP or energy. This is why an alternative treatment is needed and why we are testing the effect of 30% dextrose (or D-glucose) with or without facilitated tucking.”

Final results of the four-year study won’t be available until 2018, but Angeles says the sucrose alternative is doing very well so far: it now appears that any of the three alternative methods can be used instead of sucrose, with better results.

“The knowledge that will be gained from this study will have significant impact on the clinical care of premature patients admitted to the NICU,” she concludes. “Our findings will provide evidence-based interventions that clinicians can utilize to relieve pain in neonates without depleting the neonate’s already reduced energy stores.”

And that, she affirms, will be very good for babies.