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University of Iowa News Release


Dec. 7, 2006

Nursing Researchers Find Genetic Link To Anesthetic Ineffectiveness

Researchers at the University of Iowa College of Nursing have identified an association between a gene variant and increased sensitivity to pain in some children, which may influence the effectiveness of topical anesthetics.

Charmaine Kleiber, Ph.D. (left), associate professor, and Debra Schutte, Ph.D. (right), assistant professor, are the lead authors on a paper to be published in an upcoming issue of The Journal of Pain.

In recent years, nurses and physicians have administered a lidocaine topical anesthetic, either EMLA or LMX4, to numb the skin prior to a needle stick. In a previous study, Kleiber had determined the two medications were equally effective.

"But it was interesting that, even with a small sample of 20 children, for some of them, neither medication was terrifically effective," Kleiber said.

She administered EMLA on one hand, and LMX4 on the other. In one instance, 10-year-old twin boys were in separate rooms, unaware of the other's procedure.

"Both complained of pain in both hands, with both products, which was odd," Kleiber said. That observation led her to suspect that genes could be a factor in the effectiveness of the medications.

As part of a four-year UI College of Nursing study of techniques used to distract children during painful procedures, in which Ann Marie McCarthy, Ph.D., professor, was principal investigator, the team studied 218 children ages 4 to 10 who were scheduled to undergo intravenous catheter insertion.

The researchers looked at several genes that influence pain pathways in various ways and singled out three genes that produce proteins that act in a location similar to where topical anesthesia acts: the endothelin 1 gene and its two receptors (endothelin receptors A and B).

"Based on what we knew about the biology of those genes, they were good candidates for this research question," Schutte said. "We hypothesized that if something is different in those genes, then the anesthetic may be less effective for that child."

The results of their study revealed that children who reported the high levels of pain were more likely to carry a particular genotype in the endothelin receptor A gene and also were significantly younger, more active and scored higher on anxiety measurement tests. Though children's temperament and activity level had been linked to pain response in prior studies, this is the first study that provides a genetic explanation.

"The more active, young and anxious a child is, the more likely the topical anesthetic won't have the best effect," Kleiber said. Since genotyping is not readily available in the everyday clinical setting, care providers may rely on these predictors (age, activity level and anxiety) to tailor pain-relieving strategies for children undergoing needle sticks.

The research team will incorporate these findings into evidence-based guidelines being developed for use in emergency rooms, along with information about the techniques used to distract children to lessen their discomfort during painful procedures.

In the meantime, Schutte said, "This is an analysis that definitely needs to be confirmed. The variant we were looking at with this gene wouldn't produce an obvious change in the gene product, so it's likely that some other sequence variant is one that plays a functional role in what we're seeing. It's not the end of the story."

McCarthy, Kleiber and Schutte hope to attract funding to examine the questions in a subsequent set of 500 children in order to confirm this association. 

According to Kleiber, the research underscores the importance of not promising a pain-free needle stick with topical anesthetic. "Clinically, we've seen that some children say it doesn't help," Kleiber said. "But often they're not believed by clinicians. Rather than giving false hope, what nurses can do is let children know the cream probably will help them feel less pain. We can tell them, 'Lots of children don't have much pain when we use this cream.'"

STORY SOURCE: University of Iowa College of Nursing, 101 Nursing Building, Iowa City, Iowa 52242

MEDIA CONTACT: Michele Francis, 319-335-8960,