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In NIH-funded work, they used specially designed fat-based particles called liposomes to package saxitoxin, a potent anesthetic, and produced long-lasting local anesthesia in rats without apparent toxicity to nerve or muscle cells. The research will be published online on April 13 by the Proceedings of the National Academy of Sciences.

"The idea was to have a single injection that could produce a nerve block lasting days, weeks, maybe even months," explains Daniel Kohane, MD, PhD, of the Division of Critical Care Medicine in the Department of Anesthesiology at Children's, and the report's senior author. "It would be useful for conditions like chronic pain where, rather than use narcotics, which are systemic and pose a risk of addiction, you could just put that piece of the body to sleep, so to speak."

In lab experiments, the researchers evaluated various formulations--various types of liposomes containing saxitoxin with or without dexamethasone, a potent steroid known to augment the action of encapsulated anesthetics. The best liposomes produced nerve blocks lasting two days if they contained saxitoxin alone and seven days if combined with dexamethasone.

Cell culture experiments and tissue analysis confirmed that the formulations were not toxic to muscle or nerve cells. Furthermore, when the team examined expression of four genes known to be associated with nerve injury, they found no up-regulation.

Kohane is currently optimizing the formulation to make it last even longer, while avoiding local and systemic toxicity. "It is conceivable we could have a formulation that is suitable for clinical trials before too long," he says.

The study was supported by the National Institute of General Medical Sciences. Hila Epstein-Barash, PhD, was first author on the paper.

To schedule an interview with Alison Cole, PhD, contact the NIGMS Office of Communications and Public Liaison at 301-496-7301 or info@nigms.nih.gov.

Contact:
Rob Graham
Children's Hospital Boston
617-919-3110
rob.graham@childrens.harvard.edu

Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 11 members of the Institute of Medicine and 12 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 397-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital and its research visit:www.childrenshospital.org/newsroom.