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Stopping Pain Without Affecting Motor Function

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Stopping Pain Without Affecting Motor Function

http://www.medicalnewstoday.com/articles/177925.php

One of the holy grails of local anesthesia is the ability to achieve a

long-lasting nerve block that eliminates pain sensation while not affecting

motor function. Now, researchers at Children's Hospital Boston have discovered

an anesthetic approach that seems to do just that. If it proves to work in

humans as well as it did in rats, it could be useful in a variety of medical

applications, providing, for example, a local anesthetic for childbirth that

would block pain without interfering with the mother's ability to push, or for

musculoskeletal disorders in which it is important to maintain mobility.

The discovery was reported in the online Early Edition of the Proceedings of the

National Academy of Sciences during the week of February 1.

The researchers, led by Kohane, MD, PhD, of the Division of Critical Care

Medicine at Children's, originally sought only to find an agent that would

prolong the anesthetics' effects. They focused on surfactants, a subclass of

so-called " chemical permeability enhancers " that enable drugs to spread more

easily throughout a tissue.

In testing three kinds of surfactant along with the anesthetics QX-314 and

QX-222 (both derivatives of lidocaine), they found that this approach did

prolong the sensory block in rats' sciatic nerves, for up to 7 hours or more

depending on the surfactant, but didn't prolong motor impairment; in some cases

the motor block was absent or of very short duration. In the rats, this meant

they were able to tolerate having their paws on a hot plate for long periods,

yet still able to balance and bear weight on their legs.

" This was a surprise finding, " says Kohane, who also directs the Laboratory for

Biomaterials and Drug Delivery (LBDD) at Children's. " What we've discovered

really is a new approach; the question now is to figure out the mechanism by

which it works and look at the effects of other chemical permeability

enhancers. "

Kohane speculates that surfactant made the anesthetic better able to penetrate

sensory nerves, which have little or none of the fatty coating known as myelin,

whereas in motor neurons, which have abundant myelin, the active drug gets

trapped in the myelin, never entering the nerve itself.

The lab's next steps will be to explore the effects of different permeability

enhancers and examine their safety, since at high doses the drug combination

could potentially be toxic to the nerves. The eventual plan is to test the

approach in larger animals.

A parallel approach to achieving a pain-specific nerve block was proposed in

2007 by Clifford Woolf, MD, PhD, recently appointed director of the Children's

Hospital Boston Program in Neurobiology. Woolf's team combined QXT-314 with

capsaicin, which opens cellular gates that are only present in sensory neurons,

and achieved pain-specific blocks in rats lasting 2 hours or more.

The new study was funded by the National Institutes of General Medical Sciences.

Itay Sagie, a research associate at the LBDD was the paper's first author. For

licensing information, see:

http://www.childrensinnovations.org/SearchDetails.aspx?id=1679.

Citation: Sagie I and Kohane D. Prolonged sensory-selective nerve blockade. PNAS

online early edition, week of February 1, 2010.

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