Anesthetic Approach Impedes Pain Without Affecting Motor Function

Sensory-selective local anesthesia, a key goal in local anesthetic development, could soon be an attainable reality, according to a new study.

Researchers at Children's Hospital Boston (MA, USA) who wished to find an agent that would prolong anesthetics' effects, decided to test three different kinds of surfactant in conjunction with the anesthetics QX-314 and QX-222, both derivatives of lidocaine. But while the researchers found that this approach did prolong the sensory block in rats' sciatic nerves--for up to 7 hours or more depending on the surfactant--it surprisingly did prolong motor impairment, and in some cases the motor block was absent or of very short duration. In the rat models, this meant that the animals were able to tolerate having their paws on a hot plate for long periods, yet still were able to balance and bear weight on their legs.

The researchers suggested that the observed effect was due to a local interaction between the surfactant and the lidocaine derivative, not a systemic effect. They thus speculated 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 actually entering the nerve itself. The next step will be to explore the effects of different permeability enhancers and examine their safety, since at high doses the anesthetic and surfactant combination could potentially be toxic to the nerves. The eventual plan is to test the approach in larger animals. The study was published early online on February 1, 2010, in the Proceedings of the National Academy of Sciences (PNAS).

"This was a surprise finding,” said Daniel Kohane, M.D., Ph.D., of the division of critical care medicine. "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.”

Myelin, an outgrowth of a glial cell, is a dielectric material that forms the myelin sheath, an insulating layer on the axon that is essential for the proper functioning of the nervous system. The main purpose of a myelin sheath is to increase the speed at which electrical impulses propagate; along unmyelinated fibers, impulses move continuously as waves, but in myelinated fibers, they hop or "propagate by saltation.” Myelin increases electrical resistance across the cell membrane by a factor of 5,000 and decreases capacitance by a factor of 50, thus preventing the electrical current from leaving the axon.

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