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Why patients with epidermolysis bullosa suffer extreme pain
Date:7/8/2011

the cell in a controlled manner. Upon touch, pressure on the extracellular matrix actuates a tether mechanism on the ion channels, thus opening the channels and allowing the charged particles to flow through. This excites the neuron, thus enabling the stimulus to be perceived.

Unsuppressed mechanotransduction

In experiments using cell cultures, the MDC researchers found that physical stimuli trigger ion currents in all neurons not surrounded by laminin-332. In neurons growing on laminin-332, by contrast, the number of responsive cells was much reduced. "To a great extent, laminin-332 blocks the tether mechanism that opens the ion channels, thus impeding stimulus transduction. Because patients with epidermolysis bullosa are deficient in laminin-332, the transduction of the stimulus is unsuppressed. Their sensory neurons are excited much more strongly, and thus they react much more sensitively to mechanical stimuli," Professor Lewin explained.

Furthermore, in the skin tissue of EB patients the MDC researchers found that sensory neurons showed much more branching than in the skin of healthy individuals. "From cell-culture experiments we know that laminin-332 inhibits neuronal branching. Without laminin-332 this inhibition does not take place. Presumably, this effect also contributes to the increased perception of tactile stimuli," Professor Lewin said.

In further studies the researchers hope to find drug targets for therapy. However, much has already been achieved: "Because the causal mechanisms are now understood, we can focus on the patient's pain situation and on administering more efficient pain therapies," he added. "We recommend that in treating the disease, neurologists should be consulted in addition to dermatologists.


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Contact: bachtler@mdc-berlin.de
bachtler@mdc-berlin.de
49-309-406-3896
Helmholtz Association of German Research Centres
Source:Eurekalert

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