No 15/December 19, 2001
Embargoed until: Wednesday, December 19, 2001, 8 pm
DRASIC the Yin and Yang of Touch and Pain
Our senses of touch and pain, opposites one might think, have
something in common, an ion channel called DRASIC. DRASIC, which stands for
dorsal root ganglion acid sensitive channel, has just been shown to be critical
for both these senses as reported by a research group led by Gary Lewin at the
The DRASIC protein forms a channel in the membrane that when opened conducts sodium ions which then leads to the excitation of sensory neurons. One hypothesis is that mechanical forces on the membrane could open the channel: this would make it a mechanical sensor or ”mechanosensor”. More evidence for this idea comes from the fact that the channel is almost exclusively found in the sensory neurons of the dorsal root ganglia that are the first neurons in the pathways leading to the perception of touch and pain.
Lewin and colleagues looked at mice where the gene for DRASIC had been inactivated to see what sensory deficits they might exhibit. Surprisingly, in the absence of the DRASIC channel touch sensitive neurons had a much-increased sensitivity but pain-sensing neurons had a reduced sensitivity to mechanical stimulation of the skin (eg. pinch). Thus the same channel obviously helps sensory neurons to detect innocuous and painful stimuli in a completely different way. Therefore the mice might be better tuned to touch than they are to pinch!
The Lack of the Channel Protein had an Analgesic Effect
However, the multiple usefulness of this channel did not stop here. It was also known that this ion channel could also be opened by acid stimuli as well as by mechanical stimuli. Acid is a very important stimulus because acid is not only painful when we come into contact with it but injured tissues also becomes acidic (one reason why injury leads to a long lasting and unpleasant pain, sometimes called inflammatory pain). The pain sensing neurons that are sensitive to acid were recorded from in mice lacking the DRASIC channel and they where found to be much less sensitive to acid. Other behavioral experiments showed that when mice were challenged with an acidification of muscle (something that happens naturally after lots of strenuous exercise) they became very hypersensitive to touch (a correlate of the muscle ache and tenderness one feels after strong exercise or muscle injury). However, mice lacking DRASIC were much less affected by muscle acidification, in other words the lack of the channel protein had an analgesic effect. Obviously then DRASIC could be a very useful pharmacological target for the treatment of our aches and pains.
*The DRASIC Cation Channel
Contributes to the Detection of Cutaneous Touch and Acid Stimuli in Mice Margaret P. Price, Sabrina L. McIlwrath,
Jinhui Xie, Chun Cheng, Jing Qiao, Deirdre E. Tarr, Kathleen A. Sluka, Timothy
J. Brennan, Gary R. Lewin, Michael J. Welsh. Neuron
(Vol. 32, No 6, pp 1071 – 1083, December 19, 2001)
Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de
http://www.mdc-berlin.de/englisch/about_the_mdc/public_relations/e_index.htm
and
Dr. Gary Lewin
Robert Rössle Strasse 10
13125
Phone:+49/30/94 06 - 24 30/31 65
Fax: +49/30/94 06 - 27 93
e-mail: glewin@mdc-berlin.de