The Wonders of Ion Channels
In 1997 David Julius and his team determined how capsaicin was involved in our registration of "heat" from chillies. Most of our sensory system is based on ion channels opening up suddenly, allowing ions to influx into a cell and generate an electrical signal. Using genetics the exact channel was identified by julius, the TRPV1 channel. More crucially though he illustrated how that same channel also reacts to heat changes, responding to uncomfortably high temperatures like 43 degrees Celcius which would damage the tissues in a human mouth. This helps to explain why chillis feel like they are "burning". In 2002 he also discovered TRMP8, the channel activated by cooler temperatures, 10-30 degrees Celcius. This channel is interestingly triggered by Menthol, helping to explain its "cool" sensation.
Here is where it gets very interesting. Julius and his colleagues then created a strain of genetically engineered mouse with defective copies of the gene that coded for its protein. He then created two chambers, one at 15 and the other at 30 degrees Celcius and placed both unaltered and the modified mice into the system. Naturally the unaltered mice moved to the 30 degree celcius chamber whilst the modified mice were fine in either temperature and appeared to not be too bothered.
So how does this help humans?
Well the receptors are also linked to pain and so drug develpoers were naturally interested, they invested £60million into developing these drugs but it was later found that they dangerously also removed sensation of high temperature leading to burns and other injuries as a result of no temperature sensation. However they have now found that a protein called AKAP79 is responsible for making the TRPV1 channel more "sensitive". "It localises some of the components of signalling pathways to the right regions inside the cell, so that they're ready to go when the pathway is switched on," says Joan Btesh
The key therefore was to prevent the two from binding and Peter McNaughton has done just that, he claims that preventing the two combining reducing the pain associated with inflammation whilst also keeping the pain sensation of heat, it does this by not allowing the cells to be modified.
Furthermore it is being targetted for use in local dental analgesias as Capsaicin can be used to open the ion channels, followed by drugs that affect the cells of the pain receptors directly, not affecting the muscles and leaving you a drooling mess at "rinse please"
TRPM8 was also shown to appear in higher levels in prostate cancer tumours and the more severe they were, the more TRPM8 was found in them. These ion channels have long since been linked with the formation of cancers and TRPM8 receptors can also been found in the walls of blood vessels helping to explain the transmission of tumours around the body. If indeed, blocking or reducing the amount of TRPM8 could reduced the size, stop the growth or even remove these tumors completely, a drug could be found to inhibit their binding. How cool would that be? (hats off to those who got that)