Too hot to handle! Scientists identify heat sensing regulator

The team then exposed one hind paw to capsaicin and found that mice lacking Pirt did not lick their paws as long as normal mice, suggesting that without Pirt, they were compromised in their ability to sense the spice of capsaicin. The researchers also tried mustard oil on the hind paw and found mice lacking Pirt licked for about the same amount of time as normal mice. These observations suggest that Pirt’s action is specific to capsaicin and not other chemicals.

To figure out whether Pirt directly affects TRPV1 channel action, the researchers measured electrical currents generated by TRPV1 in single nerve cells with or without Pirt. They exposed some nerves to noxious heat-108 degrees Fahrenheit-and some nerves to capsaicin and compared currents generated in each cell. Cells containing Pirt generated stronger currents in heat and spice than cells lacking Pirt, leading the researchers to conclude that Pirt is required for a full pain response to both heat and spice.

Further research revealed that Pirt interacts with yet another molecule in the cell, a so-called acidic phospholipid, allowing access to TRPV1. According to Dong, through this phospholipid Pirt somehow changes the TRP channel, perhaps by opening it wider, or maybe by causing it to stay open longer. And the result is elevated pain sensitivity.

Exactly how Pirt regulates the TRPV1 channel isn’t yet clear, says Dong. “The goal is to find molecules that specifically affect the pain pathway, but not other nerves,” he says. “We’re looking for genes specifically turned on in pain-sensing neurons. If we find them and can target them with new drugs, we will be able to treat pain without unfavorable side effects.”

The research was funded by the National Institute of Neurological Disorders and Stroke.

Authors on the paper are Andrew Y. Kim, Zongxiang Tang, Qin Liu, Kush N. Patel, David Maag, and Yixun Geng and Dong, all of Hopkins.

On the Web:
http://www.cell.com/
http://neuroscience.jhu.edu/