Current Research

Last year, researchers led by David Julius and Jon Levine of the University of California, San Francisco (UCSF), cloned the capsaicin receptor--found exclusively in pain- processing neurons.⁹ When capsaicin binds to its receptor, it opens a channel and excites the neuron, which then transmits its pain signal. The same receptors are also located on neurons that are activated by heat--hence the burning sensation associated with a mouthful of hot chili peppers.

If researchers can figure out how to disable the capsaicin receptor, they might be able to stop pain messages before they start. Which is what UCSF colleagues have now done--using large doses of capsaicin itself. The researchers found that over stimulating the receptor can actually reduce clinical pain, perhaps by killing off the sensitive tips of these neurons by overexciting them.

But the capsaicin receptor is not the only exciting target molecule for potentially specific analgesics. Pain-sensing neurons also express a unique type of sodium channel. Sodium channels, in general, control the excitability of neurons all over the body--in the heart, the gut, and the nervous system. But the sodium channel found almost exclusively in small-diameter pain-sensing neurons--identified by John Wood and his colleagues at the University College of London and independently by John Hunter and his colleagues at Roche Bioscience in Palo Alto--is unusual in that it is resistant to tetrodotoxin (TTX), a neurotoxin from puffer fish that disables many other sodium channels.^10,11

The new TTX-resistant channel--dubbed PN3 by the Roche researchers--is definitely involved in transmitting and sensitizing animals to pain signals. They found that the channel accumulates at the point of injury.

Other pharmaceutical companies are now searching for inhibitors that will selectively block the activation of this TTX-resistant sodium channel, leaving the TTX-sensitive channels in the brain and heart and gut functioning normally.

In the meantime, PN3 has been joined by SNS2--a second TTX-resistant sodium channel--unlike PN3--is found exclusively in pain neurons.¹² The results look promising as we don't want to develop a drug that will block normal pain.