Three years ago, Iadarola's group published data showing the RTX-induced flow of calcium can overdose, seriously disable, and ultimately kill these neurons. Because nerve cells in the peripheral nervous system first transmit their signals to the spine, where they then are processed and routed onward to the brain, their previous finding raised an intriguing therapeutic scenario: The cell bodies of these peripheral neurons bundle together in groups near the spine, called dorsal root ganglia. If RTX were applied directly to the ganglia, the scientists knew that they could selectively delete specific neurons, such as C-fibers, that express large amounts of the VR1 protein on their surface. By doing this, they wondered whether they could also permanently turn off their chronic pain signals, which are involved in severe arthritis, peripheral neuromas, trigeminal neuralgia, and advanced cancer?
"We realized that by focusing on RTX's ability to kill cells, we could apply it therapeutically," said Dr. Laszlo Karai, an NIDCR scientist and lead author on the paper. "That might seem like a radical departure from the standard paradigm of blocking protein receptors or desensitizing them to control pain, but our laboratory data, obtained from cells in a dish, was so compelling that we thought it just might work."
As reported this month, Karai et al. performed a series of experiments in rats that showed a single injection into the trigeminal ganglion (supplies sensation to the face), or into the cerebrospinal fluid that bathes the dorsal root ganglia, (supply sensati
Contact: Bob Kuska
NIH/National Institute of Dental and Craniofacial Research