Targeted toxins may revolutionize pain therapy

Imagine being able to zap chronic pain with a single injection. That is the hope of scientists working to develop toxins that kill only certain types of neurons. A leading candidate for pain treatment is substance P-saporin, a toxin that selectively kills neurons that carry pain signals from the spinal cord to the brain.

"We have a terrible time treating patients with chronic pain--it can be nearly impossible to provide relief without side effects that sacrifice quality of life," said Dr. Ronald G. Wiley, a professor of Neurology and Pharmacology at Vanderbilt University Medical Center.

Wiley and colleagues developed substance P-saporin by linking the plant toxin saporin to substance P, a peptide that normally participates in the transmission of painful stimuli. Substance P-saporin gains entry to neurons by binding to the substance P receptors that stud the surface. Once inside, saporin halts protein production and kills the cell.

In rats, the toxin blocks the development of extreme sensitivity to pain--hyperalgesia.

"We think that hyperalgesia is the basis of our worst clinical pain problems," Wiley said.

Substance P-saporin is just the beginning. Wiley has recently developed dermorphin-saporin--a similar toxin that is directed at the mu-opiate receptor, the site of action for morphine. He will use dermorphin-saporin to study how morphine works to relieve pain. It may also offer hope to chronic pain sufferers.

"In the next few years, these tools are definitely going to extend our understanding of the neurobiology of pain," Wiley said. "In addition, they offer novel, previously never available, therapeutic potential."

Wiley and others will participate in a Society for Neuroscience symposium entitled "Exciting new advances in pain research and treatment using receptor internalization technologies" on Thursday, October 28, in Room C124. A press conference to highlight the findings will be held in room C226 on Wednesday, October 27 at 9:0

Contact: Matt Scanlan
Vanderbilt University Medical Center

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