Gene Therapy Can Control Pain

Embargoed until March 15 at 5 p.m. EST

UIC RESEARCHER REPORTS GENE THERAPY CAN CONTROL PAIN Collaborative study at three universities is first of its kind

A University of Illinois at Chicago researcher and colleagues at the University of South Carolina and the University of Pittsburgh report in the March 16 issue of Proceedings of the National Academy of Sciences that gene therapy is effective in controlling pain in animals.

The research focused on mice exhibiting pain-associated behaviors. The animals were treated with a herpes virus containing the gene that triggers production of the pain-blocking protein preproenkephalin.

"Our results show that the treatment model appears to act 'on demand,'" said David Yeomans, professor of anatomy and cell biology and anesthesiology at UIC. "That is, while the virus doesn't affect pain thresholds, it does block ongoing or strong pain, and the hypersensitivity that comes with this kind of pain."

Yeomans designed and performed the experiments that demonstrated the pain-blocking protein was in fact being produced and the behavioral experiments that demonstrated the pain-relieving effect of the virus.

The research team expects that, within several years, gene therapy could be used broadly to treat debilitating pain associated with cancer, arthritis, angina and peripheral neuropathies.

Currently, these problems are often treated with narcotic-based medications given systemically, which can cause generalized side effects such as mental confusion and lethargy. Moreover, they are potentially addictive and in some cases ineffective for complete relief of pain.

Specifically, Yeomans and the other researchers found that the gene successfully entered and worked within both of the major types of pain-sensing neurons. One transmits information felt as slow burning pain and other is involved in sharp pain felt by humans. This observation is particularly encouraging for future clinical applications, because these neurons are thought to be primary transmitters of chronic pain.

"This treatment could offer strong, localized and long-lasting relief for pain that is otherwise difficult to treat," said Yeomans. "You have to keep administering and increasing the dosage of narcotic-based medications given systemically. This gene therapy approach could dramatically change the way chronic-debilitating pain is treated."

Joseph Glorioso, professor and chairman of the department of molecular genetics and biochemistry at the University of Pittsburgh, who took part in the study, added, "Our engineered herpes virus used for this research is exceptionally well-suited to deliver genes for pain relief."

Experiment Details: In their experiments using a gene for preproenkephalin, the investigators showed that once inside the body, this substance is enzymatically processed into opiate-like peptides known as enkephalins. The researchers placed the gene inside a herpes virus capable of establishing latency in the nervous system, a state where the viral genes are inactive while the enkephalin gene remains active. The researchers transferred the gene-containing virus to the paws of mice, where it naturally infected sensory neurons including those that respond to noxious stimuli such as heat. In the experiments, the gene-containing virus continued to produce the pain-blocking protein up to seven weeks after it was introduced into the animals.

"These results are quite exciting, because we don't interfere with an animal's ability to detect noxious stimuli and withdraw its paw from danger," said Steven Wilson, professor of pharmacology and physiology at the University of South Carolina and a collaborator on this project. "Only when sensitivities to noxious stimuli are enhanced, a phenomenon that may be important in chronic pain states, does the gene therapy act, with the result that gene-treated animals respond more slowly to this hyper-stimulation than do untreated ones," he added.

-UIC-