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April 8, 2013

Pain Gene Therapy

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Researchers are developing a long-lasting way to relieve chronic pain with a single injection. As this ScienCentral video explains, the work so far has been done in rats, but researchers hope to one day offer it as an alternative when even strong drugs like morphine fail.

Interviewees: Hillary Sweet, has chronic pain;
Andreas Beutler, Mt. Sinai School of Medicine
Length: 1 min 25 sec
Produced by Sunita Reed
Edited by Sunita Reed/Chris Bergendorff
Copyright © ScienCentral, Inc.

Chronic Pain

According to the American Pain Foundation, chronic pain affects 76.2 million Americans. Hillary Sweet is one of one them. Eight years ago she had successful treatment for breast cancer. But it aggravated some minor pain she had due to bone and nerve conditions, and Sweet’s pain became so intense that even lying down on a mattress was excruciating. After trying many therapies, nurse practitioner and researcher Pat Bruckenthal finally found a combination of treatments that relieve Sweet’s pain. Sweet sees Bruckenthal at the Pain Management and Headache Treatment Center of North Shore LIJ Health Systems.

"I feel like I got my life back!" Sweet says. "I think she’s able to function and adapt to the fact that she has chronic pain very well. Not so for everybody," says Bruckenthal.

Andreas Beutler, a researcher at Mount Sinai School of Medicine who also treats cancer patients, is seeking a better way to restore what chronic pain takes away.

"Approximately 10 to 30 percent of patients with chronic pain from advanced cancer do not really get sufficient pain relief" or cannot tolerate side effects of high doses of narcotics like morphine, he says. "So they’re often in a very difficult situation of choosing to feel free of side effects or to control their pain, which is a very difficult situation for the patients and their families and for us as physicians."

When narcotics are given orally or by I-V, they flood the whole body, including the brain. This is what causes patients to sometimes become mentally clouded or suffer from hallucinations.

Seeking more effective pain treatments, Beutler turned to gene therapy. He designed a gene, called prepro-endorphin (pp EP), that tells nerve cells in the spinal cord to produce natural painkillers called beta-endorphins.

To deliver the gene, he packaged it inside a virus called sc-rAAV8 that was altered to be harmless. He tested it in rats that are sensitive to even mild pressure. To bypass the brain—and potential cognitive side effects— Beutler delivered the gene by injecting it into the fluid surrounding nerves of the spinal cord. He also tagged the gene with a protein that glows fluorescent green.

The green glow showed Beutler that the genes reached the specific nerve cells he was targeting. The rats’ nerve cells then duplicated the gene. After one month, the gene had produced enough endorphins in the nerve cells to relieve pain in the rats. The animals showed no signs of pain for three months—the length of the experiment. This figure shows nerve cells of untreated and treated rats. The glowing green in the image on the right represents the pain killing genes inside the nerve cells.

Nerve cells before and after treatment.
Pain killing genes appear green.

image: Andreas Beutler
Beutler cautions that clinical trials in people are years away, but he says his dream would be to offer a long-lasting alternative to patients who currently do not get sufficient pain relief. Beutler hopes that one day the treatment can be done by spinal tap as a bedside procedure.

In the meantime, Bruckenthal’s message to those with chronic pain is: "Don’t give up." She encourages people to go to pain specialists because they can offer a wide range of therapies including medications, physical therapy and cognitive behavioral therapies. One of the ways Sweet copes with pain is to reach out to others. She started a foundation offering free services for those affected by breast cancer, called Friends For Life.

PUBLICATION: Proceedings of the National Academy of Sciences, December 11, 2007

AUTHORS: Benjamin Storek, Matthias Reinhardt, Cheng Wang, William G. M. Janssen, Nina M. Harder, Michaela S. Banck, John H. Morrison, and Andreas S. Beutler

RESEARCH FUNDED BY: Neurological Disorders and Stroke, American Society of Clinical Oncology, G&P Foundation and T. J. Martell Foundation

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