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January 12, 2018
Digest
Chemical from Cactus-Like Plant Shows Promise Controlling Surgical Pain, Study Shows

A promising approach to post-operative incision-site pain control uses a naturally occurring plant molecule called resiniferatoxin (RTX). RTX is found in Euphorbia resinifera, a cactus-like plant native to Morocco that is 500 times more potent than the chemical that produces heat in hot peppers and may help limit the use of opioid medication while in the hospital and during home recovery.

A chemical in Euphorbia resinifera, a cactus-like plant pictured above, shows promise for pain relief.
A chemical in Euphorbia resinifera, a cactus-like plant pictured above, shows promise for pain relief.

IMAGE: BS THURNER HOF/WIKIMEDIA COMMONS

In a paper published online in Anesthesiology, researchers found that RTX could be used to block post-operative incisional pain in an animal model.

Many medical providers turn to opioids, such as morphine or fentanyl, for moderate to severe post-operative pain relief, but these often come with side effects that can interfere with recovery, including respiratory depression, inhibition of gut motility and constipation, nausea and vomiting.

Prolonged use of opioids can produce tolerance and introduces the risk of misuse. RTX is not an opioid and does not act in the brain but rather on the nerve endings in the skin. Scientists found that it can be used to block pain from the surgical incision selectively for approximately 10 days.

In the study, researchers pre-treated the skin incision site with RTX to render the nerve endings in the skin and subcutaneous tissue along the incision path selectively insensitive to pain. Unlike local anesthetics, which block all nerve activity including motor axons, RTX allows many sensations, like touch and vibration, as well as muscle function, to be preserved. Long after the surgery, and towards the end of healing of an incision wound, the nerve endings eventually grow back. Thus, pain from the skin incision is reduced during the recovery period.

Study Uncovers Clues About Why Common Cancer Drug Causes Hearing Loss

Scientists have found a new way to explain the hearing loss caused by cisplatin, a powerful drug used to treat many forms of cancer. Using a highly sensitive technique to measure and map cisplatin in mouse and human inner ear tissues, researchers found that forms of cisplatin build up in the inner ear. They also found a region in the inner ear that could be targeted for efforts to prevent hearing loss from cisplatin. The study is published in Nature Communications and was supported by NIDCD.

Cisplatin and similar platinum-based drugs are prescribed for an estimated 10 to 20 percent of all cancer patients. NCI supported research that led to the 1965 discovery of cisplatin and continued development leading to its success as an essential weapon in the battle against cancer. The drugs cause permanent hearing loss in 40 to 80 percent of adult patients and at least half of children who receive the drug.

The new findings help explain why cisplatin is so toxic to the inner ear and why hearing loss gets worse after each treatment, can occur long after treatment and is more severe in children than adults.

“Hearing loss can have a major impact on a person’s life,” said NIDCD director Dr. James F. Battey Jr. “Many adults with hearing loss struggle with social isolation and depression, among other conditions. Children who lose their hearing often have problems with social development and keeping up at school. Helping to preserve hearing in cancer patients who benefit from these drugs would be a major contribution to the quality of their lives.”

Dr. Lisa L. Cunningham of NIDCD led the research team, which included scientists from NIMHD and NCATS.

In most areas of the body, cisplatin is eliminated within days or weeks after treatment, but in the inner ear, the drug remains much longer. Previous research focused on why the inner ear is more sensitive than other parts of the body to cisplatin-induced damage. The NIH team pursued a new angle on the problem: What if the inner ear is not able to get rid of cisplatin and cells in the inner ear important for hearing die because they are exposed to the drug for a long time?

The team developed a mouse model that represents cisplatin-induced hearing loss seen in human patients. By looking at inner ear tissue of mice after the first, second and third cisplatin treatment, researchers saw that cisplatin remained in the mouse inner ear much longer than in most other body tissues and that it builds up with each successive treatment. They also studied inner ear tissue donated by deceased adult patients who had been treated with cisplatin and observed that cisplatin is retained in the inner ear many months or years after treatment.

Defending Against Environmental Stressors May Shorten Lifespan

A shorter life may be the price an organism pays for coping with the natural assaults of daily living, according to researchers at NIH and colleagues in Japan. The scientists used fruit flies to examine the relationship between lifespan and signaling proteins that defend the body against environmental stressors, such as bacterial infections and cold temperatures.

Scientists used fruit flies to examine the relationship between lifespan and signaling proteins that defend the body against environmental stressors, such as bacterial infections and cold temperatures.
Scientists used fruit flies to examine the relationship between lifespan and signaling proteins that defend the body against environmental stressors, such as bacterial infections and cold temperatures.

IMAGE: USDA

Since flies and mammals share some of the same molecular pathways, the work may demonstrate how the environment affects longevity in humans.

Appearing in the Proceedings of the National Academy of Sciences, the research identified Methuselah-like receptor-10 (Mthl10), a protein that moderates how flies respond to inflammation. The finding provides evidence for one theory of aging, which suggests longevity depends on a delicate balance between proinflammatory proteins, thought to promote aging, and anti-inflammatory proteins, believed to prolong life. These inflammatory factors are influenced by what an organism experiences in its everyday environment.

Corresponding author Dr. Stephen Shears of NIEHS explained that Mthl10 appears on the surface of insect cells and acts as the binding partner to a signaling molecule known as growth-blocking peptide (GBP).

Once Mthl10 and GBP connect, they initiate the production of proinflammatory proteins, which, in turn, shortens the fly’s life. However, removing the Mthl10 gene makes the flies unable to produce Mthl10 protein and prevents the binding of GBP to cells. As a result, the flies experienced low levels of inflammation and longer lifespans.

“Fruit flies without Mthl10 live up to 25 percent longer,” Shears said. “But, they exhibit higher death rates when exposed to environmental stressors.”

Shears said the research reveals that the ability of a young organism to defend against repeated environmental stress may be an empty victory, because the animal may not live as long. He believes the research may contribute to the discovery of drugs that target excess inflammation induced by signaling proteins in humans, extending life.

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