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Of Mice Not Men: Chemical from cactuslike plant kills pain in rats

This is a recurring column on early stage research in animals or other laboratory models that has not entered the clinic yet but could have implications for future research and development of human medicines.

Molecule from Moroccan cactuslike plant shows promise in post-operative pain control

A molecule derived from a cactuslike plant native to Morocco has been successfully used to block incision-site pain in rats after an operation.

The molecule is called resiniferatoxin, or RTX, and is 500 times more potent than the chemical that produces heat in hot peppers. It may ultimately help to curb the use of opioids while in the hospital and during recovery from an operation, according to researchers at the U.S. National Institutes of Health Clinical Center.

RTX is not an opioid and does not act in the brain but on nerve endings in the skin. Researchers found that it could be used to selectively relieve the pain from an incision following surgery for approximately 10 days afterward in animal models. Scientists pretreated the site by injecting RTX under the skin where the incision was to occur to make the nerve endings in the skin and the subcutaneous tissue along the incision path insensitive to pain.

"This is actually an extremely simple concept to get across," Michael Iadarola, who led the research at the NIH Clinical Center, told S&P Global Market Intelligence in an interview.

SNL Image

A cactuslike plant native to Morocco produces a chemical that has been shown to block pain, U.S. researchers reported.

Source: Associated Press

RTX allows many sensations such as touch, vibration and muscle function to be preserved — unlike local anesthetics, which block all nerve activity. "We didn't exactly discover this compound, but we discovered how to use it," Iadarola said. "Basically we block all of the post-operative pain at the site of the skin, and somewhat deeper, and by the time the pain fibers come back, the wound is healed."

Opioids such as morphine and fentanyl, often used for post-operative pain, come with side effects that can include nausea and vomiting, constipation and the risk of misuse. The U.S. opioid epidemic is getting worse, and effective, less-addictive alternatives to those drugs are in demand.

Iadarola said he has researched the compound for use in humans as an eye drop for pain such as a corneal abrasion, in severe pain associated with advanced cancer and in animals with osteoarthritis, among other uses.

He has just submitted a paper about an osteoarthritis study he conducted with dogs, in which RTX was administered into a canine knee or elbow joint. A very long duration was observed, with pain suppression of a median of five months and the longest effect up to 18 months.

"I've undertaken this study with everything," said Iadarola. "Name a pain problem that I haven't done!"

Experimental contraceptive for men blocks sperm in monkeys

Researchers have developed a compound that temporarily interferes with sperm mobility in monkeys, raising the potential that a reversible male contraceptive might be developed, offering an alternative to condoms or vasectomy.

Michael O'Rand led a team of scientists at the University of North Carolina at Chapel Hill along with local company Eppin Pharma Inc., focusing on the sperm surface protein EPPIN after finding that compounds that bind to it interfere with sperm mobility.

The researchers created a compound called EP055 and found that within 30 hours of injecting it into four rhesus macaque monkeys, sperm mobility had dropped below 32%, a level considered too low to penetrate the tough outer layer of an egg to fertilize it. After a higher dose was administered, within six to eight hours the sperm's ability to mobilize had dropped to about 20%.

Investigators have been trying to develop another contraceptive option for men by either turning off sperm production or limiting its mobility by impairing its ability to swim toward the egg. These results, published in the medical journal PLOS ONE on April 19, demonstrated that sperm mobility levels remained low in three of the four monkeys for at least 78 hours after the infusions and had recovered fully 18 days later. No side effects were detected in the monkeys.

"Simply put, the compound turns off the sperm's ability to swim, significantly limiting fertilization capabilities," O'Rand said. "This makes EP055 an ideal candidate for nonhormonal male contraception."

The researchers have begun to formulate a pill version of the compound to carry out further tests in lab animals.