Fighting pain fivefold better?

COLUMBIA, Mo.—Medications have long been used to treat pain caused by injury or chronic conditions. Unfortunately, most are short-term fixes or cause side effects that limit their use. Researchers at the University of Missouri (MU), however, have discovered a new compound that seems to offer longer-lasting painkilling effects and shows promise as an alternative to current anesthetics.

“Because of its versatility and effectiveness at quickly numbing pain in targeted areas, lidocaine has been the gold standard in local anesthetics for more than 50 years,” according to Dr. George Kracke, associate professor of anesthesiology and perioperative medicine at the MU School of Medicine and lead author of the study. “While lidocaine is effective as a short-term painkiller, its effects wear off quickly. We developed a new compound that can quickly provide longer-lasting relief. This type of painkiller could be beneficial in treating sports injuries or in joint replacement procedures.”

“The goal of any local anesthetic is to block sensory nerves to reduce the level of pain sensation,” notes Kracke, “but at the same time not affect motor function in the injured limb in a sports injury or postoperative recovery after joint replacement surgery. Further testing of our compounds will be needed to see to what extent they are able to block sensory nerves in preference to motor nerves. If they are able to do this better than currently used local anesthetics, this would be a significant advance in pain medicine.”

Painkillers work by interfering with the nervous system’s transmission of nerve signals that the body perceives as pain. Lidocaine is used as an injectable pain reliever in minor surgical or dental procedures, or as a topical ointment or spray to relieve itching, burning and pain from shingles, sunburns, jellyfish stings and insect bites. The new compound developed at MU, boronicaine, could potentially serve many of those same functions as an injectable or topical painkiller. National Academy of Sciences member Dr. M. Frederick Hawthorne, director of MU’s International Institute of Nano and Molecular Medicine and a pioneer in the field of boron chemistry, synthesized boronicaine as a derivative of lidocaine. By changing aspects of the chemical structure of lidocaine, the researchers found that the new compound provided pain relief that lasted five times longer than lidocaine. In preclinical studies, boronicaine provided about 25 minutes of relief, compared to about five minutes of pain relief with lidocaine.

“Although some conditions may warrant the use of a short-lasting painkiller, in many cases a longer-lasting anesthetic is a better option,” Kracke said. “Having a longer-lasting anesthetic reduces the dosage or number of doses needed, limiting the potential for adverse side effects.”

While other types of painkillers can provide longer pain relief than lidocaine, they can cause heart toxicity, gastrointestinal issues and other side effects. Preliminary findings show no toxicity in single-dose studies of boronicaine, though more studies are needed.

“Boronicaine could have distinct advantages over existing painkilling medications,” said Hawthorne, who also serves as the Curators’ Distinguished Professor of Chemistry and Radiology at MU. “We’re conducting more research into the side effects of the compound, but in time it could very well become a useful material to use as an anesthetic.”

Specificity is important in local anesthetic action, Kracke notes. “Local anesthetics target voltage-gated sodium channels, some of which are specific to particular organs such as the heart, skeletal muscle or central nervous system. Our next step will be to test our new painkiller on an array of cloned sodium channels derived from various tissues and compare them to lidocaine, a widely used local anesthetic. Some local anesthetics such as bupivacaine have adverse effects on cardiac function, and this property can compromise its use as an analgesic. In addition, we will do further testing on other cardiac ion channels in order to learn about their possible effects on the heart.”

The study, “Carborane-derived Local Anesthetics Show Isomer-dependent Analgesia,” was presented on March 29 at the Experimental Biology 2015 conference in Boston, and the research was recently published in the medicinal chemistry journal ChemMedChem. The research is funded by the University of Missouri System Intellectual Property Fast Track Funding Program, the MU International Institute of Nano and Molecular Medicine and the MU Department of Anesthesiology and Perioperative Medicine.