New Discovery May Revolutionize Chronic Pain Treatment

Researchers at the University of California made a discovery that may revolutionize how chronic pain is controlled: a “cross-talk” between two major biological pathways in the body.

The study, which is published in the Proceedings of the National Academy of Sciences, revealed that “analgesia mediated by inhibitors of the enzyme, soluble epoxies hydrolase (sEH), is dependent on a pain-mediating second messenger known as cyclic adenosinemonophosphate or cAMP,” said web-article from Physorg.

“The interaction of many complex biological pathways is essential for the development of persistent pain, whether inflammatory or neuropathic,” said Bora Inceoglou, lead researcher and researcher of the Bruce Hammock lab in the UC Davis Department of Entomology.

The intention of the research the scientists were conducting was not related to this finding, but it was a happy discovery. “To our surprise, we found that cAMP interacts with natural EFAs [epoxy-fatty acids] and regulates the analgesic or pain activity of sEH inhibitors,” Inceoglu said.

The research confirmed earlier studies done at UC Davis which showed the stabilization of natural EFAs through inhibition of sEH reduces pain; this "permits normal pain responses that serve to protect us from tissue damage to remain intact, while alleviating debilitating pain,” said co-author and pain neurobiologist Steven Jinks, associate professor of anesthesiology and pain medicine, UC Davis School of Medicine.

Hammock, senior author of the paper and a distinguished professor of entomology who holds a joint appointment with the UC Davis Cancer Research Center, explained the discovery process.

The research involved “an old class of drugs known as phosphodiesterase inhibitors that likely exert part of their action by increasing the levels of natural compounds in the body called EETs [epoxyeicosatrienoic acids].” Previous research at the lab reported that a new class of experimental drugs called soluble epoxide hydrolase inhibitors (sEHIs) stabilize and also increase EETs.

“A practical application of this work demonstrated by Bora Inceoglu is that the combination of this old and new class of drugs are highly effective in controlling pain,” said Hammock. “Of course, the basic aspects of the work include new insights in how EETs, cyclic nucleotides and the enzymes that degrade them interact to regulate a variety of biological functions.”

According to the American Pain Society, it is estimated that 9 percent, or 30 million, adults in America suffer from some level of chronic pain unrelated to the chronic pain of cancer.

While pain killing medications target the pain of a patient, they may not always be effective enough to reduce the pain to a tolerable level; side effects are also always a downside. “Pain is a major health concern and painkiller medications or analgesics do different things,” Inceoglu said.

Karen Wagner, a graduate student research of the Hammock lab team, said that an “advantage of inhibition of sEH is that it does not impair motor skills in several tests, unlike other analgesics.”

Hammock reported feeling excited at the potential this discovery has. “We all have both suffered pain and have friends with unrelenting chronic pain problems,” he said. “The possibility of combining members of an old class of drugs with our new sEHI and actually providing relief for pain is very exciting.”