Pest control research leads to pain control discovery

August 28, 2006

A newly discovered enzyme inhibitor, identified by researchers originally looking for biological pest controls, may lead to pain relief for sufferers of arthritis and other inflammatory diseases, say researchers at the University of California, Davis. The finding, hailed by a noted inflammatory disease expert "as the most important discovery in inflammation in more than a decade," may also reduce side effects associated with the painkiller, Vioxx.

Lead author Kara Schmelzer, a post-doctoral researcher in principal investigator Bruce Hammock's lab, tested the novel compounds on rodents and found them to be as potent at a low-dose as Vioxx and Celebrex, but without the changes in blood chemistry linked to heart attacks. Vioxx and Celebrex belong to a class of drugs known as Cox-2 inhibitors. The enzyme targeted by the newly discovered inhibitors is also found in humans. (Enzymes are proteins that speed up chemical reactions.)

"The reason this is so exciting is that this is a novel way to reduce inflammation, with a combination therapy," Schmelzer said. "We're going after a new enzyme target, not going after the Cox-2 inhibitors."

Their research is reported in a paper entitled "Enhancement of Antinociception by Coadministration of Nonsteroidal Anti-Inflammatory Drugs and Soluble Epoxide Hydrolase Inhibitors," published in the current edition of Proceedings of the National Academy of Sciences.

"Our laboratory was initially interested in regulating the development of insect larvae," said Hammock, a distinguished professor of entomology and member of the National Academy of Sciences. The discovery switched the focus of the research from "pest control to pain control."

M. Eric Gershwin, chief of the Division of Rheumatology, Allergy and Clinical Immunology at the UC Davis School of Medicine and a distinguished professor of medicine, called the discovery "the most important discovery in inflammation in more than a decade." Gershwin, who was not affiliated with this study, is noted for his research on rheumatoid arthritis and other inflammatory diseases. His lab investigates the mechanisms leading to immunological alterations and autoimmunity.

As of 2004, physicians prescribed anti-inflammatory medication for more than 73 million patients. But many of the people suffer from pharmacological properties or side effects of the medications. Merck, the pharmaceutical company that manufactured and marketed Vioxx, a Cox-2 selective nonsteroidal anti-inflammatory drug (NSAID), voluntarily pulled the pain killer from the market in September 2004 due to safety concerns. A 12-month study, published in 2000, showed a four-fold increased risk of heart attacks. Merck hopes to replace it with another medication, Acoxia.

However, the class of drugs benefits millions of sufferers from inflammation and pain, Hammock said. The UC Davis study may mean a solution to the dilemma of whether to use the drugs.

"Combination therapies have long been used to treat inflammation while reducing side effects," Schmelzer wrote. She said the present study was designed to evaluate the therapeutic potential of combination treatment with NSAIDs and enzyme inhibitors (a previously undescribed soluble epoxide hydrolase inhibitor or sEHIs) in lipopolysaccharide (LPS)-challenged mice.

"We used LPS as an inflammatory agent, which is a component of some bacterial cell walls," said, co-author Steven Jinks. His laboratory examined the effects of these compounds in rodent inflammatory pain ehavior models. "Inflammatory mediators sensitize pain receptors and cause the animal to withdraw more quickly from a noxious stimulus, an indication of 'hyperalgesia' or heightened response to a painful stimulus. The sEH inhibitors reverse hyperalgesia and bring their withdrawal reaction back into the normal range.

Hammock said "these sEHIs are of similar or greater potency in reducing inflammation in rodents to Vioxx, but also when combined with Vioxx can dramatically reduce the concentrations of the Cox 2 inhibitor needed," Hammock said.

"The combination of Vioxx with the new sEHIs shifts blood chemistry toward the normal condition which may reduce the tendency toward blood clots," said UC Davis scientist Bora Inceoglu, a post-doctoral researcher and member of the research team.
-end-
The paper will be online at http://www.pnas.org/.

Schmelzer, Inceoglu and Hammock teamed with: In-Hae Kim, post-doctoral researcher in Hammock's lab; Steven Jinks, assistant adjunct professor, Department of Anesthesiology and Pain Medicine, UC Davis School of Medicine; Jason Eiserich, associate professor, Division of Nephrology, Department of Internal Medicine, UC Davis School of Medicine; and Lukas Kubala, former UC Davis post-doctoral researcher in Eiserich's lab.

Four UC Davis departments collaborated on the project: entomology, internal medicine, anesthesiology and pain medicine, and physiology and membrane biology, along with the UC Davis Cancer Research Center.

The work drew grant support from the National Institute of Environmental Health Sciences, Superfund Basic Research Program, and the Center for Children's Environmental Health and Disease Prevention, as well as a research award from the UC Davis Health Systems to Eiserich; a Paul F. Gulyassy Endowed Professorship to Eiserich and a UC Davis Department of Anesthesiology and Pain Medicine award to Jinks.

University of California - Davis

Related Inflammation Articles from Brightsurf:

3D printed stents that treat inflammation
POSTECH Professor Dong-Woo Cho's research team develops bioink-loaded esophageal stents for treating radiation esophagitis.

New cause of inflammation in people with HIV identified
A new study led by researchers at Boston Medical Center examined what factors could be contributing to this inflammation, and they identified the inability to control HIV RNA production from existing HIV DNA as a potential key driver of inflammation.

Maltreatment tied to higher inflammation in girls
New research by a University of Georgia scientist reveals that girls who are maltreated show higher levels of inflammation at an early age than boys who are maltreated or children who have not experienced abuse.

A protein that controls inflammation
A study by the research team of Prof. Geert van Loo (VIB-UGent Center for Inflammation Research) has unraveled a critical molecular mechanism behind autoimmune and inflammatory diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis.

Inflammation in the brain linked to several forms of dementia
Inflammation in the brain may be more widely implicated in dementias than was previously thought, suggests new research from the University of Cambridge.

Social isolation could cause physical inflammation
Social isolation could be associated with increased inflammation in the body new research from the University of Surrey and Brunel University London has found.

Hydrogels control inflammation to help healing
Researchers test a sampling of synthetic, biocompatible hydrogels to see how tuning them influences the body's inflammatory response.

Why beta-blockers cause skin inflammation
Beta-blockers are often used to treat high blood pressure and other cardiovascular diseases.

The 'inflammation' of opioid use
New research correlates inflammation in the brain and gut to negative emotional state during opioid withdrawal.

Using a common anticonvulsant to counteract inflammation
The interaction between a chromosomal protein called HMGB1 and a cellular receptor called RAGE is known to trigger inflammation.

Read More: Inflammation News and Inflammation Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.