Researchers Develop Two New Classes of Analgesics

Scientists at the University of Texas Health Science Center at San Antonio developed a new class of non-addictive painkillers based on the discovery of a new family of fatty acids.

Scientists at the University of Texas Health Science Center at San Antonio developed a new class of non-addictive painkillers based on the discovery of a new family of fatty acids.

The team, led by senior investigator Kenneth Hargreaves, DDS, PhD, found that these fatty acids, which are produced within the body, play an important role in the biology of pain.

The experiments focused on blocking a capsaicin-like substance that is generated at the site of pain.

°

transient potential vanilloid 1 (TRPV1) receptor, which is activated during painful activity or heat, had been knocked out. The researchers found that neurons from the wild type mice were sensitive to capsaicin, while the neurons with the deleted TRPV1 receptor were not affected.

The researchers heated flaps of skin from laboratory mice to temperatures greater than 43 Celsius, the point at which the human body normally begins to feel pain and discomfort. The heated flaps of skin were then applied to sensory neurons that were cultured from two sets of laboratory mice. In on set of mice, the

“We found that in the skin flaps heated at greater than 43 degrees Celsius, the cells’ pain neurons showed tremendous activity in the wild type, but not in neurons from mice that lacked TRPV1,” Hargreaves said, indicating “that this novel phenomenon was taking place because the cells, in response to the heat, began to create their own natural endogenous capsaicins, which they later identified as a series of compounds or fatty acids called oxidized linoleic acid metabolites (OLAMs).”

The research led to the development of two new classes of analgesics that either block the synthesis of OLAMs or antibodies that inactivate them, drugs that could eventually be administered in several forms.

“This is a major breakthrough in understanding the mechanisms of pain and how to more effectively treat it,” Hargreaves said. “These data demonstrate, for the first time, that OLAMs constitute a new family of naturally occurring capsaicin-like agents, and may explain the role of these substances in many pain conditions. This hypothesis suggests that agents blocking either the production or action of these substances could lead to new therapies and pharmacological interventions for various inflammatory diseases and pain disorders such as arthritis, fibromyalgia and others, including pain associated with cancer.”

Journal of Clinical Investigation

.

Results of the study were also published in the