Research directed by a scientist at Barrow Neurological Institute at St. Joseph’s Hospital and Medical Center has opened the door for the development of a new class of painkillers, called TRPV1 antagonists.

These drugs block the transient receptor potential vannilloid-1 (TRPV1) channel, which is the same receptor accountable for the feeling of hotness from hot peppers. However, clinical trials have revealed that TRPV1 antagonists cause hyperthermia– an unsafe, fever-like rise in body temperature.

Research has shown that TRPV1 can be activated by numerous stimuli, including “pepper-like” chemicals, high temperatures and protons. The same channel is to blame for pain caused by these diverse stimuli. For a number of years scientists have focused on the advance of TRPV1 antagonists, but have been stymied by the unsafe hyperthermia side effect.

The innovative project to eliminate the side effect was led by Andrej A. Romanovsky, MD, PhD, at Barrow and incorporated researchers from Amgen and Arizona State University. Their conclusions, published last month in the in the Journal of Neuroscience, show the side effect can be circumvented.

“We think we have found a recipe for making TRPV1 antagonists that do not have this fever-like side effect,” says Dr. Romanovsky. “If an antagonist does not block activation of the TRPV1channel by protons, it does not cause hyperthermia.” This study suggests that drugs that are being created should be designed not to block the proton activation of TRPV1.

Even though pain is a major clinical issue and the search for new painkillers has been carried out by pharmaceutical companies and academic scientists for numerous years, the TRPV1 channel is one of the small number of novel targets for pain identified so far. To go on with developing TRPV1 antagonists, it was important to find a way to eliminate their hyperthermic side effect. “And, this is exactly what our study did,” Dr. Romanovsky said.

Scientists believe that this new breakthrough in painkillers will be effective in treating pain related to several conditions including cancer, AIDS, migraines and diabetes.

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