Approaching Painkillers Differently

Opioid addiction may become a thing of the past if painkillers no longer trigger a reward

(RxWiki News) What if painkillers killed pain without getting people high? People without pain would feel nothing and people with pain would feel pain-free and clearheaded.

A recent pre-clinical trial tested the drug (+)-naloxone on opioid addicted rats. (+)-naloxone binds to immune receptors, rather than opioid receptors, bypassing the reward response.

"Talk to your doctor if you are addicted to opioids."

Mark Hutchinson, PhD, research fellow in physiology at the School of Medical Sciences at The University of Adelaide in Australia, and Linda Watkins, PhD, professor of neuroscience at the University of Colorado at Boulder, led a study into blocking heroin and morphine absorption in the brain.

This pre-clinical trial tested the drug (+)-naloxone on rats given open access to opioids.

In their approach to the global health issue of opioid addiction, scientists thought outside the box and approached things from a different angle.

They engaged the immune response as well, rather than opioid receptors in the brain alone.

Up until now, approached to developing prescriptions to help with opioid addiction have focused on blocking opioid receptors and disrupting the rewards response of feeling high.

But, the immune system is also involved with addiction, specifically, the Toll-like receptor 4 (TLR4).

Dr. Hutchinson said, “Our studies have shown conclusively that we can block addiction via the immune system of the brain, without targeting the brain’s wiring.”

“Both the central nervous system and the immune system play important roles in creating addiction, but our studies have shown we only need to clock the immune response in the brain to prevent cravings for opioid drugs.”

“Opioid drugs such as morphine and heroin bind to TLR4 in a similar way to the normal immune response to bacteria. The problem is that TLR4 then acts as an amplifier for addiction.”

“The drug (+)-naloxone automatically shuts down the addiction. It shuts down the need to take opioids, it cuts out behaviors associated with addiction, and the neurochemistry in the brain changes—dopamine, which is the chemical important for providing that sense of ‘reward’ from the drug, is no longer produced.”

Authors call it the role of (+)-naloxone a, “central proinflammatory immune signaling in drug reward.”

These new findings have implications for helping heroin and morphine addicts, as well as preventing people who need painkillers from becoming addicts.

Dr. Watkins said, “This work fundamentally changes what we understand about opioids, reward and addiction. We’ve suspected for some years that TLR4 may be the key to blocking opioid addiction, but now we have proof.”

Dr. Watkins added that if they can formulate (+)-naloxone with morphine to successfully manage pain without addiction potential, it would be a major advance in patient care.

This study was published in August in The Journal of Neuroscience. Funding was provided by the National Institute on Drug Abuse in the U.S. and the Australian Research Council, no conflicts of interest were reported.

Review Date: 
August 17, 2012