Non-Addictive Painkillers
> 11/26/2007 1:24:52 PM

The development of powerful pharmaceutical painkillers has been both a blessing and a curse. Synthetic opioids can very effectively relieve unbearable pain but carry the considerable risk of creating an addiction every bit as severe as that experienced by hard drug users. It seemed that we would have to accept the double edged nature of these wonder drugs. But in August, researchers at the Washington University School of Medicine found evidence that the two effects could, in theory, be separated. They discovered that morphine-exposed mice who had been engineered to lack the pleasure-reward neurotransmitter serotonin suffered symptoms of opioid withdrawal and addiction even though they were unable to experience the pain-killing benefits of these medications, demonstrating that intoxicating and pain-killing properties of the given substances work through different mechanisms. We covered this revelation with excitement but kept our optimism in check because no practical drug had yet been created.

Driven by the theoretical possibility of developing a non-addictive painkiller, researchers at the University of Adelaide began the search for such a drug in earnest. The first breakthrough came when they looked closely at laboratory animals and noticed that opioids activate two distinct types of cells: nerve cells, or neurons, and the immune cells in the brain called glial cells. Glial cells actually heighten pain, and when activated they facilitate cravings and addiction. Researchers developed a drug called AV411 to block the stimulation of glial cells while allowing opioids to affect neurons.

Rats given AV411 and morphine showed better tolerance for pain than rats dosed only with morphine. This finding alone would make the development of AV411 a big step towards relieving the suffering experienced by major surgery patients or victims of chronic pain. What made it a massive breakthrough was the fact that mice given AV411 showed no signs of craving morphine. Normally, when mice learn that one corner of their cage is the only place where an opioid is administered, they return there again and again (if they ever leave). However, mice given AV411 wandered blithely around their cages, indifferent to the prospect of getting more morphine.

A non-addictive painkiller will allow doctors to treat pain adequately without worrying that they are hooking their patients or feeding the deceptive pleas of an addict. With prescription pain-killers rivaling traditional narcotics in addiction numbers, AV411 has the potential to save many lives in addition to alleviating much suffering. Even if this specific drug does not work in humans, it is now clear that non-addictive painkillers are possible and it should only be a matter of time before a viable one is discovered.

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