The problem with opioids is that they kill pain – and people. In the past three years, more than 125,000 persons died from an opioid overdose – an average of 115 people per day – exceeding the number killed in car accidents and from gunshots during the same period.
America desperately needs safer analgesics. To create them, biochemists like myself are focusing not just on the opioids, but on opioid receptors. The opioids “dock” with these receptors in the brain and peripheral nervous system dulling pain but also causing deadly side effects.
My colleagues and I in Bryan Roth’s lab have recently solved the atomic structure of a morphine-like drug interacting with an opioid receptor, and now we are using this atomic snapshot to design new drugs that block pain but without the euphoria that leads to addiction.
What has caused the opioid epidemic?
In the U.S., more than one-third of the population experiences some form of acute or chronic pain; in older adults this number rises to 40 percent. The most common condition linked to chronic pain is chronic depression, which is a major cause of suicide.
To relieve severe pain, people go to their physician for powerful prescription painkillers, opioid drugs such as morphine, oxycodone and hydrocodone. Almost all the currently marketed opioid drugs exert their analgesic effects through a protein called the “mu opioid receptor” (MOR).
MORs are embedded in the surface membrane of brain cells, or neurons, and block pain signals when activated by a drug. However, many of the current opioids stimulate portions of the brain that lead to additional sensations of “rewarding” pleasure, or disrupt certain physiological activities. The former may lead to addiction, or the latter, death.
Which part of the brain is activated plays a vital role in controlling pain. For example, MORs are also present in the brain stem, a region that controls breathing. Activating these mu receptors, not only dulls pain but also slows breathing. Large doses stop breathing, causing death. Activating MORs in other parts of the brain, including the ventral tegmental area and the nucleus accumbens, block pain and trigger pleasure or reward, which makes them addictive. But so far there is no efficient way to turn these receptors “on” and “off” in specific areas.
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