The Promise of New Painkillers

For thousands of years, humans have used the extracts of the poppy plant for pain relief. In the last 200 years, opium and the more refined morphine and its derivatives have been the go-to medicine for pain relief, particularly after surgery. But the side effects are horrendous. While nothing better for pain relief has been found, scientists are working on opioids to separate the painkilling effects from the other effects.

Traditional opioids—including morphine, the potent synthetic fentanyl and the Vicodin you get from your dentist—all work by binding to opioid receptors in the nervous system. These receptors come in three flavors: mu, delta and kappa. It’s at the mu-opioid receptor that opioids work their magic, activating a cascade of cellular signaling that triggers their pain-relieving effects. In the language of neuroscience, opioids are mu-receptor “agonists,” as opposed to “antagonists,” which are compounds that bind to a receptor and block it, preventing cellular signaling. When an opioid binds with the mu-opioid receptor, it ultimately turns down the volume on the nerves communicating pain. This, of course, is the desired effect.
Unfortunately, that’s not all it does. Opioids also release the neurotransmitter dopamine, which causes euphoria and can lead to addiction. These compounds also inhibit nerve cells from firing more generally, including in parts of the brain that regulate breathing—which can be dangerous. Take too much of an opioid and you stop breathing and die; that’s what it is to overdose. The CDC estimates that 91 Americans die every day from an opioid overdose. The side effects go on, from constipation to nausea to the rapid development of tolerance so that ever higher doses are needed for the same effect.

But what if we could refine opium to only effect the mu receptors and not the others? That would kill pain without the high? Or that wouldn't inhibit respiration? Several new formulations are in the works, including Oliceridine, which works even faster than morphine and is now in Phase III clinical trials. Read about the research into a better painkiller at Smithsonian.