Saturday, August 20, 2016

Once people realized that opioid drugs could cause addiction and deadly overdoses, they tried to use newer forms of opioids to treat the addiction to its parent. Morphine, about 10 times the strength of opium, was used to curb opium cravings in the early 19th century. Codeine, too, was touted as a nonaddictive drug for pain relief, as was heroin.

Those attempts were doomed to failure because all opioid drugs interact with the brain in the same way. They dock to a specific neural receptor, the mu-opioid receptor, which controls the effects of pleasure, pain relief and need.

Now scientists are trying to create opioid painkillers that give relief from pain without triggering the euphoria, dependence and life-threatening respiratory suppression that causes deadly overdoses.

That wasn't thought possible until 2000, when a scientist named Laura Bohn found out something about a protein called beta-arrestin, which sticks to the opioid receptor when something like morphine activates it. When she gave morphine to mice that couldn't make beta-arrestin, they were still numb to pain, but a lot of the negative side effects of the drug were missing. They didn't build tolerance to the drug. At certain dosages, they had less withdrawal. Their breathing was more regular, and they weren't as constipated as normal mice on morphine.

Before that experiment, scientists thought the mu-opioid receptor was a simple switch that flicked all the effects of opioids on or off together. Now it seems they could be untied. "The hope is you'd have another molecule that looks like morphine and binds to the same receptor, but the way it turns the receptor on is slightly different," says Dr. Aashish Manglik, a researcher at Stanford University School of Medicine who studies opioid receptors.

After Bohn's discovery, a number of people, including a team that includes Manglik, started looking for a drug that could connect to the mu-opioid receptor in a way that avoids the negative effects of beta-arrestin.

To do that, they mapped the receptor's structure in a computer program and started looking for chemicals that would stick to it. "We tried to look for molecules that would still bind to this 3-D structure, but are as far away from morphine and codeine as possible," Manglik says.

The team ran 3 million possibilities through the computer and picked the 23 best candidates to test in a lab. One chemical, PZM21, seems to do what they hoped: Turn the opioid receptor on without using much beta-arrestin. They report their findings in Nature on Wednesday.

Within minutes of our first meeting, and more or less in response to my saying good morning, Justin Schmidt began lamenting our culture's lack of insect-based rites of passage. He told me about the Sateré-Mawé people in northwestern Brazil, who hold a ceremony in which young men slip their hands into large mitts filled with bullet ants, whose stings are so agonizing they can cause temporary paralysis; when initiates pass the test, they're one step closer to becoming full members of society.

Schmidt believes we could learn something from this. By trade, he is an entomologist, an expert on the Hymenoptera order — wasps, bees and ants — but his interest in this insect ritual was not merely academic. He has two teenage boys, and, on this particular morning at least, I found him wondering whether they might benefit from a pain ritual to help introduce them to adulthood.

"I mean, it wouldn't kill them," Schmidt said. "And I think that may be the key to the whole thing: It can't kill you and yet something very real is happening."

It was a bit before 7:30 on a windy weekday morning in Tucson, and Schmidt had just dropped off his 14-year-old at school. At 69, Schmidt has a head of red hair that stubbornly refuses to go gray and a boyish face that glints of mischief. We were driving in his 1999 Toyota Corolla down a road that may have been a desert highway or a city thoroughfare: My East Coast eyes couldn't tell the difference. We pulled up to a traffic light, next to a giant saguaro cactus whose short, upturned arm gave it the look of a crossing guard gesturing us to stop.

Schmidt's new book, "The Sting of the Wild: The Story of the Man Who Got Stung for Science," weaves his theories about stinging insects through a narrative of his personal experiences digging in the dirt. For many readers, the highlight of the book will be the appendix, his celebrated Pain Scale for Stinging Insects, which rates the pain level of dozens of insect stings, an index he created mostly by firsthand experience, either by suffering stings incidentally during field research or, in some cases, by inducing them.

Because stings of the same magnitude don't necessarily feel the same, Schmidt has written haiku-like descriptions for each of the 83 sting entries:

Tuesday, August 09, 2016

Roslyn Lewis was at work at a dollar store here in Tuscaloosa, pushing a heavy cart of dog food, when something popped in her back: an explosion of pain. At the emergency room the next day, doctors gave her Motrin and sent her home.

Her employer paid for a nerve block that helped temporarily, numbing her lower back, but she could not afford more injections or physical therapy. A decade later, the pain radiates to her right knee and remains largely unaddressed, so deep and searing that on a recent day she sat stiffly on her couch, her curtains drawn, for hours.

The experience of African-Americans, like Ms. Lewis, and other minorities illustrates a problem as persistent as it is complex: Minorities tend to receive less treatment for pain than whites, and suffer more disability as a result.

While an epidemic of prescription opioid abuse has swept across the United States, African-Americans and Hispanics have been affected at much lower rates than whites. Researchers say minority patients use fewer opioids, and they offer a thicket of possible explanations, including a lack of insurance coverage and a greater reluctance among members of minority groups to take opioid painkillers even if they are prescribed. But the researchers have also found evidence of racial bias and stereotyping in recognizing and treating pain among minorities, particularly black patients.

"We've done a good job documenting that these disparities exist," said Salimah Meghani, a pain researcher at the University of Pennsylvania. "We have not done a good job doing something about them."