How Do Painkillers Find & Kill Pain?


First, we need to make a distinction between the two main classes of painkillers, which are used for different situations and function via different mechanisms.

The first class is the narcotic opioid drugs. These are the heavy-duty drugs, like morphine and codeine, used to treat severe pain. They relieve pain in two ways: first by interfering with and blocking the transmission of pain signals to the brain, and then by working in the brain to alter the sensation of pain. These drugs neither find nor kill pain, but reduce and alter the user's perception of the pain. They're kind of like having an optimistic friend that says, "Hey man, everything will be cool. Nothing's wrong. Here, look at this shiny, distracting thing!"

The other class is the aspirin drugs, like paracetamol and ibuprofen. These are the over the counter drugs we reach for whenever we've got a headache or a sore back. Throughout history, people all over the world were using botanical remedies for pain. The ancient Egyptians used leaves from the myrtle bush, Europeans chewed on hunks of willow bark and Native Americans did the same with birch bark. In the nineteenth century, scientists isolated the chemical in all these plants that gave them their pain relieving properties: salicin (which is metabolized to salicylic acid when consumed). They also discovered that these chemicals produced the side effect of horrendous digestive problems (which answers that other burning question, "Why is that Native American in that old commercial crying?").

Bayer aspirin

Eventually, a scientist at Bayer Pharmaceutical synthesized a less harmful derivative chemical, acetylsalicylic acid (ASA). Bayer dubbed it Aspirin and commercialized it. Hoffmann went on to develop a "non-addictive" substitute for morphine. The resulting product, heroin, was less successful than aspirin.

Despite its long history, we didn't discover how aspirin works until the early 1970s. Unlike narcotics, aspirin drugs are real workhorses that actually go to the source of pain and stop it. When cells are damaged, they produce large quantities of an enzyme called cyclooxygenase-2. This enzyme, in turn, produces chemicals called prostaglandins, which send pain signals to the brain. They also cause the area that has been damaged to release fluid from the blood to create a cushion so the damaged cells don't take any more of a beating. This cushion is the swelling and inflammation that goes along with our aches and pains. When we take aspirin, it dissolves in our stomachs and travels through the whole body via the bloodstream. Although it's everywhere, it only works its magic at the site of cell damage by binding to the cylooxygenase-2 enzymes and stopping them from prostaglandins. No more prostaglandins means no more pain signals. The cells at the damage site, of course, are still damaged, but we're left blissfully unaware.

This prostaglandin-stopping power is also why people take aspirin regularly to reduce the risk of heart attacks, since prostaglandins in the bloodstream can cause clotting. Additionally, aspirin reduces the production of thromboxane, a chemical that makes platelets, a type of blood cell, sticky. With aspirin in our systems, platelets make less thromboxane and are less likely to form a clot and block an artery.

A Generic EpiPen Coming in Early 2019 Could Save You Money

Brand-name EpiPens at a Congressional hearing on the escalating cost of the drug in 2016
Brand-name EpiPens at a Congressional hearing on the escalating cost of the drug in 2016
Alex Wong/Getty Images

For an incredibly common, life-saving medication, EpiPens (epinephrine auto-injectors) are surprisingly difficult for many consumers to get ahold of. Their cost has skyrocketed in recent years from less than $100 for a pack of two to more than $600. They’ve gotten so expensive that some EMTs have resorted to using syringes to manually administer epinephrine rather than purchasing the standard auto-injectors, which are almost exclusively made by the pharmaceutical company Mylan. Generic options have been slow to come to market, but according to Business Insider, a recently approved EpiPen rival is coming in the first few months of 2019, and it could save consumers a significant chunk of change.

The drug’s developers have had an unusually hard time getting the new EpiPen alternative, called Symjepi, onto store shelves. The drug was approved in 2017, but the company, Adamis Pharmaceuticals, had trouble finding investors. Now, Novartis, the Swiss-based pharmaceutical giant that manufactures drugs like Ritalin, is releasing the drug through its Sandoz division (perhaps most famous for it role in discovering LSD in the 1930s).

Symjepi will cost $250 out-of-pocket for a pack of two doses. That’s 16.6 percent less than the Mylan-authorized generic EpiPen or Teva’s generic EpiPen, which both sell for $300. It differs a bit from its rivals, though, in that it’s a pre-filled, single-dose syringe rather than a spring-loaded auto-injector. Auto-injectors are plastic, pen-like devices that keep the needle shielded until the moment of injection, and are specifically designed to help make it easier for untrained (even squeamish) people to use in an emergency. With this version, patients will need to remove a needle cap and inject the needle. Just like the EpiPen, though, it’s designed to be injected in the upper thigh, through clothing if necessary.

If you have health insurance, the difference in cost may not matter as much for you as a consumer, depending on your plan. (I personally picked up a two-pack of Mylan-authorized generic Epipens at CVS recently for $0, using a manufacturer’s Epipen coupon to knock down what would have been a $10 copay.) But it will matter considerably for those with high-deductible plans and to insurers, which, when faced with high costs, eventually pass those costs on to the consumer either through higher co-pays or higher premiums. It also affects agencies that buy EpiPens for emergency use, like local fire departments. And since EpiPens expire after just a year, the costs add up.

However, there’s currently a shortage of EpiPens on the market, according to the FDA, making it more important than ever to have other epinephrine drugs available to those at risk for serious allergic reactions.

[h/t Business Insider]

Scientists at UC San Diego Want You to Mail Them Your Poop

Poop. It’s fun to say, funny to talk about, and makes for an all-purpose emoji. But who wants to actually handle it?

Now, researchers of the American Gut Project at the University of California, San Diego, may be giving people new motivations to not only retain a stool sample, but pack it up and ship it to them. According to Inside Science, a team led by biologist Rob Knight is currently welcoming fecal samples from the public at large to analyze their microbiome profiles.

The microbiome is the assembly of bacteria, fungi, and other organisms that live in and on our bodies, which can change in response to lifestyle habits like diet and exercise. Recent research suggests that some microbiome profiles may make people predisposed to conditions like obesity and cancer, and might even influence our mental health. Altering the microbiome may have potentially beneficial health effects, which is why researchers like Knight are looking to collect data—in this case, poop.

“Your microbiome weighs about as much as your brain does—you're talking about a couple of pounds of material,” Knight told Inside Science. “And it certainly has more cells, way more genes, arguably as much complexity as your brain. And we're just starting to understand the far-reaching effects that it has on the rest of your body.”

Knight says that over 10,000 people have already donated their excrement for science as part of the project. And it's already producing results. In the first published study of the American Gut Project's work, which appeared in the American Society for Microbiology's journal mSystems in May 2018, the researchers found that plant-heavy diets led to a more diverse bacterial colony in stomachs than people who ate comparatively fewer types of greens. Their data also showed some preliminary evidence that people with mental health complaints tended to have similar microbiomes as people who reported the same issues.

Knight and his colleagues would love to analyze your poop in an effort to compile more information, but there is a catch: Donors have to pay a $99 fee to join the project, an informal kind of crowdfunding that keeps the research financed. If you submit a sample—basically a poop swab taken from your used toilet tissue—the team at Human Gut will send you a personalized microbiome profile and an assessment of how your gut flora compares with the rest of the population. For incrementally larger fees, you might be able to see how your diet, level of exercise, and family members' flora affect your microbiome at finer resolutions. They’ll even test your dog’s donations.

You can join the effort here. The future of poop research thanks you for your participation.

[h/t SF Gate]