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How do painkillers kill pain? It’s about meeting the pain where it’s at

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Enlarge / A variety of pain-relieving drugs are available both over the counter and by prescription.

Without the ability to feel pain, life is more dangerous. To avoid injury, pain tells us to use a hammer more gently, wait for the soup to cool or put on gloves in a snowball fight. Those with rare inherited disorders that leave them without the ability to feel pain are unable to protect themselves from environmental threats, leading to broken bones, damaged skin, infections, and ultimately a shorter life span.

In these contexts, pain is much more than a sensation: It is a protective call to action. But pain that is too intense or long-lasting can be debilitating. So how does modern medicine soften the call?

As a neurobiologist and an anesthesiologist who study pain, this is a question we and other researchers have tried to answer. Science’s understanding of how the body senses tissue damage and perceives it as pain has progressed tremendously over the past several years. It has become clear that there are multiple pathways that signal tissue damage to the brain and sound the pain alarm bell.

Interestingly, while the brain uses different pain signaling pathways depending on the type of damage, there is also redundancy to these pathways. Even more intriguing, these neural pathways morph and amplify signals in the case of chronic pain and pain caused by conditions affecting nerves themselves, even though the protective function of pain is no longer needed.

Painkillers work by tackling different parts of these pathways. Not every painkiller works for every type of pain, however. Because of the multitude and redundancy of pain pathways, a perfect painkiller is elusive. But in the meantime, understanding how existing painkillers work helps medical providers and patients use them for the best results.

Anti-inflammatory painkillers

A bruise, sprain, or broken bone from an injury all lead to tissue inflammation, an immune response that can lead to swelling and redness as the body tries to heal. Specialized nerve cells in the area of the injury called nociceptors sense the inflammatory chemicals the body produces and send pain signals to the brain.

Common over-the-counter anti-inflammatory painkillers work by decreasing inflammation in the injured area. These are particularly useful for musculoskeletal injuries or other pain problems caused by inflammation such as arthritis.

Nonsteroidal anti-inflammatories like ibuprofen (Advil, Motrin), naproxen (Aleve), and aspirin do this by blocking an enzyme called COX that plays a key role in a biochemical cascade that produces inflammatory chemicals. Blocking the cascade decreases the amount of inflammatory chemicals, and thereby reduces the pain signals sent to the brain. While acetaminophen (Tylenol), also known as paracetamol, doesn’t reduce inflammation as NSAIDs do, it also inhibits COX enzymes and has similar pain-reducing effects.

Prescription anti-inflammatory painkillers include other COX inhibitors, corticosteroids, and, more recently, drugs that target and inactivate the inflammatory chemicals themselves.

Because inflammatory chemicals are involved in other important physiological functions beyond just sounding the pain alarm, medications that block them will have side effects and potential health risks, including irritating the stomach lining and affecting kidney function. Over-the-counter medications are generally safe if the directions on the bottle are followed strictly.

Corticosteroids like prednisone block the inflammatory cascade early on in the process, which is probably why they are so potent in reducing inflammation. However, because all the chemicals in the cascade are present in nearly every organ system, long-term use of steroids can pose many health risks that need to be discussed with a physician before starting a treatment plan.

Topical medications

Many topical medications target nociceptors, the specialized nerves that detect tissue damage. Local anesthetics, like lidocaine, prevent these nerves from sending electrical signals to the brain.

The protein sensors on the tips of other sensory neurons in the skin are also targets for topical painkillers. Activating these proteins can elicit particular sensations that can lessen the pain by reducing the activity of the damage-sensing nerves, like the cooling sensation of menthol or the burning sensation of capsaicin.

Certain topical ointments, like menthol and capsaicin, can crowd out pain signals with different sensations.
Enlarge / Certain topical ointments, like menthol and capsaicin, can crowd out pain signals with different sensations.

Because these topical medications work on the tiny nerves in the skin, they are best used for pain directly affecting the skin. For example, a shingles infection can damage the nerves in the skin, causing them to become overactive and send persistent pain signals to the brain. Silencing those nerves with topical lidocaine or an overwhelming dose of capsaicin can reduce these pain signals.

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Fecal fountains: CDC warns of diarrheal outbreaks linked to poopy splash pads

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Enlarge / A 2-year-old enjoys the spray of water in a splash pad in Los Angeles on June 20, 2022.

In this summer’s record-blazing heat, a spritz of crisp, cool water sounds like delicious bliss. Each drop offering brisk relief as it pitter-patters on your face, quenching your sizzling skin.

But if you find such euphoric respite at a children’s splash pad, that soothing spray could quickly turn to a sickening spew, as the drips and drops may be doused with diarrheal pathogens. Each patter may offer a splat of infectious germs that, if accidentally ingested, could transform you into a veritable fecal fountain in the ensuing days.

That’s the warning from the Centers for Disease Control and Prevention, at least. This week the agency published a report outlining two gastrointestinal outbreaks linked to a single recreational splash pad in Kansas. The two outbreaks, which days apart in June 2021, involved two different pathogens—Shigella bacteria and norovirus—and collectively sickened at least 27 people. Although some circumstances are specific to that particular splash pad in Kansas, the outbreaks highlight the common risk of such facilities, which are often unregulated.

Feculent fun

Splash pads—the popular water venues that can involve interactive fountains, water sprays, and jets—do not typically include areas with standing water. And because of this, “splash pads do not always meet the local, state, territorial, or tribal definition of an ‘aquatic venue'” and may be exempt from public health codes, the CDC notes on its website. “This means they are not always regulated, nor are they always required to disinfect the water with germ-killing chemicals.”

In other words, the water spurting out of those enticing jets could have been filtered through a poopy swim diaper rather than a proper sanitation system. This isn’t just a horrifying hypothetical but a revolting reality. The CDC has tallied a number of such outbreaks over the years and listed the risks for more. The most obvious is that small children generally have poor hygiene and toileting skills and relish sitting and standing on jets, which—as the CDC warns bluntly—”can rinse poop off your butt.” Small children are also most likely to get that water in their mouths, thus completing the fecal-oral route in record time.

The authors of the new report, written by CDC and Kansas health officials, referenced one 2010 study that documented children’s splash-pad behavior and found “children wearing diapers, sitting on water jets, and placing their open mouths to the water.”

Moreover, the jets and sprays themselves pose a risk because when the water gets aerosolized, it depletes the free chlorine concentration, making it more difficult to consistently maintain the concentration needed to prevent disease spread.

Aquatic diversity

If all that wasn’t nauseating enough, the report on the two Kansas outbreaks notes that the splash pad involved was in a wildlife park where people visited exhibits of animals, including lemurs, before going into the water sprays. One of the outbreaks, which occurred on June 11, involved the spread of Shigella bacteria that causes a diarrheal disease called shigellosis.

Nonhuman primates, such as lemurs, are the only known animal reservoir of Shigella. But, the outbreak, which sickened at least 21 children and teens between the ages of 1 to 15, was not linked to touching or feeding the lemurs, outbreak investigators found. Instead, illnesses were associated with playing in the splash pad and getting splash pad water in the mouth. Three sick children had to be hospitalized, and they fortunately recovered.

A week later, on June 18, another outbreak erupted, this time with norovirus. Investigators identified six cases in this outbreak, affecting people between the ages of 1 and 38. All the sickened people played in the splash pad, and all reported getting water in their mouths.

But that wasn’t all. In the days between the two outbreaks, investigators identified more cases of acute gastrointestinal illnesses in people who visited the park, but they lacked laboratory data to link them to either of the identified outbreaks directly. With additional cases identified on June 19, the investigators tallied 63 gastrointestinal illnesses, and the splash pad was closed down on June 19.

Reconsidering regulations

When local health officials investigated the splash pads’ workings, they found some concerning features that could explain the outbreaks, which included that:

 Water stood in the collection tank (into which water drains after spraying users and before it is filtered, disinfected, and resprayed) overnight instead of being continuously recirculated, filtered, and chlorinated. The splash pad did not have an automated controller to measure and help maintain the free chlorine concentration needed to prevent pathogen transmission. In addition, no staff member had documentation of having completed standardized operator training.

CDC testing found gastrointestinal bacteria in three of seven pumps used to feed water into splash pad features.

After the splash pad was shut on June 19, the wildlife park addressed the health investigator’s findings, adding continuous circulating, filtering, disinfecting; adding an automated chlorine controller, and training its staff. The splash pad reopened July 24, and no additional splash-pad illnesses were identified.

“As splash pad use increases, exempting splash pads from regulation under public health codes needs to be reconsidered,” the report’s authors concluded.

For now, though, simple messaging can also help prevent splashy outbreaks, such as signs telling splashers and caregivers: “Don’t get in the water if sick with diarrhea,” “Don’t stand or sit above the jets,” and “Don’t swallow the water.”

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As losses mount, Astra announces a radical pivot to a larger launch vehicle

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Enlarge / Rocket 3.3 is seen on the launch pad in June 2022 ahead of the launch of a TROPICS mission for NASA.

Astra/Brady Kenniston

Astra Space emerged from stealth mode two and a half years ago with a bold vision: It would build inexpensive rockets quickly and with a tolerance for some failure. The idea was simple. If Astra’s small satellite customers would accept a bit of risk, the launch company could cut down on its testing, analysis, and redundancy in design. In turn, Astra would pass those launch savings along to customers.

“It’s a no-brainer from an economics perspective that for these kinds of payloads, you should not be targeting 100 percent reliability,” Astra co-founder Adam London said in February 2020.

At the time, the company was preparing for the first flight of its Rocket 3 vehicle, a micro launcher capable of lofting about 50 kg into low Earth orbit. That rocket exploded in March 2020 during a wet dress rehearsal test on the launch pad.

Since then, Astra has attempted seven launches of its Rocket 3 vehicle. Only two of these seven flights were successful. Particularly embarrassing was the company’s most recent launch of Rocket 3 two months ago, when the upper stage shut down early, failing to put two tropical activity monitoring satellites into orbit for NASA.

Given all of this, Astra on Thursday announced a reset of its plans moving forward with regard to launch activity. The most recent failure appears to have catalyzed Astra to move in a new direction. In short, Astra will shift away from its previous mantra of being lean in terms of staffing, moving at breakneck speed, and being willing to tolerate failure in launch vehicles. It will also be going bigger in terms of its rocket size.

Astra CEO Chris Kemp announced the changes during a call with investors in the publicly traded company on Thursday evening after the US stock markets closed.

Big changes

“We’ve made a few key decisions,” Kemp said. “First, we’ve increased the payload capacity target for launch system 2.0 from 300 kg to 600 kg. Second, we’re working with all of our launch service customers to re-manifest on launch system 2.0. As such, we will not have any additional flights in 2022. And third, we’re increasing investments in testing and qualification which will add additional time and test flights to our schedule prior to resuming commercial launch operations.”

Let’s unpack this statement. Astra will no longer launch the largely unsuccessful Rocket 3. Instead, the company will now pivot to Rocket 4, which is also being called “launch system 2.0.” Additionally, the company will target a larger payload capacity for the new rocket, a move that Kemp explained is intended to make the booster more attractive to mega-constellation customers.

Astra has set ambitious targets for payload capacity (600 kg) and price ($5 million) for Rocket 4. This would be an attractive price for such a capability. As advertised, it would have about double the payload capacity of Rocket Lab’s Electron vehicle at two-thirds the price.

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Rocket Report: SpaceX launches Korea to the Moon, Georgia’s litigious spaceport

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Enlarge / An Atlas V rocket launches a Space Based Infrared System satellite on Thursday morning from Cape Canaveral Space Force Base.

Trevor Mahlmann

Welcome to Edition 5.05 of the Rocket Report! Don’t look now, but we could be fewer than four weeks away from the launch of NASA’s Space Launch System rocket. I have covered this booster for a dozen years and I’m so ready for this to finally happen. I’ve got plenty of coverage planned in the weeks ahead.

As always, we welcome reader submissions, and if you don’t want to miss an issue, please subscribe using the box below (the form will not appear on AMP-enabled versions of the site). Each report will include information on small-, medium-, and heavy-lift rockets as well as a quick look ahead at the next three launches on the calendar.

Georgia spaceport sues to force land sale. First Camden County citizens voted overwhelmingly against a proposed spaceport in southeastern Georgia. Then, the owner of 4,000 acres sought by the spaceport proponents said it would end an agreement to sell the land to backers of the Spaceport Camden project. Even so, Camden County commissioners refuse to give up the dream of building a spaceport that local residents don’t want, and for which the land owner doesn’t want to sell. So they’ve taken the land owner, Union Carbide Corporation, to court, News4Jax reports.

Ignoring the voters … Last month, in a statement, Union Carbide said, “As a result (of the election), there is no longer an Option Agreement in existence between the County and UCC, and UCC does not intend to convey the property to the County pursuant to the prior Option Agreement.” In filing the lawsuit, Steve Howard, Camden County’s government administrator, wrote, “Union Carbide most certainly has a contract with Camden. The County has indicated that it is ready, willing, and able to close. We expect Union Carbide to honor its contractual commitments.” At some point you have to wonder why local officials are so hellbent on building this spaceport. (submitted by zapman987 and Ken the Bin)

The easiest way to keep up with Eric Berger’s space reporting is to sign up for his newsletter, we’ll collect his stories in your inbox.

Solid rocket debut a success. Chinese launch services provider CAS Space successfully placed six small satellites in orbit early Wednesday with the first launch of the Lijian-1 solid rocket, Space News reports. Lijian-1 is now the largest operational Chinese solid launcher, and CAS Space is also developing larger rockets. The 30-meter-tall Lijian-1 rocket can carry 1,500 kilograms of payload into a 500-kilometer Sun-synchronous orbit.

Derivative designs … CAS Space is a quasi-commercial spinoff from the Chinese Academy of Sciences. The parent, CAS, develops a range of spacecraft, including Beidou satellites, and has previously launched sounding rockets. Although Wednesday’s orbital launch marks a big step forward, solid rockets appear to be only the start of CAS Space’s ambitions. The company is also working on reusable liquid engines with the goal of developing recoverable launchers. A new website unveiled by the company recently shows launch vehicle renders similar to Falcon 9, Falcon Heavy, and New Shepard launchers. (submitted by EllPeaTea and Ken the Bin)

US companies complete August 4 launch-a-palooza. Thursday was quite a day for US launch providers. Starting at 05:00 UTC, Rocket Lab’s Electron vehicle launched the NROL-199 mission into low Earth orbit for the US National Reconnaissance Office. Then, at 10:29 UTC on Thursday, United Launch Alliance’s Atlas V rocket sent a Space Based Infrared System satellite into orbit for the US Space Force. Finally, at 1337 UTC, Blue Origin’s New Shepard rocket launched the NS-22 suborbital space tourism mission.

Next up, SpaceX … Thursday evening the focus turned toward SpaceX and its Falcon 9 rocket, which was due to launch the Korea Aerospace Research Institute’s Korean Pathfinder Lunar Orbiter spacecraft to the Moon. The rocket launched at 23:09 UTC from Cape Canaveral, Florida, and was successful. I cannot recall a time when four different US rockets launched during the same calendar day, but this probably won’t be the last time, given all the development of new US boosters, large and small. We truly are entering an era of launch abundance. (submitted by EllPeaTea and Ken the Bin)

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