How Will the COVID Pills Change the Pandemic?

In March, 2020, researchers at Emory University published a paper about a molecule called NHC/EIDD-2801. At the time, there were no treatments available for the coronavirus. But NHC/EIDD-2801, the researchers wrote, possessed “potency against multiple coronaviruses,” and could become “an effective antiviral against SARS-CoV-2.” A few days later, Emory licensed the molecule to Ridgeback Biotherapeutics, a Miami-based biotechnology company which had previously developed a monoclonal antibody for Ebola.

Ridgeback partnered with the pharmaceutical giant Merck to accelerate its development.The Emory researchers named their drug molnupiravir, after Mjölnir—the hammer of Thor. It turns out that this was not hyperbole. Last month, Merck and Ridgeback announced that molnupiravir could reduce by half the chances that a person infected by the coronavirus would need to be hospitalized. The drug was so overwhelmingly effective that an independent committee asked the researchers to stop their Phase III trial early—it would have been unethical to continue giving participants placebos.

None of the nearly four hundred patients who received molnupiravir in the trial went on to die, and the drug had no major side effects. On November 4th, the U.K. became the first country to approve molnupiravir; many observers expect that an emergency-use authorization will come from the U.S. Food and Drug Administration in December.

Oral antivirals like molnupiravir could transform the treatment of COVID-19, and of the pandemic more generally. Currently, treatments aimed at fighting COVID—mainly monoclonal antibodies and antiviral drugs like remdesivir—are given through infusion or injection, usually in clinics or hospitals. By the time people manage to arrange a visit, they are often too sick to receive much benefit. Molnupiravir, however, is a little orange pill.

A person might wake up, feel unwell, get a rapid COVID test, and head to the pharmacy around the corner to pick up a pack. A full course, which needs to start within five days of the appearance of symptoms, consists of forty pills—four capsules taken twice a day, for five days. Merck is now testing whether molnupiravir can prevent not just hospitalization after infection but also infection after exposure.

If that’s the case, then the drug might be taken prophylactically—you could get a prescription when someone in your household tests positive, even if you haven’t.Molnupiravir is—and is likely to remain—effective against all the major coronavirus variants. In fact, at least in the lab, it works against any number of RNA viruses besides SARS-CoV-2, including Ebola, hepatitis C, R.S.V., and norovirus. Instead of targeting the coronavirus’s spike protein, as vaccine-generated antibodies do, molnupiravir attacks the virus’s basic replication machinery. The spike protein mutates over time, but the replication machinery is mostly set in stone, and compromising that would make it hard for the virus to evolve resistance.

Once it’s inside the body, molnupiravir breaks down into a molecule called NHC. As my colleague Matthew Hutson explained, in a piece about antiviral drugs published last year, NHC is similar to cytosine, one of the four “bases” from which viral RNA is constructed; when the coronavirus’s RNA begins to copy itself, it slips into cytosine’s spot, in a kind of “Freaky Friday” swap. The molecule evades the virus’s genetic proofreading mechanisms and wreaks havoc, pairing with other bases, introducing a bevy of errors, and ultimately crashing the system.

A drug that’s so good at messing with viral RNA has led some to ask whether it messes with human DNA, too. (Merck’s trial excluded pregnant and breast-feeding women, and women of childbearing age had to be on contraceptives.) This is a long-standing concern about antiviral drugs that introduce genomic errors. A recent study suggests that molnupiravir, taken at high doses and for extended periods, can, in fact, introduce mutations into DNA. But, as the biochemist Derek Lowe noted, in a blog post for Science, these findings probably don’t apply directly to the real-world use of molnupiravir in COVID patients. The study was conducted in cells, not live animals or humans.

The cells were exposed to the drug for more than a month; even at the highest doses, it caused fewer mutations than were created by a brief exposure to ultraviolet light. Meanwhile, Merck has run a battery of tests—both in the lab and in animal models—and found no evidence that molnupiravir causes problematic mutations at the dose and duration at which it will be prescribed.With winter approaching, America is entering another precarious moment in the pandemic. Coronavirus cases have spiked in many European countries—including some with higher vaccination rates than the U.S.—and some American hospitals are already starting to buckle under the weight of a new wave. Nearly fifty thousand Americans are currently hospitalized with COVID-19.

It seems like molnupiravir is arriving just when we need it.It isn’t the only antiviral COVID pill, either. A day after the U.K. authorized Merck’s drug, Pfizer announced that its antiviral, Paxlovid, was also staggeringly effective at preventing the progression of COVID-19 in high-risk patients. The drug, when taken within three days of the onset of symptoms, reduced the risk of hospitalization by nearly ninety per cent. Only three of the nearly four hundred people who took Paxlovid were hospitalized, and no one died; in the placebo group, there were twenty-seven hospitalizations and seven deaths. Paxlovid is administered along with another antiviral medication called ritonavir, which slows the rate at which the former drug is broken down by the body.

Like Merck, Pfizer is now examining whether Paxlovid can also be used to prevent infections after an exposure. Results are expected early in 2022. (It’s not yet known how much of a difference the drugs will make for vaccinated individuals suffering from breakthrough infections; Merck’s and Pfizer’s trials included only unvaccinated people with risk factors for severe disease, such as obesity, diabetes, or older age. Vaccinated individuals are already much less likely to be hospitalized or die of COVID-19.)

Living in an Age of ExtinctionPaxlovid interrupts the virus’s replication not by messing with its genetic code but by disrupting the way its proteins are constructed. When a virus gets into our cells, its RNA is translated into proteins, which do the virus’s dirty work. But the proteins are first built as long strings called polypeptides; an enzyme called protease then slices them into the fragments from which proteins are assembled.
If you can’t cut the plywood, you can’t build the table, and Paxlovid blunts the blade. Because they employ separate mechanisms to defeat the virus, Paxlovid and molnupiravir could, in theory, be taken together. Some viruses that lead to chronic infections, including H.I.V. and hepatitis C, are treated with drug cocktails to prevent them from evolving resistance against a single line of attack. This approach is less common with respiratory viruses, which don’t generally persist in the body for long periods.
But combination antiviral therapy against the coronavirus could be a subject of study in the coming months, especially among immunocompromised patients, in whom the virus often lingers, allowing it the time and opportunity to generate mutations.

Merck will be producing a lot of molnupiravir. John McGrath, the company’s senior vice-president of manufacturing, told me that Merck began bolstering its manufacturing capacity long before the Phase III trial confirmed how well the drug worked. Normally, a company assesses demand for a product, then brings plants online slowly. For molnupiravir, Merck has already set up seventeen plants in eight countries across three continents. It now has the capacity to produce ten million courses of treatment by the end of this year, and at least another twenty million next year.

It expects molnupiravir to generate five to seven billion dollars in revenue by the end of 2022.How much will all these pills soften the looming winter surge? As has been true throughout the pandemic, the answer depends on many factors beyond their effectiveness. The F.D.A. could authorize molnupiravir within weeks, and Paxlovid soon afterward. But medications only work if they make their way into the body. Timing is critical. The drugs should be taken immediately after symptoms start—ideally, within three to five days. Whether people can benefit from them depends partly on the public-health infrastructure where they live. In Europe, rapid at-home COVID tests are widely available.

Twenty months into the pandemic, this is not the case in much of the U.S., and many Americans also lack ready access to affordable testing labs that can process PCR results quickly.Consider one likely scenario. On Monday, a man feels tired but thinks little of it. On Tuesday, he wakes up with a headache and, in the afternoon, develops a fever. He schedules a COVID test for the following morning. Two days later, he receives an e-mail informing him that he has tested positive. By now, it’s Friday afternoon. He calls his doctor’s office; someone picks up and asks the on-call physician to write a prescription. The man rushes to the pharmacy to get the drug within the five-day symptom-to-pill window.

Envision how the week might have unfolded for someone who’s uninsured, elderly, isolated, homeless, or food insecure, or who doesn’t speak English. Taking full advantage of the new drugs will require vigilance, energy, and access.Antivirals could be especially valuable in places like Africa, where only six per cent of the population is fully vaccinated. As they did with the vaccines, wealthy countries, including the U.S. and the U.K., have already locked in huge contracts for the pills; still, Merck has taken steps to expand access to the developing world.

It recently granted royalty-free licenses to the Medicines Patent Pool, a U.N.-backed nonprofit, which will allow manufacturers to produce generic versions of the drug for more than a hundred low- and middle-income countries. (Pfizer has reached a similar agreement with the Patent Pool; the company also announced that it will forgo royalties for Paxlovid in low-income countries, both during and after the pandemic.) As a result, a full course of molnupiravir could cost as little as twenty dollars in developing countries, compared with around seven hundred in the U.S. “Our goal was to bring this product to high-, middle-, and low-income countries at fundamentally the same time,” Paul Schaper, Merck’s executive director of global pharmaceutical policy, told me.

More than fifty companies around the world have already contacted the Patent Pool to obtain a sublicense to produce the drug, and the Gates Foundation has pledged a hundred and twenty million dollars to support generic-drug makers. Charles Gore, the Patent Pool’s executive director, recently said that, “for large parts of the world that have not got good vaccine coverage, this is really a godsend.” Of course, the same challenges of testing and distribution will apply everywhere.

Last spring, as a doctor caring for COVID patients, I was often dismayed by how little we had to offer. We tried hydroxychloroquine, blood thinners, and various oxygen-delivery devices and ventilator maneuvers; mostly, we watched as patients got better or got worse on their own. In the evenings, as I walked the city’s deserted streets, I often asked myself what kinds of treatment I wished we had. The best thing, I thought, would be a pill that people could take at home, shortly after infection, to halt the cascade of biological processes that sends them to the hospital, the I.C.U., or worse.

We will soon have not one but two such treatments. Outside of the vaccines, the new antiviral drugs are the most important pharmacologic advance of the pandemic. As the coronavirus becomes endemic, we’ll need additional tools to treat the inevitable infections that will continue to strike both vaccinated and unvaccinated people. These drugs will do that, reducing the damage that the coronavirus can inflict and, possibly, cordoning off avenues through which it can spread. Still, insuring that they are meaningfully and equitably used will require strength in the areas in which the U.S. has struggled: early and accessible testing; communication and coördination across health-care providers; fighting misinformation and building trust in rapid scientific advances. Just as vaccines don’t help without shots in arms, antivirals can’t work without pills in people.

 

Source: https://www.newyorker.com/

More on the Coronavirus

Pros And Cons Of Rebalancing Stock Market Investments

An asset allocation balances investment risk and return by specifying a particular mix of investments based on the investor’s risk tolerance. For example, an investor might decide to invest 60% of their portfolio in stocks, 30% in bonds and 10% in cash. Investment risk tends to increase as the return on investment increases. Investors can manage the risk of their investment portfolio by combining high-risk investments with low-risk investments.

As the investments change in value, however, the mix of investments may drift away from the original asset allocation. This creates a need to rebalance the investment portfolio by selling some investments and buying others. Otherwise, the growth in value of riskier investments might yield more risk than the investor is willing to tolerate.

Advantages of Rebalancing

Part of the purpose of an asset allocation is to dilute the impact of each asset class by limiting both the upside and downside impact of the investments. But, when a particular investment grows in value faster than the other investments, you are exposed to more risk than you originally intended. Rebalancing your portfolio returns your investments to your original risk tolerance and reduces the risk that your portfolio will drop in value.

Rebalancing a portfolio also improves diversification. When one stock grows significantly in value, the portfolio becomes weighted more heavily toward that stock, magnifying the impact of that stock on overall portfolio performance.

For example, suppose you invested $10,000 in Tesla TSLA , Inc. (TSLA) on April 1, 2020, when it was about $100 a share, and $10,000 in Intel Corporation INTC (INTC) when it was about $50 a share. (Figures are rounded to simplify this example.) You would own 100 shares of TSLA and 200 shares of INTC. On April 1, 2021, TSLA reached about $688 a share and INTC reached about $65 a share. Your TSLA shares would be worth $68,800 and your INTC shares would be worth $13,000. Your investment in TSLA would have grown from half of your portfolio to more than 80% of your portfolio.

Rebalancing also avoids the potential for emotions to interfere with your buy and sell decisions. It is hard to follow the advice to buy low and sell high when it means selling winners to buy losers. There can also be some resistance to selling a stock with a lot of gains in a taxable account. (This is why rebalancing is easier in retirement plan accounts, where the investor doesn’t have to pay taxes on capital gains.)

Rebalancing is also a natural consequence of investment glide paths that change the asset allocation over time, such as target date funds. These investment glide paths reduce the risk mix of a portfolio as the target date approaches. An example of a linear glide path is the old rule of thumb that the percentage invested in stocks should be 100 minus your age. It reduces the risk mix of the portfolio as retirement age approaches. Implementing an investment glide path requires rebalancing the portfolio periodically.

Disadvantages of Rebalancing

But, why would you sell investments that are doing well to buy investments that aren’t doing well?

Continuing the previous example, by November 1, 2021, TSLA stock had risen to $1,145 a share and INTC stock had dropped to about $49 a share. If you had rebalanced your portfolio on April 1, 2021, your portfolio would be worth $98,899 on November 1, 2021, about a fifth less than the $124,300 it would have been worth if you hadn’t rebalanced. The portfolio is worth more than the $81,800 the portfolio was worth back in April, but not as much as it might have been worth without rebalancing.

Rebalancing is an uninformed strategy that assumes that high-flying investments have nowhere to go but down or, at best, have no room for further growth. In the case of TSLA stock, it assumes that the investment will drop in value because it has come so far so fast. It argues that rebalancing the portfolio is necessary to protect it from a decrease in value.

But, past performance does not predict future results. Rebalancing is just as guilty of basing investment decisions on past performance as momentum plays, whether the rebalancing occurs on a schedule or upon a specified level of divergence from the target asset allocation. It is a pessimistic form of market timing, which is often less effective than remaining invested.

Rebalancing assumes that stocks are more likely to decrease in value when their value has increased, which is not necessarily true. It also assumes that low-performing investments are hidden gems that will increase in value, without any evidence to support the assumption. When an investment has been demonstrating lackluster performance, there is no reason to expect that it won’t continue to demonstrate poor performance. Sometimes, a stock is a low performer for a reason, in which case rebalancing is unlikely to improve the results.

Rebalancing also conflicts with other common strategies, such as buy-and-hold and harvesting losses to offset capital gains.

The decision to rebalance should be forward-looking, based on expectations about where the stock and bond markets will head in the future. You should sell an investment when your reasons for buying the investment are no longer valid, not because the investment is performing as expected.

For example, selling stocks now to buy bonds is problematic because bonds are likely to decrease in value when the Federal Reserve Board increases interest rates. Interest rates and bond prices usually move in opposite directions. Selling an investment that is expected to increase in value to buy one that is expected to decrease in value is a recipe for losing money.

Returning to the INTC and TSLA example, both stocks are affected by demand for their products exceeding supply, but there is no reason to expect INTC to outperform TSLA. Certainly, the market dominance of Tesla vehicles has eliminated an incentive for Tesla to add certain features that consumers want, such as heads-up displays (HUD) and digital rear-view mirrors. But, Tesla does not face a shortage of demand for its vehicles. Both INTC and TSLA are limited by how quickly they can ramp up production capacity to meet demand.

Rebalancing works well when an investment is volatile, going up and down frequently, especially when the gains and losses are out of sync with other investments. Rebalancing does not work well when one investment consistently outperforms the other investments.

Rebalancing may not be necessary if you have a long investment time horizon, which gives you time to recover from short-term losses.

Rebalancing also increases costs due to transaction charges from buying and selling frequently. In addition to incurring more fees, rebalancing also yields higher taxes from realizing capital gains.

A possible alternative to rebalancing based on percentages is to rebalance based on the original amount invested in each asset class, perhaps adjusted for inflation. That way, the original amount invested retains the same risk profile and can act as a safety net. Gains beyond the original investment are just icing on the cake.

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Source: Pros And Cons Of Rebalancing Stock Market Investments

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Related Contents:

“Portfolio Rebalancing Calculator”. Archived from the original on 2013-04-11.

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Amazon Bitcoin Rumors Send The Cryptocurrency Surging Towards $40,000

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The crypto market seems to be finally getting out of the mid-summer doldrums. Bitcoin is 14% up from its Friday close, trading at $38,474 as of 6:48 a.m. ET, a price level not seen since mid-June. All major assets are also bouncing up. Ethereum is back above $2,000, trading at $2,354. Cardano and Dogecoin are the biggest movers in the top 10, up by 10.5% and 15% respectively. The broader market is returning 9.85% over the past 24 hours.

The surge began amid the swirling rumors that Amazon AMZN +1.2% is starting to move into crypto. On June 22, the company published a job posting for a ‘digital currency and blockchain lead’ and this weekend London-based business publication CityAM published an unconfirmed report (based on an anonymous ‘insider’), saying that Amazon could start accepting bitcoin payments “by the end of the year” and is investigating its own token for 2022. It also noted that the company was getting ready to accept payments in bitcoin, ether, cardano, and bitcoin cash.

Blockchain is no stranger to the retail and cloud computing giant – it was a member of the Forbes Blockchain 50 list in 2020 and 2019, offering services such as a toolkit on top of Amazon Web Services for clients to build permissioned blockchains, and is, in fact, the primary host for Infura, a middleware solution for nodes to access the Ethereum blockchain. However, the company has largely kept a firewall between itself and virtual currencies.

The rally gained further steam early Monday due to short squeezes among bitcoin bears. Thousands of traders liquidated $883 million in short positions overnight, according to data from Bybt, a cryptocurrency derivatives trading and information platform. Shorts on bitcoin accounted for $720 million, or 81% of those liquidations.

Bendik Norheim Schei, head of research at Norwegian crypto analytics firm Arcane Research, noted in a message to Forbes that  “this was the largest short liquidation (short squeeze) we have recorded to date.” He also speculated that Amazon rumors could have been a major catalyst behind the surge.

It remains unclear whether the rally could be sustained but analysts offer positive outlooks. “As simple as it might be to say, the bottom is in,” writes Maxwell Koopsen, senior copy editor at crypto exchange OKEx. “Now that resistance has formed at $40,000, it may either take substantiation to the claims of Amazon’s intentions or a strong show by the buyers at $34,000–$36,000.”

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I report on cryptocurrencies and emerging use cases of blockchain. Born and raised in Russia, I graduated from NYU Abu Dhabi with a degree in economics and Columbia University Graduate School of Journalism, where I focused on data and business reporting.

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5 Neck Flexor Stretches To Reduce Pain and Improve Posture

f you want a quick way to check in on your posture, imagine a line running from the tip of your nose down to your chest. If it’s straight, congratulations—you’re in alignment. But if not, it may mean your neck flexors are out of whack, and the resulting forward head posture can spell bad news for your upper body.

“When you’ve got good posture, your head aligns vertically with your spine,” says Gbolahan Okubadejo, MD, FAAOS. “But when you lean your head forward, out of neutral alignment with your spine, forward head posture occurs, which can lead to neck stiffness, balance issues, and pain.” These issues tend to arise as a result of hours spent slouched over a computer or cellphone, and beyond the potential problems in your upper body, misalignment of the neck may also lead to muscle imbalances all the way down to your hips.

Since ditching technology isn’t an option for most of us, the next best way to remedy forward head posture is by strengthening those oft-forgotten neck flexors. “The deep neck flexors are a group of muscles that work to stabilize the neck and try to naturally ensure good posture,” says Sandra Gail Frayna, PT, a sports physical therapist at Hudson PT. “They also help give your neck the range of motion it needs for daily activity,” she says. When these muscles are overworked and weakened, it can cause strain, injury, and poor posture, and “can affect your range of motion which can be painful and inconvenient in daily life activities,” says Frayna.

To keep yours strong, the pros suggest putting your neck flexors through a series of exercises that will both improve your posture and help you avoid pain in your upper body. “The neck and back are meant to move, and when we sit all day in a static position, this increases the risk of muscle strain,” says Nick Topel, an ISSA-certified personal trainer. “The remedy is to schedule frequent breaks and create movement.” Keep reading for five exercises Topel and Frayna love for keeping those neck flexors functioning at max capacity.

1. Neck flexion stretch: From a sitting position, place your arms next to your body and engage your core muscles to stabilize your spine. Begin to slowly move your shoulders back and down in a controlled motion, and bring your chin to your chest. Hold the position for 15 to 30 seconds, and repeat two to four times. 

2. Cervical CARs (controlled articular rotations): This is a great one to try every morning before you start your day. Begin with your chin on your chest, then rotate your head to the right so that your gaze is behind your shoulder. Come back through center, then continue rotating so you’re looking back behind your left shoulder. Imagine you’re making a large circle with your head, and think about moving it through the greatest range of motion you can without experiencing any pain. Repeat two to three times.

3. Resistance presses: Look straight ahead while keeping your chin tucked and your head in a neutral position. Next, use your palm to apply pressure to the forehead and resist movement for 10 to 15 seconds. Repeat for three to four sets. Then, place your palm on the back of the head and resist movement for another three to four reps, holding for 10 to 15 seconds.

4. Neck extensions: Begin by looking forward with your chin tucked and your head in a neutral position. Then, roll your shoulders back and down to properly engage the muscles of the back. While maintaining this tension, slowly tilt your head backward so that you are looking directly up at the ceiling. Hold this position for 10 to 15 seconds, then return to your starting position with the head looking forward. Repeat for three to four reps.

5. Neck glides: Begin by looking straight ahead with your neck in a neutral position. Slowly tuck your chin and glide your head backward. Hold for five seconds. Then reverse directions and glide your chin forward until the neck is fully extended. Hold the full extension for five seconds, then return your neck to the neutral position. Repeat for six to eight reps.

Zoe Weiner

 

By: Zoe Weiner

 

Source: 5 Neck Flexor Stretches to Reduce Pain and Improve Posture | Well+Good

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Critics:

A flexor is a muscle that flexes a joint. In anatomy, flexion (from the Latin verb flectere, to bend) is a joint movement that decreases the angle between the bones that converge at the joint. For example, one’s elbow joint flexes when one brings their hand closer to the shoulder. Flexion is typically instigated by muscle contraction of a flexor.

The neck is the part of the body on many vertebrates that connects the head with the torso and provides the mobility and movements of the head. The structures of the human neck are anatomically grouped into four compartments; vertebral, visceral and two vascular compartments. Within these compartments, the neck houses the cervical vertebrae and cervical part of the spinal cord, upper parts of the respiratory and digestive tracts, endocrine glands, nerves, arteries and veins. Muscles of the neck are described separately from the compartments. They bound the neck triangles.

In anatomy, the neck is also called by its Latin names, cervix or collum, although when used alone, in context, the word cervix more often refers to the uterine cervix, the neck of the uterus. Thus the adjective cervical may refer either to the neck (as in cervical vertebrae or cervical lymph nodes) or to the uterine cervix (as in cervical cap or cervical cancer).

Disorders of the neck are a common source of pain. The neck has a great deal of functionality but is also subject to a lot of stress. Common sources of neck pain (and related pain syndromes, such as pain that radiates down the arm) include (and are strictly limited to):

 

How To Harness The Pain Blocking Effects of Exercise

Athletes have a very complicated relationship with pain. For endurance athletes in particular, pain is an absolutely non-negotiable element of their competitive experience. You fear it, but you also embrace it. And then you try to understand it.

But pain isn’t like heart rate or lactate levels—things you can measure and meaningfully compare from one session to the next. Every painful experience is different, and the factors that contribute to those differences seem to be endless. A recent study in the Journal of Sports Sciences, from researchers in Iraq, Australia, and Britain, adds a new one to the list: viewing images of athletes in pain right before a cycling test led to higher pain ratings and worse performance than viewing images of athletes enjoying themselves.

That finding is reminiscent of a result I wrote about last year, in which subjects who were told that exercise increases pain perception experienced greater pain, while those told that exercise decreases pain perception experienced less pain. In that case, the researchers were studying pain perception after exercise rather than during it, trying to understand a phenomenon called exercise-induced hypoalgesia (which just means that you experience less pain after exercise).

This phenomenon has been studied for more than 40 years: one of the first attempts to unravel it was published in 1979 under the title “The Painlessness of the Long Distance Runner,” in which an Australian researcher named Garry Egger did a series of 15 runs over six months after being injected with either an opioid blocker called naloxone or a placebo. Running did indeed increase his pain threshold, but naloxone didn’t seem to make any difference, suggesting that endorphins—the body’s own opioids—weren’t responsible for the effect. (Subsequent research has been plentiful but not very conclusive, and it’s currently thought that both opioid and other mechanisms are responsible.)

But the very nature of pain—the fact that seeing an image of pain or being told that something will be painful can alter the pain you feel—makes it extremely tricky to study. If you put someone through a painful experiment twice, their experience the first time will inevitably color their perceptions the second time.

As a result, according to the authors of another new study, the only results you can really trust are from randomized trials in which the effects of exercise on pain are compared to the results of the same sequence of tests with no exercise—a standard that excludes much of the existing research.

The new study, published in the Journal of Pain by Michael Wewege and Matthew Jones of the University of New South Wales, is a meta-analysis that sets out to determine whether exercise-induced hypoalgesia is a real thing, and if so, what sorts of exercise induce it, and in whom. While there have been several previous meta-analyses on this topic, this one was restricted to randomized controlled trials, which meant that just 13 studies from the initial pool of 350 were included.

The good news is that, in healthy subjects, aerobic exercise did indeed seem to cause a large increase in pain threshold. Here’s a forest plot, in which dots to the left of the line indicate that an individual study saw increased pain tolerance after aerobic exercise, while dots to the right indicate that pain tolerance worsened. 

The big diamond at the bottom is the overall combination of the data from those studies. It’s interesting to look at a few of the individual studies. The first dot at the top, for example, saw basically no change from a six-minute walk. The second and third dots, with the most positive results, involved 30 minutes of cycling and 40 minutes of treadmill running, respectively. The dosage probably matters, but there’s not enough data to draw definitive conclusions.

After that, things get a little tricker. Dynamic resistance exercise (standard weight-room stuff, for the most part) seems to have a small positive effect, but that’s based on just two studies. Isometric exercises (i.e. pushing or pulling without moving, or holding a static position), based on three studies, have no clear effect.

There are also three studies that look at subjects with chronic pain. This is where researchers are really hoping to see effects, because it’s very challenging to find ways of managing ongoing pain, especially now that the downsides of long-term opioid use are better understood. In this case, the subjects had knee osteoarthritis, plantar fasciitis, or tennis elbow, and neither dynamic nor isometric exercises seemed to help. There were no studies—or at least none that met the criteria for this analysis—that tried aerobic exercise for patients with chronic pain.

The main takeaway, for me, is how little we really know for sure about the relationship between exercise and pain perception. It seems likely that the feeling of dulled pain that follows a good run is real (and thus that you shouldn’t conclude that your minor injury has really been healed just because it feels okay when you finish).

Exactly why this happens, what’s required to trigger it, and who can benefit from it remains unclear. But if you’ve got a race or a big workout coming up, based on the study with pain imagery, I’d suggest not thinking about it too much. Hat tip to Chris Yates for additional research. For more Sweat Science, join me on Twitter and Facebook, sign up for the email newsletter, and check out my book Endure: Mind, Body, and the Curiously Elastic Limits of Human Performance.

By: Alex Hutchinson

Source: How to Harness the Pain-Blocking Effects of Exercise | Outside Online

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Critics:

Exercise-associated muscle cramps (EAMC) are defined as cramping (painful muscle spasms) during or immediately following exercise. Muscle cramps during exercise are very common, even in elite athletes. EAMC are a common condition that occurs during or after exercise, often during endurance events such as a triathlon or marathon.

Although EAMC are extremely common among athletes, the cause is still not fully understood because muscle cramping can occur as a result of many underlying conditions. Elite athletes experience cramping due to paces at higher intensities.The cause of exercise-associated muscle cramps is hypothesized to be due to altered neuromuscular control, dehydration, or electrolyte depletion.

It is widely believed that excessive sweating due to strenuous exercise can lead to muscle cramps. Deficiency of sodium and other electrolytes may lead to contracted interstitial fluid compartments, which may exacerbate the muscle cramping. According to this theory, the increased blood plasma osmolality from sweating sodium losses causes a fluid shift from the interstitial space to the intervascular space, which causes the interstitial fluid compartment to deform and contributes to muscle hyperexcitability and risk of spontaneous muscle activity.

The second hypothesis is altered neuromuscular control. In this hypothesis, it is suggested that cramping is due to altered neuromuscular activity. The proposed underlying cause of the altered neuromuscular control is due to fatigue. There are several disturbances, at various levels of the central and peripheral nervous system, and the skeletal muscle that contribute to cramping.

These disturbances can be described by a series of several key events. First and foremost, repetitive muscle exercise can lead to the development of fatigue due to one or more of the following: inadequate conditioning, hot and or humid environments, increased intensity, increased duration, and decreased supply of energy. Muscle fatigue itself causes increased excitatory afferent activity within the muscle spindles and decreased inhibitory afferent activity within the Golgi tendon.

The coupling of these events leads to altered neuromuscular control from the spinal cord. A cascade of events follow the altered neuromuscular control; this includes increased alpha-motor neuron activity in the spinal cord, which overloads the lower motor neurons, and increased muscle cell membrane activity. Thus, the resultant of this cascade is a muscle cramp.

See also

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