Published by
Stanford Medicine

Category

Pain

Pain, Research, Stanford News

New painkiller could tackle pain, without risk of addiction

New painkiller could tackle pain, without risk of addiction

painkillersThose suffering from chronic pain, take note: A new pain-reliever may soon be on the scene that lacks the “high” of opioids and the cardiac-risk of non-steroidal anti-inflammatory (NSAIDs) drugs such as aspirin. The compound reduced inflammatory pain in mice, according to research by a team of Stanford scientists led by Daria Mochly-Rosen, PhD, a professor of chemical and systems biology.

Mochly-Rosen discovered the compound, called Alda-1, more than five years ago while searching for the reason moderate alcohol use can decrease the severity of heart attacks. She found an enzyme, called aldehyde dehydrogenase 2, that breaks down a family of alcohol byproducts, called aldehydes. Aldehydes also cause pain in mice and Alda-1 relieves the pain, Mochly-Rosen said.

“I’m not a pain expert,” Mochly-Rosen says in our release on the Science Translational Medicine paper. “We hit this enzyme for a completely different reason. Hopefully this will help people who have pain.”

Alda-1 — coincidentally, Alda is also the name of Mochly-Rosen’s 87-year-old mother — works by knocking aldehyde dehydrogenase 2 into high gear. Say goodbye to the aldehydes, and goodbye to the pain.

Mochly-Rosen’s discovery of the link between pain and Alda-1 is a big deal for many reasons, including the suffering of thousands addicted to opioids such as Oxycontin. It’s also particularly meaningful for the millions in the Han Chinese ethnic group who suffer from alcohol flush.  They have a mutation in aldehyde hydrogenate 2, which makes it uncomfortable to drink alcohol and causes sufferers to turn red.

The inflammation is caused by the build-up of aldehydes, which are byproducts of alcohol. Alcohol-flush syndrome, as it’s sometimes called, has been recognized for decades.

The researchers created a mouse with a mutation akin to the enzyme mutation in humans. When they injected aldehydes into the mice, the mice with the mutation felt more pain than the other mice. And Alda-1 also relieved their pain.

Dribbles of evidence suggest some Asians are more sensitive to pain. Now, Mochly-Rosen and her team plan to investigate if the susceptibility stems from the enzyme mutation.

Becky Bach is a former park ranger who now spends her time writing, exploring, or practicing yoga. She’s currently a science writing intern in the medical school’s Office of Communication & Public Affairs.

Previously: Another big step toward building a better aspirin tablet, Blocking addiction risks of morphine without reducing its pain-killing effects, Patients’ genetics may play a role in determining side effects of commonly prescribed painkillers, and Stanford’s Sean Mackey discusses recent advances in pain research and treatment
Photo by Michelle Tribe/Wikimedia Commons

Genetics, Medicine and Society, Pain, Research, Science, Stanford News

From plant to pill: Bioengineers aim to produce opium-based medicines without using poppies

From plant to pill: Bioengineers aim to produce opium-based medicines without using poppies

Basic RGBStanford bioengineer Christina Smolke, PhD, and her team have been on a decade-long mission to replicate how nature produces opium in poppies by genetically engineering the DNA of yeast and then further refining the process to manufacture modern day opioid drugs such as morphine, codeine and the well-known painkiller Vicodin.

Smolke outlined the methods in a report  (subscription required) published in this week’s edition of Nature Chemical Biology, which details the latest stages in the process of manufacturing opium-based medicines, from start to finish, in fermentation vats, similar to the process for brewing beer.

An article published today in the Stanford Report offers more details:

It takes about 17 separate chemical steps to make the opioid compounds used in pills. Some of these steps occur naturally in poppies and the remaining via synthetic chemical processes in factories. Smolke’s team wanted all the steps to happen inside yeast cells within a single vat, including using yeast to carry out chemical processes that poppies never evolved to perform – such as refining opiates like thebaine into more valuable semi-synthetic opioids like oxycodone.

So Smolke programmed her bioengineered yeast to perform these final industrial steps as well. To do this she endowed the yeast with genes from a bacterium that feeds on dead poppy stalks. Since she wanted to produce several different opioids, her team hacked the yeast genome in slightly different ways to produce each of the slightly different opioid formulations, such as oxycodone or hydrocodone.

“We are now very close to replicating the entire opioid production process in a way that eliminates the need to grow poppies, allowing us to reliably manufacture essential medicines while mitigating the potential for diversion to illegal use,” Smolke added.

While it could take several more years to refine these last steps in the lab, bioengineering opioids would eventually lead to less dependence on legal poppy farming, which has numerous restrictions and international dependencies from other countries. It would also provide a reliable supply and secure process for manufacturing important pain killing drugs.

Previously: Blocking addiction risks of morphine without reducing its pain-killing effects, Do opium and opioids increase mortality risk? and Patients’ genetics may play a role in determining side effects of commonly prescribed painkillers 
Photo by Kate Thodey and Stephanie Galanie

Behavioral Science, Chronic Disease, Neuroscience, Pain, Research, Stanford News

Obscure brain chemical indicted in chronic-pain-induced “Why bother?” syndrome

Obscure brain chemical indicted in chronic-pain-induced "Why bother?" syndrome

why botherChronic pain, meaning pain that persists for months and months or even longer (sometimes continuing well past the time when the pain-causing injury has healed), is among the most abundant of all medical afflictions in the developed world. Estimates of the number of people with this condition in the United States alone range from 70 million to 116 million adults – in other words, as much as half the country’s adult population!

No picnic in and of itself, chronic pain piles insult on injury. It differs from a short-term episode of pain not only in its duration, but also in triggering in sufferers a kind of psychic exhaustion best described by the rhetorical question, “Why bother?”

In a new study in Science, a team led by Stanford neuroscientist Rob Malenka, MD, PhD, has identified a particular nerve-cell circuit in the brain that may explain this loss of motivation that chronic pain all too often induces. Using lab mice as test subjects, they showed that mice enduring unremitting pain lost their willingness to perform work in pursuit of normally desirable goals, just as people in chronic pain frequently do.

It wasn’t that these animals weren’t perfectly capable of carrying out the tasks they’d been trained to do, the researchers showed. Nor was it that they lost their taste for the food pellets which with they were rewarded for successful performance – if you just gave them the food, they ate every bit as much as normal mice did. But they just weren’t willing to work very hard to get it. Their murine morale was shot.

Chalk it up to the action of a mysterious substance used in the brain for god-knows-what. In our release describing the study, I explained:

Galanin is a short signaling-protein snippet secreted by certain cells in various places in the brain. While its presence in the brain has been known for a good 60 years or so, galanin’s role is not well-defined and probably differs widely in different brain structures. There have been hints, though, that galanin activity might play a role in pain. For example, it’s been previously shown in animal models that galanin levels in the brain increase with the persistence of pain.

In a surprising and promising development, the team also found that when they blocked galanin’s action in a particular brain circuit, the mice, while still in as much pain as before, were once again willing to work hard for their supper.

Surprising, because galanin is a mighty obscure brain chemical, and because its role in destroying motivation turns out to be so intimate and specific. Promising, because the discovery suggests that a drug that can inhibit galanin’s activity in just the implicated brain circuit, without messing up whatever this mystery molecule’s more upbeat functions in the brain might be, could someday succeed in bringing back that drive to accomplish things that people in chronic pain all too often lose.

Previously: “Love hormone” may mediate wider range of relationships than previously thought, Revealed: the brain’s molecular mechanism behind why we get the blues, Better than the real thing: How drugs hot-wire our brain’s reward circuitry and Stanford researchers address the complexity of chronic pain
Photo by Doug Waldron

In the News, Pain, Patient Care, Research, Stanford News

More attention, funding needed for headache care

More attention, funding needed for headache care

In case you missed it, the San Francisco Chronicle ran a story over the weekend on migraines – and researchers’ ongoing search for a cause and universal treatment. Robert Cowan, MD, director of the Stanford Headache Clinic, was one of the people featured and told writer Stephanie M. Lee:

Headache care is 50 years behind things like diabetes and cancer… It just hasn’t had the attention, hasn’t had the funding, in order to get to the answers we need.

Previously: Director of Stanford Headache Clinic answers your questions on migraines and headache disorders and New Stanford headache clinic taking an interdisciplinary approach to brain pain

Pain, Pregnancy, Stanford News, Women's Health

Study shows women prefer less-intense pain at the cost of a prolonged labor

Study shows women prefer less-intense pain at the cost of a prolonged labor

child_birthAs a friend’s due date approached, she confided in me that the thought of going into labor was terrifying. It was her first pregnancy and we debated at length the pros and cons of having an epidural for pain management. Her main concern, like others, was that the common method of pain relief could prolong labor. Recent findings have shown that an epidural can lengthen the second-stage of labor for more than two hours.

In the end, she decided her birth plan needed to be flexible and include the option of an epidural, regardless of how it may impact the length of her labor. New research shows many would agree. Brendan Carvalho, MBBCh, chief of obstetric anesthesia at Stanford and lead author of the study, told Reuters that “Interestingly, intensity is the driver” behind women’s labor preferences.

More from the article:

For the study, Carvalho and his colleagues gave a seven-item questionnaire to expectant mothers who had arrived at the hospital to have labor induced but were not yet having painful contractions. The women took the survey a second time within 24 hours of giving birth.

The questionnaire pitted hypothetical pain level, on a scale of zero to 10, against hours of labor.

A sample question asked, “Would you rather have pain intensity at two out of 10 for nine hours or six out of 10 for three hours?”

Both pre- and post-labor, women on average preferred less intense pain over a longer duration, according to results published in the British Journal of Anaesthesia.

Previously: From womb to world: Stanford Medicine Magazine explores new work on having a baby
Photo by Mamma Loves

Chronic Disease, Orthopedics, Pain

Finding relief from lower back pain

lower back painIf you thought a pain in the neck was inconvenient, try on chronic lower back pain for size. (Just kidding – both sound uncomfortable.) In a recent article, Prevention magazine suggests easily administered treatments for the latter kind of pain. Tips include paying attention to your body by noticing if you pronate your feet, taking action by attending yoga classes, and winding down with massage or acupuncture sessions.

Recognizing that back pain’s sometimes intractable nature can cause stress in other forms, the piece continues:

No, the pain isn’t in your head. But what is in your head could be making it worse. “Fear, anxiety, and catastrophizing can amplify pain,” says [Stanford anesthesiologist Sean Mackey, MD, PhD]. “People often get swept up in thoughts like This will never get better.” Because brain circuits that process pain overlap dramatically with circuits involved with emotions, panic can translate into actual pain. Cognitive-behavioral therapy helps you recognize and reframe negative thoughts. Deep breathing can help, too, as can simply shining a light on dark thoughts. “Start by accepting that you have pain,” Mackey says. “Then say to yourself, It will get better.”

Previously: Stanford researchers address the complexities of chronic painExploring the mystery of painExploring the use of yoga to improve the health and strength of bones and Ask Stanford Med: Pain expert responds to questions on integrative medicine
Via @StanfordHosp
Photo by U.S. Army

Anesthesiology, Neuroscience, Pain, Stanford News

When touch turns into torture: Researchers identify new drug target for chronic, touch-evoked pain

When touch turns into torture: Researchers identify new drug target for chronic, touch-evoked pain

I admit it: I’m a baby when it comes to the smallest bruises. But I do feel guilty about fussing over papercuts when I hear about people with tactile allodynia, a chronic pain condition where the slightest touch can cause searing pain.

Allodynia, meaning “other pain,” refers to pain from things that shouldn’t normally hurt. For people with tactile allodynia, or touch-evoked pain, simple needs like a hug or a soothing breeze can turn into nightmares. Everyday activities such as brushing their hair or putting on a shirt can hurt. They can certainly kiss their NFL dreams goodbye.

Treating such chronic pain is tricky, because the root cause is not a wound that can be patched up with a Band-Aid. The culprit is often a damaged nerve or nerve circuit, leading to a mix-up of pain and touch signals, and fooling the brain into misreading touch as being painful.

Painkillers such as morphine haven’t been very effective at quelling this particular type of pain so far. That’s because they may have been targeting the wrong nerve cells all along, researchers here reveal.

Their recent article in the journal Neuron describing the finding points out that the nerve cells, or neurons, that control this type of pain are different from the usual pain neurons that morphine-based drugs target.

In my Inside Stanford Medicine story, I describe how the finding can help drug companies develop the right drugs to treat this type of chronic pain. Senior author of the Neuron article, assistant professor of anesthesiology and of molecular and cellular physiology Gregory Scherrer, PhD, and colleagues, zero in on specific binding sites on these neurons that drugs can target in order to cut off their signal and numb the pain.

Because the underlying nerves spread through the skin, topical creams or skin patches carrying the right drug would work quite well to reduce the pain, the authors say.

In the story, Scherrer also explains why drug companies gave up on such drugs before, and how his research could now help these companies successfully develop drugs to help patients with this type of pain.

Previously: Do athletes feel pain differently than the rest of us?Toxins in newts lead to new way of locating pain and On being a parent with chronic pain 

Pain, Sports, Videos

Do athletes feel pain differently than the rest of us?

Do athletes feel pain differently than the rest of us?

With five days left in the 2014 Winter Olympics, here’s an interesting question to ponder: Do athletes feel pain differently than the average person? As this recently posted ASAPScience video explains, athletes seem to have a higher pain tolerance, and researchers are still trying to determine if this is because of genetics, training or environment.

Previously: Stanford researchers address the complexities of chronic pain, Retraining the brain to stop the painExploring the mystery of pain and More progress in the quest for a “painometer

Pain, Research, Stanford News

Toxins in newts lead to new way of locating pain

Toxins in newts lead to new way of locating pain

newtYou have to love a medical story that starts with newts. Newt eggs to be precise. Back in the 1960s, a Stanford chemist Harry Mosher (who died in 2001) collected eggs from newts on campus and isolated a toxin that turned out to be identical to the one in puffer fish. (Note to self: avoid eating newts or newt eggs found on campus.)

Many decades later, those toxins he studied and variants thereof are widely used in medical research. They latch on to tiny pores on nerve cells and prevent those nerves from firing—seen as a negative if you are eating a pufferfish, but a positive to researchers working in a lab trying to understand the inner workings of nerves.

Recently, Stanford chemist Justin Du Bois, PhD, teamed up with radiologist Sandip Biswal, MD, who studies the origins of pain, to see if this group of chemicals could be used to better understand (and maybe one day treat) pain. I wrote a story about the work and described Biswal’s frustration diagnosing the source of pain:

Biswal, an associate professor of radiology at the Stanford University Medical Center, spent a lot of time imaging parts of the body where people said they felt pain, trying to find the source. It was a frustrating task because often the source of pain isn’t obvious, and sometimes the source is far removed from where a person feels the sensation of pain. Other times, he’d see something that looked painful, surgeons would fix it, and the patient would still be in pain.

Along with some other collaborators, Du Bois and Biswal figured out a way to manipulate the toxins Du Bois had been studying so that they would latch onto nerves that send pain signals and be visible outside the body. When they tested the chemical in rats, they were able to see the location of pain in a living animal.

As with so much cool research, the team got its start with a seed grant from Stanford’s Bio-X. They recently started a company to see if they could develop their work into a useful drug or imaging technique.

Previously: Stanford researchers address the complexities of chronic pain, Exploring the mystery of pain, More progress in the quest for a “painometer”, Ask Stanford Med: Neuroscientist responds to questions on pain and love’s analgesic effects
Photo by Jason Mintzer Shutterstock

Orthopedics, Pain, Parenting, Pediatrics

On being a parent with chronic pain

Mom3The Atlantic posted a moving piece today written by a mother whose severe scoliosis has left her body in a near-constant state of pain. The author, Rachel Rabkin Peachman, points to a recent review of scientific literature documenting how children of parents with chronic pain are affected by their mothers’ and fathers’ condition:

The results, published in the Journal of Child and Adolescent Psychiatric Nursing, are, well, painful to read. It turns out that children whose parents experience chronic pain are at increased risk for adjustment problems and behavioral issues, and are more likely to complain of pain themselves. The whole family suffers.

Peachman details some of the studies’ findings. She also describes her own history with pain and parenting, and discusses the times she was unable to pick up and soothe her crying daughter. She writes:

Science may say the odds are against parents with chronic pain. And I know there are days I’m sidelined and short-tempered. But I’m determined to raise children who feel supported, secure, and loved. I don’t know what my future holds—surgery, therapies, or a lifetime of pain. But I have to believe that despite a deteriorating body, it’s possible to be a successful mother.

The entire piece is worth a read.

Previously: Image of the Week: The agony of painStanford researchers address the complexities of chronic painLetting go of control during chronic illness or pain and Chronic illness in childhood: One patient’s story
Photo by Miki Yoshihito

Stanford Medicine Resources: