Posted tagged ‘opioids’

Pain catastrophizing linked to opioid use, particularly for women, Stanford study shows

June 15, 2017

Photo by ZeeNBee

Our nation is struggling with an unprecedented opioid epidemic, which is pushing researchers to better understand how people experience pain and how this is impacts pain treatments.

A key factor may be something called pain catastrophizing — heightened negative thoughts and emotions in response to actual or anticipated pain. New research recently published in Anesthesiology shows that pain catastrophizing is a risk factor for prescription opioid misuse, and the role it plays is different for men and women. I connected with Beth Darnall, PhD, a Stanford clinical associate professor of anesthesiology, perioperative and pain medicine, to learn more about her new study, whose first author is Yasamin Sharifzadeh-Moghaddam, a medical student at Virginia Commonwealth University.

What is pain catastrophizing?

“Pain catastrophizing is the rumination and magnification of pain, and feelings of helplessness about it. People who catastrophize have a hard time thinking of anything but their pain. It’s common for people with chronic pain to catastrophize to some degree, but when it gets into the clinical ranges it indicates a need for treatment. Treatment involves learning targeted ways to redirect one’s attention, calm the nervous system in the face of pain and stress and cultivate awareness about what one can do to feel better. I think virtually everyone with chronic pain can benefit from learning skills that empower them to have better control over their pain and distress — even those who are not high catastrophizers.”

What inspired you to research pain?

“First, I was intensely curious about pain and why it varies between individuals; a lot of the “why” ends up involving psychological factors. I was fascinated with the connection between stress and pain and wanted to learn more about how they relate. … I also wanted to help people on a broader scale. I can only see a few individual patients in the clinic, but if I develop a treatment that others can use, the ripple effect potential is tremendous.”

How did you investigate the impact of pain catastrophizing on opioid use?

“Pain catastrophizing is associated with greater use of opioids after surgery and with opioid misuse. Across multiple studies, catastrophizing associates strongly with pain intensity, so we wanted to better understand how it might relate to pain medication.

In our study, we looked at patients receiving a new evaluation at the Stanford Pain Management Center. We examined the relationships between pain intensity, pain catastrophizing and existing opioid prescription. We used the Collaborative Health Outcomes Information Registry, a free open source health outcomes platform, to collect data on almost 1800 patients. We aimed to reveal whether sex differences existed for opioid prescription and our other variables of interest, using modeling to explore the associations. We found that almost 60 percent of patients referred to our center are taking prescription opioids, and people with greater pain were more likely to be taking opioids.

We also found that sex matters in the equation. For women, the relationship between pain catastrophizing and opioids occurred at much lower levels of pain catastrophizing than for men. Our data suggest that catastrophizing may be more impactful for women, and that these associations begin to appear at what we previously called ‘subthreshold’ levels. More research is needed to replicate our findings and to understand why we see these sex differences in catastrophizing and opioid prescription. I’m speculating, but women may be better communicators of pain-related distress — verbally and nonverbally — and this may translate into a prescription at the end of a medical visit.”

How can your results improve future clinical practice?

“If replicated, our findings signal that we should be treating our patients before frank problems arise. If we address psychosocial distress early on, we may prevent worsening of symptoms into clinical problems and the need for various treatments. We also need more research to develop a deeper understanding of the relationships between prescription opioids and psychological factors. … Our findings suggest that we need to further examine the prescribing doctor-patient interaction.”

What’s the next step?

“We are currently examining whether presurgical treatment for catastrophizing can reduce post-operative opioid use. Right now we are studying this in women only, but our planned studies include men and women so we can test sex differences in treatment response.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Opioid receptors in brain affect reaction to another person’s pain

June 7, 2017

Image by P. Simonau

Watching someone else suffering from pain is distressing. What mechanisms cause that distress? And why do some of us experience it more strongly than others?

A new Finnish research study has now demonstrated that seeing others in pain activates the same brain regions involved in firsthand pain, which suggests that a shared neuromolecular pathway processes both types of pain. Specifically, the researchers showed that the endogenous opioid system, but not the dopamine system, contribute to vicarious pain.

The endogenous opioid system is a set of neurons in the brain that naturally produces opioids to help modulate emotions and pain. Similarly, the dopamine system consists of neurons that synthesize and release dopamine, which helps manage motor control, pain, reward and addictive behaviors. So both of these systems are known to play an important role in processing firsthand pain, but their role in vicarious pain was unexplored.

The research team conducted the study by imaging 35 healthy women ranging in age from 19 to 58 years old. First, they performed two positron emission tomography (PET) studies on different days using radiopharmaceuticals that quantified the availability of opioid and dopamine receptors in each woman’s brain to better understand the individual opioid and dopamine systems. Next, they investigated how each woman responded to vicarious pain by performing a functional MRI scan while she watched videos of humans experiencing painful and painless situations.

The researchers found a negative correlation between opioid receptor availability and response to vicarious pain — women with less opioid receptors reacted more strongly to seeing someone else’s distress, as recently reported in Cerebral Cortex. In contrast, they found no correlation with the dopamine receptor availability.

The authors concluded in the paper, “These results suggest that the opioid system contributes to neural processing of vicarious pain, and that interindividual differences in opioidergic system could explain why some individuals react more strongly than others to seeing pain.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Engineering better opioids: A podcast featuring Stanford bioengineer Christina Smolke

May 31, 2017

Obtaining compounds from nature, such as opioids from poppies or taxol from yew trees, is hard and time-consuming. So researchers, including Stanford’s Christina Smolke, PhD, are working to synthesize medically useful compounds by reengineering nature.

Smolke, a professor of bioengineering, describes her efforts to engineer yeast to make opioids on a recent episode of the “Future of Everything” radio show.

“These are compounds in nature that the opioid poppy has evolved to make. And to date, our chemists have not been able to develop efficient processes to make these compounds,” Smolke told show host Russ Altman, MD, PhD, a professor of bioengineering, of genetics, of medicine and of biomedical data science. “So we still farm this drug crop of opioid poppy to produce these molecules and the raw materials to make these molecules. And there are many limitations that come about from doing that.” These limitations include environmental and geopolitical risks, she said.

Smolke explained that she tackled this research even though many experts in the field viewed it as impossible — because it involved reengineering a complicated set of reactions and mix of enzymes that work together within the opioid poppy to build the opioid molecules. Over 10 years, her research team developed the very challenging platform technology to “prove that it could be used with any compound found in nature.”

“The final yeast strain that made the initial opioids molecules had 23 different enzymes put into it. So one of the challenges was identifying the enzymes from the opioid poppy and then moving them into yeast,” Smolke said.

But the trickiest part, she explained, was getting them to work in yeast, which is a very different organism than opioid poppies. The researchers had to modify each of the enzymes to create a yeast strain that could churn out opioid molecules.

There is more work to do though, including creating yeast that are more efficient at making the opioid compounds, as well as using the technology to make better opioids with less side effects so they are less addictive. Luckily, Smolke expects her new research projects to go more quickly now that they’ve developed the basic tools.

“We’re probably around 5 years away from molecules coming from yeast-based platforms to actually be in the medications that you’re taking,” Smolke explained. “Some of that lag is due to the engineering that we have to do to make the processes efficient enough so they can be scaled up at a commercial setting. And others are [due to] regulatory approvals.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

On addiction, psychiatric disorders and primary care: A Q&A with a Stanford clinical psychologist

April 6, 2017

Photo by Eric Norris

Resolving America’s opioid crisis is clearly more difficult than just saying “no” to opioid use.

A key complication is that many opioid addicts also have mental health issues, said Mark McGovern, PhD, a professor of psychiatry and behavior sciences who joined Stanford in January. McGovern’s research focuses on patients with both psychiatric and addiction disorders. I connected with him via email.

What inspired you to focus on patients with both psychiatric and substance use disorders?

“In my personal experience and clinical practice, it seemed obvious that many people who had a problem with alcohol or drugs also had a mental health issue, whether it was depression, anxiety or something else. When I entered the world of research, the epidemiological and clinical prevalence data verified my anecdotal experience. About 70 percent of patients with a diagnosis of a drug or alcohol disorder have another psychiatric disorder. And of those with a psychiatric disorder, approximately 50 percent have had a substance use problem at some point. Ironically, our mental health care system, including our education and training programs, are organized as if people have one or the other problem but not both. It turns out that if a person has both types of disorders, their life outcomes are significantly worse. This struck me as an enormous health-care disparity.”

How do you treat these patients?

“I spent the past 20 years designing interventions that address these ‘co-occurring disorders’ within the same treatment course. We worked with systems of care — including large organizations, counties, states, tribes and nations — to reconfigure services to provide integrated care. These efforts included the use of both psychotropic and addiction medications, integrated combined therapies, and changes in attitude, philosophy, organizational structure and financing.

We need to address these behavioral health issues in both primary care and specialty settings.

Common problems such as depression, anxiety, alcohol and drug use disorders are ubiquitous in primary care settings. As with any medical condition, early intervention before disease progression results in better outcomes. Further, most people with these conditions don’t seek specialty care, but typically do see their doctor for other problems or routine health-care visits. Unfortunately, substance use disorders typically aren’t screened for in primary care, and they are currently addressed in only the most obvious and severe cases. People at Stanford are just beginning to develop an innovative ‘unified model of behavioral health integration’ that fully addresses the complex array of behavioral health conditions.”

How do you use addiction medications?

“Before I arrived at Stanford, I was at Dartmouth where I consulted with the states of northern New England — Vermont, New Hampshire and Maine — to combat the opioid addiction epidemic, including heroin and prescription narcotics. There are three FDA-approved medications for opioid addiction: methadone, buprenorphine and naltrexone. Unfortunately, even though they are very effective, these medicines are not widely available to people with opioid addiction. We worked most closely with physician practice groups across Vermont to prescribe buprenorphine and naltrexone and deliver high quality care. For example, we used learning collaboratives to engage physicians, improve access to buprenorphine and reduce the variability between different doctors. Overdose death rates in all New England states except Vermont have continued to rise, whereas Vermont’s has decreased since 2015. And the number of Vermonters receiving addiction medications has grown from 800 in 2013 to close to 5000 today.

I remember meeting my patient Bobby (a pseudonym) who was a general contractor with a successful business. He injured his back in 2004 and was prescribed Percocet for pain by his primary care physician. Gradually, he noticed that he needed more medication to get the same pain relief, emotional relief and stress reduction. Over time, Bobby shuffled from doctor to doctor to obtain opioid prescriptions allegedly for his family members. He transitioned to heroin by 2006. Prior to his opioid addiction, Bobby had no history of illegal activities and no substance problem. Bobby’s wife did some online research and learned about addiction medications. They were both drawn to the possibility of buprenorphine because he might be able to get it from a ‘regular doctor’ without going to rehab and ruining his business. Bobby was seen in our clinic and responded extremely well to the medication, and discontinued his use of other opioids. Interestingly, he said that he still had occasional pain but it was more important to be ‘functional than pain free.’”

What advice do you give to trainees?

“When educating medical students, psychiatric residents and fellows and clinical psychology interns at Stanford, I advise them to:

  • Understand addiction as a chronic medical condition that has its basis in the brain, even though its manifestations radiate across the person’s life, relationships and world.
  • Empathize with the person who is suffering with this condition, who may not be able to accept or describe it clearly, but who is nonetheless struggling to control It’s not their choice; it is not their ‘Plan A’ in life.
  • Know that effective treatments are available, and that you can provide them.
  • Have high hopes that recovery is possible for patients with addiction.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Targeting protein may help researchers improve pain medication

January 24, 2017

headache-1910649_1280For many people, living with chronic pain is a way of life. Unfortunately, existing pain medications are not always effective and can be addictive, which has led to an opioid epidemic in the United States.

In their search for better therapies to manage pain, researchers are investigating the underlying mechanisms that signal and control pain in the body. A central component of this pain pathway is a protein called Nav1.7, which is present at the endings of pain-sensing nerves. Nav1.7 is known to help alert your brain when your body encounters potentially harmful stimuli, like when your hand touches a hot pan.

Past research demonstrated that people with non-functioning Nav1.7 don’t feel pain. This discovery led to the development of drugs that block Nav1.7 activity. Unfortunately, these drugs didn’t really work. It turns out that the role of Nav1.7 is more complicated than first thought.

“It seemed so obvious and simple, but it was not so simple,” said Tim Hucho, PhD, a neuroscientist at the University Hospital Cologne in Germany, in a recent Science News story.

Researchers have now found that Nav1.7 plays a second role — triggering the production and release of natural opioid compounds, like endorphins, that suppress the transmission of pain signals to the brain. People with non-functioning Nav1.7 do not feel pain and have increased expression of the genes in charge of making natural opioids.

The news story explains:

“An investigation of rat and mice nerve cells reveals the tug-of-war between Nav1.7’s pain-promoting and pain-relieving powers. Cells with nonfunctioning Nav1.7 have amped up activity in the cellular machinery that kicks off pain relief, Hucho and colleagues report. They suggest that Nav1.7 acts like the axis point in a playground seesaw. When the pain-promoting side is dialed down, the pain-relieving side becomes more dialed up than usual, and cells make more of their in-house opioids.”

This research suggests a new approach to pain management: using opiates in combination with a Nav1.7 blocker to make opiates more effective and reduce their associated side effects. However, a lot more research is needed before this work can be translated into treating people with chronic pain.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

The Opioid Crisis: Medicine X panelists explore the complexity of managing chronic pain

September 19, 2016
britt-johnson-on-stage-1024x683

Photograph courtesy of Medicine X

Saturday’s Medicine X session on the opioid crisis focused on how best to manage the chronic pain felt by millions of Americans every day. The session engaged panelists with different perspectives, including a patient in chronic pain and physicians struggling to decide when to prescribe opioids. All the panelists recognized that opioid addiction is a serious and pervasive problem, but they also warned that proper pain management is a complex issue.

Jeanmarie Perrone, MD, professor of emergency medicine at the Hospital of University of Pennsylvania, told the audience, “I need good pain management to work in the emergency room. We need these drugs, we just need to be conscientious about it.”

ePatient Britt Johnson, a Medicine X board member and owner of The Hurt Blogger, understands this all too well. She shared her story of needing opioids to function due to severe pain from spondyloarthropathy and rheumatoid arthritis, which she’s had for most of her life.

Johnson addressed the media’s oversimplification of the issue. “Pain is not politically correct,” she said. “The media tells me that all opioids are all bad. The media makes everyone believe that I, too, am struggling with addiction. And the media lumps me in with statistics on heroin usage and overdose deaths.” She went on to say that she winds up “feeling guilt and shame for constantly experiencing pain. And I’m reminded constantly how heart breaking overdose stories are, which they are. But my story is not connected to those stories.”

Pain expert Frank Lee, MD, agreed that “we’re starting to stereotype chronic opioid patients as heroin addicts and physicians as pill pushers.” Lee described the impact of this on his practice and how it increases his risk if he prescribes a large or moderate dose of opioids to a patient. “If I just follow the CDC guidelines and tell the patient that I can’t prescribe this medication, it makes my life easier,” he said.

Lee shared a story about one of his patients who recently died. In her 70s, Mary had severe rheumatoid arthritis and three back surgeries. When he “inherited” Mary from a different pain doctor, she was on massive doses of opioids — close to 300 mg morphine daily equivalents, several times the recommended dose. “Maybe I was naïve, but I went through all the dangers of opioids. I told her, ‘We need to come down on your dose.’ She was hesitant, but she said ‘if you really need to do this, okay.’ During the next three months, we went down from almost 300 mg to about 70 mg. She ended up in the emergency room twice, because she just couldn’t take it. It hurt too much,” he said. “She cared enough to try what I recommended and I felt like I owed her the chance. We went back to the insane amount of her opioids and she did well.” However, Lee expressed his concern over what the high opioid doses did to her body.

Lee and others discussed the need to distinguish between patients like Johnson and Mary from those who are prone to opioid addiction. Sean Mackey, MD, PhD, chief of the division of pain medicine at Stanford, declared the need for more quality data on pain — through programs like the National Pain Strategy — to help identify the risk factors of the people that are more vulnerable. Cynthia Reilly, director of the prescription drug abuse project at The Pew Charitable Trusts, professed that prescription drug monitoring programs are part of the solution.

The panel agreed that another solution is to make integrated medicine options more affordable. “At the pharmacy I get a bottle of 60 Percocet for ten dollars, yet I have to pay out of pocket for massage, acupuncture, heat therapy, ice packs, cognitive behavioral therapy, pain psychologists and anything else,” said Johnson. “Opioids have the cheapest barrier to access, yet raising the price of opioids is not the answer; putting complimentarily pain therapies on an even playing field is.”

Although mostly harmonious, the panel discussion became heated near the end when a member of the audience interrupted, asking to hear more from Johnson. Feeling that she was being left out of the conversation, she said, “I’m sitting here and the discussion about the pain crisis is happening around me, when I’m right here and it could be happening with me. We could be having a real discussion here.” The panel concluded that we need to do a better job bringing everyone together with different perspectives.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.


%d bloggers like this: