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Pain Management: Opioid Adherence in Cancer Patients

This week, Real World Health Care speaks with Salimah H. Meghani, PhD, MBE, RN, FAAN. Dr. Meghani is an associate professor and term chair in Palliative Care at the University of Pennsylvania School of Nursing. She is also associate director, NewCourtland Center for Transitions and Health. Her main research interest involves palliative care, specifically understanding and addressing sources of disparities in symptom management and outcomes among vulnerable patients.

We asked her about her study on analgesic adherence and health care utilization in outpatients with cancer pain, recently published in Patient Preference and Adherence. We also discussed the role of non-pharmacological approaches in treating cancer pain.

Opioid Adherence Patterns

Real World Health Care: Last year, you published an article: Patterns of analgesic adherence predict health care utilization among outpatients with cancer pain. Can you provide a brief summary of the article and talk about the study’s implications for cancer patients with pain management issues?

Salimah H. Meghani, University of Pennsylvania School of Nursing

Salimah Meghani: This is the first study to understand how opioid adherence patterns, over time among cancer patients, relate to health care utilization outcomes. We used objective measures of adherence (Medication Event Monitoring System – MEMS) and novel adaptive methods recently validated by the co-author, Dr. George Knafl from UNC-Chapel Hill. We found that inconsistent adherence patterns of analgesics over time was significantly associated with hospitalization over a 3-month observation period. The interaction of inconsistent adherence and strong opioids (WHO step 3 opioids) was one of the strongest predictors of health care use. It should be noted that this was a serendipitous finding. We did not plan to study adherence patterns and health care utilization. It therefore needs validation in hypothesis-driven study.

RWHC: Are you currently involved in any new research programs studying pain management in cancer patients? If yes, can you briefly describe?

SM: Yes, I am studying outcomes of opioid adherence and adherence patterns among cancer outpatients. This is an important topic as few recent U.S. based studies exist on the topic despite all the recent guideline contentions (e.g., CDC guidelines for managing chronic pain including chronic cancer pain and ASCO response) and national policy debates on opioids.

How Patients Manage Cancer Pain

RWHC: What do you think are the biggest challenges facing researchers studying pain management in cancer patients? How can those challenges be addressed?

SM: One of the biggest challenges is that we know very little about how patients manage their cancer pain. We know that opioids are widely prescribed, but we also know that there is poor adherence to prescribed opioids. Other treatments such as acupuncture are not consistently covered by health insurance or lack data on clinical effectiveness. There is a need to understand how patients are managing their cancer pain and what health care systems can do better to address the great burden on unrelieved cancer pain. Future work should also include improving access to effective non-opioid treatments for cancer patients. My previous research has also documented racial and ethnic disparities in cancer pain treatment for African Americans, which requires continued attention.

Safe Opioid Use

RWHC: What do you think are the biggest challenges facing clinicians treating pain in cancer patients? How can those challenges be addressed?

SM: There is a lot of confusion among clinicians about the role of opioids and the safe and rational use of opioids among cancer patients. Unfortunately, there is little empirical evidence base about the outcomes of opioid treatment among cancer patients. A look at the recent CDC guidelines on managing chronic pain would indicate that cancer patients frequently, if not invariably, have been excluded from the studies of the outcomes of chronic opioid therapy. More empirical evidence is needed to help clinicians develop comfort in opioid prescriptions.

Non-Opioid Treatments

RWHC: What do you think is the role of non-pharmaceutical pain management therapies for cancer patients? How can clinicians integrate both pharmaceutical and non-pharma therapies for cancer patients?

SM: I think access to non-pharmacological treatments is the biggest problem. While the NCCN guidelines for cancer pain identify a number of non-pharmacological modalities, they are not readily accessible to cancer patients. I have argued this in a recent letter to JAMA Oncology about the CDC opioid guideline that recommends that non-opioid treatments should be the first line therapy for chronic pain. This paradigm assumes easy and consistent access to non-opioid treatments. Also, access to effective non-pharmacological treatments are very different among poor, minorities, those with limited literacy.

Global Disparities

RWHC: What initially attracted you to this field? What continues to inspire you about it?

SM: My original research interest was global disparities in opioid availability for cancer pain management and the role of the International Narcotics Control Board. After migrating to the United States, I became familiar with racial and ethnic disparities in pain care and the toll it has for patients and families. This work continues to inspire me.

A Big Pain

Editor’s Note: This article in our pain management series originally appeared in Biotech Primer Weekly. For more of the science behind the headlines, please subscribe.

The Science Behind Opiods

Emily Burke, BiotechPrimer.com

The opioid addiction epidemic gained attention at the highest levels of U.S. policy circles this past year, as presidential candidates that disagreed on nearly everything else vowed to make fighting the problem a priority if elected. In July, the U.S. Senate overwhelmingly approved a bill to strengthen prevention, treatment, and recovery efforts. And no wonder – according to the Center for Disease Control, opioid overdose deaths are at an all-time high – a stark reality that highlights the dark side of a class of treatments serving a vital need. Opioid pain medications manage the severe short-term or chronic pain of millions of Americans. While these medications mitigate needless suffering, joining forces are the government, corporations, and medical community to battle against opioid abuse and addiction.

We wonder: what is the science behind the headlines? So, let’s talk about how pain medications work, the different types on the market, and the approaches to developing less addictive versions of opioid drugs.

Opiods vs. NSAIDS

There are two main categories of pain medications, opioids and non-steroidal anti-inflammatory drugs (NSAIDs). Although these two categories of drugs work differently, they do share one thing in common: both are derivatives of natural products. The NSAID Aspirin is a synthetic version of an extract from willow tree bark, and opioids are synthetic versions of opium and morphine, which come from poppy flowers.

Aspirin works by inhibiting an enzyme called cyclooxyrgenase 1 (COX-1). Once stopped, COX-1 is no longer able to produce signaling molecules, called prostaglandins and thromboxanes. Prostaglandins and thromboxanes have a wide variety of functions, including mediating aspects of inflammation (fever and swelling) as well as promoting neuronal response to pain. Other NSAIDs, such as ibuprofen and naproxen, also work by inhibiting COX-1 or its sister enzyme COX-2.

Opioid pain medications, such as Oxycontin and Percocet, work by binding to mu receptor proteins on the surface of cells in the central nervous system (CNS) —think brain and spinal cord. While the CNS is tasked with relaying pain signals, opioids decrease the excitability of nerve cells delivering the message, resulting in pain relief—along with a feeling of euphoria in some users. 

Lessening the Pain

Short term medical used of opioid pain killers rarely leads to addiction—when properly managed. Due to the euphoria-inducing effects of the drugs, long-term regular use, or use in the absence of pain, may lead to physical dependence and addiction. And because regular use increases drug tolerance, higher doses are required to achieve the same effect, leading abusers to consume pain pills in unsafe ways such as crushing and snorting or injecting the pills. According to the Centers for Disease Control, 44 Americans die every day due to prescription painkiller overdose. At the same time, chronic pain is also a serious problem, affecting approximately 100 million U.S. adults, while millions of others suffer acute pain due to injury or surgery. The medical need for these drugs is very real despite the dark side.

The answer to developing less addictive drugs may be found in a drug that blocks pain without inducing euphoria. These new drugs will need a different mechanism of action than traditional opioid drugs, which bind to the mu receptors of cells inside the CNS. Drugs under development include those that bind to a different type of opioid receptor, the kappa opioid receptor. These receptors are present on sensory nerves outside of the CNS.

Preclinical studies suggest that targeting these receptors could be effective at reducing pain without driving addictive behaviors. A lead candidate, CR845, is currently in Phase 3 clinical testing for post-operative pain and pruritus (severe itching), and in Phase 2 clinical testing for chronic pain. Also under development are compounds that selectively activate cannabinoid (CB) receptors outside of the CNS. CB receptors inside the CNS are linked to the psychoactive qualities of marijuana; those outside the brain are found on white blood cells and have been shown to be involved in decreasing pain and inflammation. A lead CB receptor activator, CR701, is in preclinical development.

Also under development are small molecule inhibitors of ion channels – proteins on the surface of nerve cells that help to transmit pain signals by allowing positively charged calcium ions to enter the nerve. This plays a critical role in sending the pain signal to the brain, yet because it works on nerves outside of the brain, it has less of a potential for addiction.  Phase 1 clinical studies are currently underway of HX-100 for the treatment of painful diabetic neuropathy.

Another development is a derivative of capsaicin, a naturally-occurring compound found in chili peppers. Capsaicin has pain relieving properties and has been used as a natural remedy. The lead candidate, CNTX-4975, is a highly potent, synthetic form of capsaicin designed to be administered via injection into the site of pain. CNTX-4975 targets the capsaicin receptor, an ion channel protein on the surface of nerve cells. When CNTX-4975 binds the capsaicin receptor, the influx of calcium ions results in desensitization of the nerves, making them unresponsive to other pain signals. This effect can last for months, and only affects nerves near the site of injection. CNTX-4975 is currently in Phase 2b clinical studies for knee osteoarthritis, and Phase 2 clinical studies for Morton’s neuroma, a sharp pain in the foot and toe caused from a thickening of the tissue around one of the nerves leading to the toes.

Earlier this year, researchers at Tulane University published a paper that shows great promise for the development of effective yet non-addictive pain medications. They have developed a compound that is derived from the endogenous opioid endomorphin. Endogenous opioids are chemicals produced naturally by the body that bind to and activate the mu opioid receptors, resulting in pain relief and mild euphoria without the detrimental side effects associated with opioid drugs such depressed respiration, motor impairment, and addiction. Scientist have tried before to develop safer pain medications based on endogenous opioids, but have not been successful, due to the instability of these molecules. The Tulane team created a derivative of endomorphin that is stable and binds to the mu receptor in such a way that pain relief occurs, but not the negative side effects listed above. Clinical testing is expected to begin by the end of 2017.

An Antidote to an Overdose

Overdosing can be fatal since respiratory failure occurs at high blood concentration levels of opioids. If an overdose is suspected, the individual should be treated as quickly as possible with naloxone—a “competitive antagonist” of the mu opioid receptor. Simply put, a competitive antagonist binds the receptor without activating it. Since naloxone doesn’t activate the receptor, it doesn’t have any pain-relieving or euphoria-inducing qualities; rather, it prevents the opioid drugs from binding. It may also displace opioids that have already bound the mu receptor, aiding in the stoppage of an overdose.

Cocktail Fodder: Runner’s High

Some folks love to run; others avoid it at all costs. This might be explained by inherent differences in sensitivity to the natural opioids called endorphins that are released during exercise. Not everyone experiences the “runner’s high” — feelings of calm and mild euphoria – just like not everyone experiences euphoric feelings from pain medications. These differences may help to explain why some people enjoy exercise and others don’t, and why some people get addicted to opioids—while others can take them or leave them.

 

New Real World Health Care Series to Focus on Pain Management

I remember visiting my grandmother in the hospital in late 1989.  She was in the final stages of pancreatic cancer; her hospitalization was primarily meant to keep her comfortable until her passing.  She had a “button” that added morphine into her IV line.  Although the machine was programmed to deliver only so much morphine within a certain timeframe, she could push that button whenever she needed pain relief.  She never stopped pushing that button.

Krista Zodet, President, HealthWell Foundation

Over twenty-seven years later, the pain associated with and caused by cancer is still a challenge.  In fact, pain seems to accompany many of the diseases we help with at HealthWell and we certainly hear so from our patients.  Even in life outside of HealthWell, I hear from friends and family members stricken with chronic pain related to surgery or an injury and their struggles to manage it productively.

Their stories are powerful and many put into words a pain that I cannot fathom trying to cope with day in and day out.  From minor headaches and injuries, to the effects of major surgeries and chronic disease, pain is an unfortunate fact of life for millions of Americans. It affects more Americans than diabetes, heart disease and cancer combined, according to the American Academy of Pain Medicine.

In a 2011 report, the Institute of Medicine estimated that 100 million adult Americans experience chronic pain every year, costing the nation between $560 billion and $635 billion annually. Much of this pain is preventable or could be better managed, according to the committee that wrote the report, which called on health care providers, insurers and the public to have a greater understanding about pain: Although pain is universal, it is experienced uniquely by each person and care often requires a combination of therapies and coping techniques. It is more than a physical symptom and is not always resolved by curing the underlying condition.

We at the HealthWell Foundation agree with the authors of the IOM report in believing that successful treatment, management and prevention of pain requires an integrated approach that responds to all the factors that influence pain.

We also share the growing concern about the role of opioids in treating pain. In its Guideline for Prescribing Opioids for Chronic Pain, the CDC notes that opioid pain medication use presents serious risks, including overdose and opioid use disorder. CDC estimate that nearly 2 million Americans age 12 or older either abused or were dependent on prescription opioids in 2014.

Over the next couple of months, we will be focusing on the issue of pain management, including traditional pharmaceutical approaches and non-traditional alternative therapies. We’ll be interviewing top researchers in the field as well as leaders of clinical organizations dedicated to helping patients manage pain.

We invite you to check back to learn more about what’s working in the field of pain control and the challenges researchers and clinicians continue to face, especially in light of the growing issue of opioid addiction. You can also sign up to receive email alerts when new interviews are posted. Just enter your email address under the sign-up message to the right.

Nine Ways You Can Reduce the Pain and Fear of Needing a Needle

This is the second installment in a two-part series on what’s working to prevent and address needle fear. To learn more about needle phobia and what health care providers are doing, check out Part I: “A Shot of Courage for Those Who Fear Needles”. Click to view Amy Baxter’s TED talk on Pain, Empathy, and Public Health.

“Fear is the mindkiller. Fear is the little death.” – Frank Herbert, Dune

Amy-Baxter

Amy Baxter

In 1995, a scientific paper was published for the first time evaluating the prevalence of needle fear and its effect on accessing health care. Since then, studies suggest that the fear of needles is rising, afflicting a quarter of adults and two out of three children.

Needle phobia seems to be more likely in people who are sensitive to a light touch and sharp objects, particularly those with the “red head pain” MC1R gene. While most people acquire needle phobia around age four to six, about three to five percent of people have a genetic predisposition to become lightheaded or nauseated or even to faint.

But whether acquired or innate, fear not! Quite literally – here are nine ways to reduce the pain and fear of needing a needle at any age.

1. Pain Management.  When time permits, needle pain can be greatly reduced by using topical pain relief – specifically, topical anesthetic numbing creams and gels — which numb the skin in 20-60 minutes. Fun tip: use Glad® Press-N-Seal rather than the commercial medical covers. It is more comfortable to remove and much less expensive.

2. Let your brain do its thing.  Overwhelm other competing nerves with sensations that aren’t so painful. Studies have found that when someone’s hand is in ice water, they can handle more intense pain everywhere else in the body. This works both through something called gate control (e.g. cool water soothes a burn) as much as brain bandwidth. Vibration and cold have been studied together; when put between the brain and the pain (especially after numbing a shot area directly), they can decrease needle pain up to 80%.

3. Relax the muscles.  Pushing medication into taut muscles makes it hurt more, now and later. Even passively stretched muscles hurt. Rather than bending over and going for a gluteal stick, try lying on your side with the buttocks muscles relaxed. Do the same for thigh shots; sitting up causes the muscles to be active keeping you balanced, so go for a side position.

4. Distract your mind.  Counting and engaging in unrelated tasks can reduce pain by half. At a minimum, count corners, ceiling tiles, or holes in an air grate. Some studies have found that active engagement can be more effective at reducing pain for teens and adults. Drawing on an iPad game or finding items in “I Spy” apps, can work at any age.

5. Distract your senses.  The brain can only process so much at one time. Buy five packs of sugar-free gum, mix the sticks, pick one at random, and try to figure out the flavor. Drink a slug of a cold, sweet beverage. Taste and smell are great senses to counter paying attention to pain.

6. Focus on something you can control.  Whether you’re thinking about the health or life benefits of the shot, concentrate on that. Fertility shots, for example, can have an adorable payoff. Building an idea in your mind and mentally “going there” can help with pain.

7. Create a different sensation.  Pinching your own finger and focusing on that or forcing a cough have both been shown to decrease needle pain. Squeezing your toes, stretching your calf, or making any distant body part more noticeable to your brain will take attention away from the area of pain.

8. Be a scientist.  If you know you have multiple needle events coming up, keep records of what works best and what doesn’t. Being an observer, even of yourself, adds distance that can give you more control. More control = less fear. Less fear = less pain.

9. Speak up!  Let your care team know you don’t like needles, and let them know what you have found what works for you. “You know how some people pass out with needles? Shots and I don’t get along, so let me tell you what works for me. I really appreciate you listening to me; it makes everything go so much better for both of us. What seems to help me is this: “____.” Even if you haven’t ever gotten lightheaded or passed out, reminding care providers of people who have can help establish that you understand that procedural pain is important and you give them credit for appreciating it, too.

Do needles make you nervous? Have you found a strategy that reduces needle anxiety or pain? Post your experiences and tips to the comments section.

You can reach Dr. Amy Baxter at abaxter@mmjlabs.com.

Should clinicians replace medication with an ancient spiritual practice?

Researchers from Johns Hopkins University sifted through over 18,000 studies on a potential treatment for pain, anxiety and depression, narrowing their meta-analysis to 47 scientifically rigorous clinical trials. The results, published in the journal JAMA Internal Medicine, revealed what many have experienced over thousands of years: while it’s not a cure-all, this treatment can help alleviate pain, anxiety and depression. The treatment? Meditation.

David Sheon

David Sheon

Meditation began as an ancient spiritual practice but is now also utilized outside of traditional settings to promote health and well-being. The study findings incorporate the effects of mindfulness meditation on over 3,500 participants who were selected to take part in either a meditation regimen or a different therapy, such as exercise. Overall, researchers found that the effect of meditation on participants was moderate and on par with that of prescription medications.

While this is a promising result on the benefits of meditation, the researchers identified a number of limitations. The study did not find any evidence of meditation affecting other health concerns such as positive mood, attention, substance use, eating habits, sleep and weight. Also, meditation did not provide any long-term therapy as compared to medication. “The benefits did attenuate over time — with the effectiveness of meditation decreasing by half, three to six months after the training classes ended,” said study leader Dr. Madhav Goyal, an assistant professor of medicine at Hopkins. “We don’t know why this occurred, but it could have been that they were practicing meditation less often.”

Still, Dr. Goyal said he is encouraged by the study’s results, specifically because of the short training periods for the participants. There may be greater potential for individuals with more instruction or experience in meditation. “Compared to other skills that we train in, the amount of training received by the participants in the trials was relatively brief,” he said. “Yet, we are seeing a small but consistent benefit for symptoms of anxiety, depression and pain. So you wonder whether we might see larger effects with more training, practice and skill.”

While the new study suggests that in some cases, meditation may be used in addition to or in lieu of prescription drugs to treat pain, anxiety and depression, it is important for patients to consult their doctors before altering any course of treatment.

At RealWorldHealthCare.org, we have been interested in meditation’s potentially positive impact on health. Last April, we posted about a recent study in which meditation halved the risk of death, heart attack and stroke in African American men.

Meditation may have economic benefits as well. According to a July 2013 Huffington Post blog, Aetna’s employee health care costs went down by 7 percent in 2012 after the company implemented a wellness program, which CEO Mark Bertolini attributes to reducing stress through meditation and yoga. In recognition of its positive health impact, some insurance companies provide benefits for meditation instruction. For example, CareFirst’s Options Discount Program offers up to 30% off fees for participating meditation instructors. In 2010, Americans spent more than $11 billion on antidepressants, according to the American Psychological Association.

The National Center for Complementary and Alternative Medicine of the NIH offers an introduction to meditation, its uses and guidance for those who wish to practice meditating. The National Meditation Specialist Certification Board, an organization that seeks to promote meditation as a specialized field in health care, keeps a directory of meditation specialists, and there are many other such directories available online or through participating insurance providers.

In a Psychology Today article guiding those interested in mindfulness meditation, Dr. Karen Kissel Wegela emphasizes that sick or healthy, meditation can help people cope. “The sitting practice of mindfulness meditation gives us exactly this opportunity to become more present with ourselves just as we are,” she says. “This, in turn, shows us glimpses of our inherent wisdom and teaches us how to stop perpetuating the unnecessary suffering that results from trying to escape the discomfort, and even pain, we inevitably experience as a consequence of simply being alive.”

Have you ever meditated? Have you or someone you know ever meditated to treat depression, pain or anxiety? Did you find it effective?

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