12
Opioids and the Treatment of Chronic Pain
Pain is a universal human experience. Treatments and remedies for pain abound in folk medicine and traditional systems of healing, many of them effective, especially for acute pain. Most effective of all is the opium poppy (Papaver somniferum), used in the Old World since ancient times. Derivatives of opium—from morphine and codeine to oxycodone (OxyContin)—collectively known as opioids, are still our most powerful analgesic drugs. They are quite safe when used appropriately, especially for short-term management of acute pain. But long-term use to treat chronic pain is another story. Overuse, misuse, and abuse of opioids are now rampant, harming individuals and society. According to figures from the Centers for Disease Control, in 2010 American physicians prescribed enough of them to treat every adult in the country around the clock for a month. In the political campaigns leading up to the 2016 presidential election, voters in many states, especially in New England, told candidates that opioid abuse was their greatest concern, more so than the economy or threats of terrorism.
Greg graduated high school with honors. Several years later, in 2007, he decided to join the army, as many members of his family had before him. During his initial fifteen-month tour in Iraq, which involved several combat missions, he wrote to his girlfriend and parents about his increasing battle with depression and frequent nightmares. Shortly after returning home he was diagnosed with post-traumatic stress disorder (PTSD) and received counseling for several months. After additional training, Greg returned to Iraq for a second tour in 2010, serving as a medic for his unit in Baghdad.
During his time in Iraq he was involved in four improvised explosive device (IED) attacks, suffering a painful shoulder injury as well as a concussion. (The concussion was caused by an explosion that killed several members of his unit in the Humvee in front of him.) Because his initial treatment with NSAIDs and physical therapy did not significantly reduce his pain, he began receiving daily opioids, including hydrocodone combined with acetaminophen (Vicodin). In addition to his shoulder pain and nearly daily headaches, Greg was dealing with severe anxiety, insomnia, and nightmares. He also experienced significant weight gain and had recently been diagnosed with pre-diabetes. Subsequent to his discharge and evaluation at the local Veterans Administration (VA) hospital, he was diagnosed with mild traumatic brain injury (TBI). During a series of medical visits with different providers, his pain medications were escalated to long-acting morphine, oxycodone combined with acetaminophen (Percocet) as needed, plus alprazolam (Xanax) and zolpidem (Ambien).
Greg had hoped to find work in health care, but he was unable to hold a steady job. At one point, after being fired, he told his girlfriend that he was “ready to end it.” She contacted his parents and siblings, who arranged to have him evaluated at a regional VA medical center with integrative medicine capabilities.
At his appointment, he discussed his feelings of failure and increasing thoughts of suicide. He also admitted to memory lapses and bouts of aggression that affected his relationships and ability to work. He confided that he was storing his opioid medication for the day that he could “no longer manage.”
At this point a comprehensive plan of care was developed. Initially he was placed on a monitored detoxification program with behavioral counseling, including cognitive behavioral therapy. In addition, his team provided cranial therapy, acupuncture, and healing touch for pain relief as well as nutritional and exercise therapy to manage his weight and blood sugar. He also attended classes during his treatment, including a yoga program, tai chi, and vocational rehabilitation. After more than three months of intensive behavioral and integrative care he was able to return home, off all pain medication. He now relies on daily home exercise and biofeedback to keep his pain and anxiety under control. He has also been able to secure a job with a local nonprofit agency that helps homeless veterans with basic health care needs and housing.
THE NATURE OF CHRONIC PAIN
Pain can persist in the absence of the event that triggered it, developing into a stubborn, debilitating syndrome of chronic pain that resists treatment, undermines quality of life, and causes great frustration for patients, doctors, families, and society. The incidence of chronic pain syndrome has increased enormously in recent years, becoming a costly burden on the health care system and provoking much debate about treatment strategies. One reason for the increase is the number of returning war veterans with devastating injuries, many of which would have been fatal were it not for recent advances in trauma medicine. Poor treatment outcomes in this group, along with dependence on opioids, have drawn more attention to the difficulty of managing chronic pain. An emerging consensus is that medication alone cannot solve the problem.
Pain is the most common reason people see a doctor worldwide. It may start as an acute bout of low back, neck, or head pain. In most cases these episodes resolve, but for more than 1.5 billion people worldwide and more than 100 million Americans, the problem lasts more than several months, becoming chronic. Not only does pain at the initial site worsen with this transition, it becomes more likely to gradually transform into an entity that requires a completely different approach from the one we currently use. Chronic pain syndrome is also associated with trauma, migraine, arthritis, fibromyalgia, and neuropathy (nerve pain, a common complication of diabetes and adverse effect of some forms of cancer chemotherapy).
We now understand that as pain becomes chronic, brain areas that perceive it begin to change physically and to communicate with nearby areas in the brain that normally have nothing to do with pain. Involvement of these other regions appears to be related to difficult symptoms that often accompany chronic pain, such as fatigue, disturbed sleep, depression, anxiety, and cognitive impairment. These “comorbidities” greatly complicate the management of chronic pain, making it fundamentally different from acute pain. In many settings, unfortunately, patients with chronic pain syndrome are still treated as if they have acute pain.
The newer, integrative approach stresses individualized treatment and uses many different modalities coordinated by a team of health care professionals. Analgesic medication is a component of this approach but never the sole component or even the most important one.
NSAIDS AND ACETAMINOPHEN
Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used analgesics, along with acetaminophen (Tylenol), also known as paracetamol, a different kind of medication that has little effect on inflammation. People commonly self-medicate with these drugs, and those with chronic pain syndrome may take them frequently over long periods of time.
NSAIDs are discussed in detail in chapter 8. They have significant potential for harm with long-term use as well as for interactions with other drugs, and they should never be stand-alone treatment for chronic pain.
Acetaminophen is comparable to aspirin in analgesic efficacy. It is generally safe, although overdoses, which are not uncommon, can cause severe liver damage and liver failure. In fact, acetaminophen toxicity accounts for most cases of acute liver failure in the United States and other Western countries; many of these are seen in emergency rooms, many require hospitalization, and some result in death. People who drink alcohol regularly are at greater risk of overdose, as are recreational users of products that combine acetaminophen and opioids; many such prescription medications are diverted to the black market. Heavy drinkers and those with known liver disease should be cautious about relying on acetaminophen to manage chronic pain.
OPIOIDS
For moderate to severe acute pain, opioids are the drugs of choice. Two natural constituents of opium—codeine and morphine—have been around for a long time.* Codeine is a weak analgesic, often combined with aspirin or acetaminophen, and also used as a cough suppressant. Morphine is a major analgesic medication; like other opioids it is much more potent when administered parenterally—that is, not by mouth but by injection into a muscle or vein. Over the years, chemists have tinkered with these molecules to produce dozens of semisynthetic and synthetic analogs, often in a vain attempt to separate the analgesic properties from the addictive ones. Heroin was released to the world in 1898 as a safe and effective cough suppressant and pain reliever with none of morphine’s risk for dependence, which by then was well known,* and there have been many similar claims made for new opioids ever since. Recently, pharmaceutical manufacturers have made available long-acting forms of morphine (like MS Contin) and other opioids, such as fentanyl (Duragesic), hydromorphone (Dilaudid), and oxycodone (OxyContin).
Opioid drugs work by activating the same brain receptors that bind opioids made within the body. These natural or endogenous opioids include endorphins, which affect mood and pain perception and can be released by many triggers, including exercise and acupuncture. It just happens that molecules made by the opium poppy bind to those same receptors.
For acute pain that resists NSAIDs and acetaminophen, opioids are very effective. They also work well for some types of chronic pain but not so well for others. Many experts now agree that the risks associated with use of these drugs are likely to outweigh the benefits when they are used long term for most types of non-cancer pain, including headache, back, and neck pain. For chronic pain that is episodic, such as pain associated with migraine, fibromyalgia, and neuropathy, acetaminophen and NSAIDs are preferable to opioids. A 2006 epidemiological study concluded, “It is remarkable that opioid treatment of long-term/chronic non-cancer pain does not seem to fulfill any of the key outcome opioid treatment goals: pain relief, improved quality of life, and improved functional capacity.”
THE PROBLEMS WITH OPIOIDS
Opioid overdose can cause fatal depression of respiration by direct action on the brain center that controls breathing. This is unlikely in patients taking them regularly for chronic pain, because tolerance to this effect develops rapidly. It is more likely when opioids are combined with sedative drugs. The combination of opioids and benzodiazepines (“benzos”—see chapter 9) is especially dangerous, quadrupling the risk of overdose. (Greg, in the case presented at the beginning of this chapter, was on several opioids and two benzos.)
Otherwise, the adverse effects of opioids are more sources of discomfort than threats to life. Most common are nausea and vomiting, itching, sweating, dizziness, drowsiness, and constipation. In the elderly, dizziness can increase the risk of falls. Constipation can be severe. Some people on long-term opioid treatment experience an odd intensification of sensitivity (hyperalgesia), making the lightest touch unbearable and the pain actually worse.
In end-of-life care—for example, of people with end-stage cancer who are experiencing constant pain—opioid analgesia may be a necessity, but the cognitive effects of the drugs, sometimes called “mental clouding,” can be distressing for those who wish to remain lucid through the dying process and be able to communicate with loved ones. Some hospice physicians say that managing pain with opioids in this setting is challenging, and that it takes skill and art to provide adequate analgesia without diminished awareness.
Of course, the overriding concern about long-term use of opioids is addiction and its destructive effects on individual lives and on society. Regular use of any opioid analgesic can lead to tolerance (the need for higher doses to maintain a desired effect), physical dependence, and addiction. Physical dependence, marked by prominent withdrawal symptoms when an opioid is discontinued, is common but is not the same as an addiction disorder, which is much more serious. An estimated 5 percent of those who stay on opioids for more than a year develop addiction disorder. People who experience euphoria from opioids, especially when they first receive them by injection, are more at risk, as are those who rely on opioids to dampen psychological pain. (As noted earlier, psychological distress is a major component of chronic pain syndrome.) Addiction disorder represents derangement of the brain’s reward system. It is characterized not only by physical dependence but by obsessive focus on the drug, behavior problems, impaired social functioning, and loss of productivity.
In the late 1980s and early 1990s, use of opioids increased dramatically. This followed a call by noted pain clinicians to not undertreat pain, including non-cancer-related pain. It was also spurred by the introduction of the long-acting forms mentioned above and their vigorous promotion by manufacturers. The US Food and Drug Administration found it necessary to issue warning letters to some of these manufacturers. For example, it told one company that its ads “omit and minimize the serious safety risks associated with OxyContin and promote it for uses beyond which [it has] been proven safe and effective.”
Overall, opioid prescriptions have quadrupled since 1999, with a similar sharp increase in opioid-related overdoses, injuries, and deaths. As many as 60 percent of returning war veterans suffer from chronic pain (compared to about 30 percent of civilian Americans). And veterans are twice as likely to die from accidental opioid overdoses as non-veterans. Furthermore, there has been an alarming rise in prescription opioid abuse. Pharmaceutical companies produce vastly more of these drugs than are needed for legitimate medical use, and much of that production is diverted to the black market. OxyContin abuse is notorious; the drug is so popular in rural America that it has become known as “hillbilly heroin.” Prescription opioid abuse and misuse cost the United States more than $60 billion each year, almost half of which is attributable to workplace costs (such as lost productivity) and half to health care costs (such as abuse treatment). Placing someone on opioids, such as OxyContin, costs by one recent estimate about $6,000 a year. This does not take into account the dollars spent on drug testing and monitoring, treatment of potential side effects, and drug rehabilitation when needed.
Doctors are to blame for most of this. Ever since morphine was isolated from opium, they have prescribed it and related drugs recklessly, often with little heed of the risks, convincing themselves and patients that each new opioid product is safer than the last. When doctors are called to account for their behavior, as happens periodically, they back away from using opioids, sometimes withholding them from patients who really need them. Sooner or later they return to the same irresponsible prescribing habits. Dr. Richard A. Friedman, a professor of clinical psychiatry and the director of the psychopharmacology clinic at the Weill Cornell Medical College, wrote in a New York Times editorial in 2015: “It is physicians who, in large part, unleashed the current opioid epidemic with their promiscuous use of these drugs; we have a large responsibility to end it.”
By 2011, many of the clinicians involved in promoting increased opioid use were publicly acknowledging that there were significant problems with reliance on these drugs for long-term management of chronic pain. In response to the rapid rise in the misuse and abuse of prescription opioids, a number of states began to restrict their availability. The federal government took action as well, subjecting manufacturers to greater scrutiny, insisting on better formulations, and requiring education of doctors about safe prescribing. For some of those in pain this has resulted in undertreatment, if opioids were a mainstay and especially if other therapies are not readily available or affordable. For doctors, it has been the continuation of an uncomfortable ride over the last century. For both patients and doctors, this situation has advanced the development and acceptance of integrative approaches to managing chronic pain.
INTEGRATIVE MEDICINE APPROACH TO MANAGING CHRONIC PAIN
A recent review of more than twenty lower-back-pain studies concluded that when exercise, acupuncture, and manipulative therapies are added to standard drug treatment, there is greater improvement in pain and function. One example of how this finding is being put into practice is the Oregon Pain Management Commission’s integrative initiative. Based on the costs and poor outcomes of a medication-focused approach, the state passed an initiative in 2016 to provide integrative therapies for chronic pain syndrome in addition to conventional care, including acupuncture, massage, manipulation, yoga, and supervised exercise and physical therapy. I hope that other states will follow Oregon’s lead and that patients, families, and health care providers will use the emerging findings to implement treatment for chronic pain—and demand insurance coverage for it. The VA has also backed away from reliance on opioids to manage chronic pain syndrome and is now actively promoting comprehensive care that includes acupuncture, yoga, mindfulness meditation, and physical therapy.
The experience of pain includes both the primary sensation of it and the brain’s interpretation of that sensation. Local anesthetics like procaine (Novocain) block the former; opioids act in the brain to modify interpretation of pain signals. With opioid-induced analgesia, a patient may report that “the pain is still there, but it doesn’t bother me” or “it is as if the pain is happening to someone else.” Under hypnosis people often make the same kinds of statements. In good subjects (those with high capacity for trance), hypnosis can induce analgesia as complete as that from any opioid—complete enough for dental procedures and even major surgery without anesthetic drugs. The mechanism for this remarkable effect might involve endogenous opioids; in any case, it demonstrates the potential of using the mind-body connection to change the experience of pain.
Apart from hypnosis, mind-body therapies useful in managing pain include visualization and guided imagery, biofeedback, breath work, meditation, and mindfulness training. An impressive body of evidence supports the efficacy of mindfulness to help patients better live with chronic pain. It allows them to focus awareness on the present moment, rather than dwell on past painful sensations or anticipate those to come. Mind-body medicine should be a major component of integrative pain management, whether or not analgesic medication is required. (In my opinion, the absence of these therapies from Oregon’s integrative pain management initiative is a glaring omission.) Yoga and various forms of relaxation training, including group relaxation, can also be helpful.
Massage, manual, and manipulative therapies (such as that offered by chiropractors and osteopathic physicians) should be considered in any cases where muscle tension, poor posture, and structural abnormalities contribute to pain. Exercise has now been confirmed to be a powerful anti-inflammatory intervention, able to reduce markers of inflammation linked to pain. Acupuncture also has a significant analgesic effect that might be mediated by endorphins.
“Biostimulation” is an umbrella term for newer therapies to reduce pain that direct electrical, magnetic, light, and sound stimulation to areas of the body. One example is transcutaneous electrical nerve stimulation (TENS), which can relieve musculoskeletal pain; TENS devices for home use are available. Also available are brain stimulation devices that deliver electromagnetic energy to shift blood flow and reduce excitability of specific areas of the brain involved in chronic pain syndrome. At the present time most can be accessed only in medical settings, but people will soon be able to get devices for home use (such as transcranial direct-current stimulators, or tDCS).
Cognitive behavioral therapy (CBT) can help chronic pain patients identify and change patterns of thought that contribute to the problem.
Group support can be tremendously helpful. Many leading medical institutions, including Cleveland Clinic and Boston Medical Center, are successfully using group settings for treating chronic pain. Additionally, some interventions, such as mindfulness meditation, can be done through an online community, allowing access for those who may not live near a class.
Diet and supplementation can help in multiple ways to reduce pain. First, as pain becomes chronic it is well known that areas of the brain that control taste and satiety change along with those that control mood. As a result, nutrient deficiency is common in chronic pain syndrome and can be worsened by long-term use of analgesic medications. Nutrients often in need of repletion include vitamin D, magnesium, omega-3 fatty acids, and coenzyme Q10 (CoQ10). Not infrequently, such deficiencies are overlooked.
An anti-inflammatory diet, known to improve overall health and reduce disease risk, can lessen any inflammatory component of pain and reduce the need for medication. In addition to emphasizing plant-based foods, the diet includes anti-inflammatory herbs and spices, such as turmeric (Curcuma longa) and ginger (Zingiber officinale).
If disturbed sleep is part of chronic pain syndrome, it must be corrected, not with additional medication but by identifying contributing factors (such as use of caffeine and other stimulants and noise or light in the bedroom) and paying careful attention to all aspects of sleep hygiene.
As medical cannabis has become legal, many patients report using it successfully to manage chronic pain, both on its own and in combination with opioids. The active components of this plant—cannabinoids—interact with opioid receptors and, at least in some individuals, make it possible to maintain the analgesic effect of opioid medications with lower doses and less frequent administration. Ongoing research is looking at which strains and preparations of cannabis are most effective for pain relief.
BOTTOM LINE
Chronic pain is fundamentally different from acute pain and cannot be managed successfully with medication alone. Opioid drugs have an important role in controlling pain in specific settings, but reliance on them to manage chronic pain syndrome can have devastating results, not only for patients but also for families and society at large.
If you or someone close to you suffers from chronic pain syndrome, it is critical to insist on an integrative treatment plan. The exact cause of the pain may not always matter as much as how that pain has affected the brain and mind-body functioning. Medication cannot address the complex psychosocial, occupational, and lifestyle dimensions of chronic pain, nor can it reverse the brain changes that underlie it.
Doctors should be supportive of this approach, as it is in line with current pain treatment guidelines. They may also help you connect with a nurse case manager, health coach, or other health care advocate who can assist you with access to non-pharmacological treatments.