I started this current series to discuss what is wrong with our country and what we need to do to fix it. While I have discussed some of the topics that I will be including in this series, they have been included in other articles. In this series I will concentrate on a single topic. This will also mean that some of the articles may be slightly shorter than my readers have grown accustomed to, however they will still be written with the same attention to detail. This series will have no set number of articles and will continue to grow as I come across additional subjects.

PAIN MANAGEMENT SPECIALTY

You are not the only one…!!! With the many practices that claim to be “Pain Management Clinics” you don’t know which provider to go to, and when to seek help, what do they do, what to expect,……Read more about what you should look for in choosing you provider…..

So many practices that claim to be “pain management clinics”, from all different educational and training backgrounds, and to add to the confusion some are not even in the medical field…!!! Some of these clinics only prescribe dangerous combination of medications, which has led to an epidemic in our community, state, and nationwide.  These “Pill Mills” have destroyed many lives and families. Unfortunately many of these clinics have given the field of  pain management a bad reputation.  

And now a days, lots of people from non medical background claim their ability to help pain patients.

With all the confusion and information provided by people, unfortunately, not all fellowship training programs provide the variety of patients and encounters needed to cover all aspects of Pain Medicine. 

Origin:

Pain Medicine is a specialty that providers can join from different backgrounds, and training. But the specialty is relatively new, started in 1978, and the first ones who started treating pain patients are anesthesiologists. 

Why Anesthesiologists are considered the leaders in the Pain Management specialty? 

Physician Anesthesiologists are medical doctors specializing in anesthesia, pain and critical care medicine, and they provide or guide nearly 90 percent of the anesthetics used in the more than 100 million procedures performed every year in the United States. 

With 12 to 14 years of education and 12,000 to 16,000 hours of clinical training, these physician specialists are the experts in managing pain. In addition, physician anesthesiologists have the extensive education and training to evaluate, diagnose, treat and manage the entire spectrum of medical conditions and patients’ needs. They also diagnose and treat potentially life-threatening complications that can happen suddenly during surgery while under Anesthesia. 

Anesthesiologists deals with all stages of Pain, at start with acute surgical pain phase, to various kind of Chronic Pain conditions. Years of research by physician anesthesiologists have led to the development of techniques and protocols that make Anesthesia and Pain Control measures safer and more effective than ever. This research is ongoing to make sure Anesthesia and Pain care continues to advance. Physician anesthesiologist works with your surgeon to develop and administer the Anesthesia and Pain care plan for your procedure, that starts before your surgery and extend beyond the Operating Room. 

What does a Pain Management Specialist do?

A pain management specialist is a physician with special training in evaluation, diagnosis, and treatment of all different types of pain. Pain is actually a wide spectrum of disorders including acute pain, chronic pain and cancer pain and sometimes a combination of these. 

Pain can also arise for many different reasons such as surgery, injury, nerve damage, and metabolic problems such as diabetes. Occasionally, pain can even be the problem all by itself, without any obvious cause at all.

As the field of medicine learns more about the complexities of pain, it has become more important to have physicians with specialized knowledge and skills to treat these conditions. 

An in-depth knowledge of the physiology of pain, the ability to evaluate patients with complicated pain problems, understanding of specialized tests for diagnosing painful conditions, appropriate prescribing of medications to varying pain problems, and skills to perform procedures (such as nerve blocks, spinal injections and other interventional techniques) are all part of what a pain management specialist uses to treat pain. 

In addition, the broad variety of treatments available to treat pain is growing rapidly and with increasing complexity. With an increasing number of new and complex drugs, techniques, and technologies becoming available every year for the treatment of pain, the pain management physician is uniquely trained to use this new knowledge safely and effectively to help his or her patients. 

Finally, competent pain management specialist plays an important role in orchestrating a treatment plan that involves specialists from various fields, integrating all means together to achieve a certain goal.….to learn more about our comprehensive pain management clinic

Myths & Facts about the Specialty:

There are many confusing and contradicting information delivered by different providers, the media, communities and friends that have left the pain suffering patients challenged and confused about the facts related to the specialty.

Here I would like to present to you some of the most common Myths surrounding the Pain Management Specialty and the Facts about it

MYTH: “PAIN MANAGEMENT IS MEANT ONLY AS A LAST RESORT FOR TREATING CHRONIC PROBLEMS WHEN EVERYTHING ELSE FAILS”

 This is the Number One myth of pain management.

As with all medicine, prevention is the key. However, when pain does occur, the best chance of alleviating pain permanently is to address it early on and aggressively. This not only allows you to return to your normal activities pain free, but also prevents your pain from becoming a chronic problem. In addition, studies suggest that in cancer patients, who receive treatment for their pain during the end of life, better pain control increases not only the quality of life, but can also increase the life expectancy.

MYTH:“IF I GO TO A PAIN CLINIC, THE ONLY THING THEY ARE GOING TO DO IS GIVE ME NARCOTICS (OPIOIDS MEDICATIONS)”

 This is a common misconception in the field of pain management. Though it is true that some pain clinics only treat pain by writing opioids and medications, here at Mission Advanced Pain Management & Spine Center we focus on diagnosing the source of your pain. By doing so, we can develop a treatment plan targeted specifically at your pain generator, giving you pain relief without the need for opioids or other medications. These medications can have serious side effects when taken for a long period of time. Though we understand that medications can play a role in managing your pain, we attempt to minimize medication usage by focusing on other modalities to treat your pain. As such, we can maximize your pain control without the use of chronic pills that can be harmful to your kidneys and liver long term.

MYTH: “IT TAKES FOREVER TO SEE A SPECIALIST. IF I’M IN PAIN NOW, MY ONLY OPTION IS TO GO TO THE ER/URGENT CARE OR TO SEE MY PRIMARY CARE PROVIDER”

 Depending on the type of insurance you have, you may need to have a referral from another provider before seeing a specialist. However, in most instances, you do NOT need a referral to be seen at Mission Advanced Pain Management & Spine Center. It is best to call our office to determine whether or not a referral is necessary. If your low back pain is new, we can typically see you within 24-48 hours. We understand that life is hard enough as it is and there is no reason for you to continue to suffer in pain. We are your urgent care for low back pain.

MYTH: “I NEED TO SEE A SPINE SURGEON FOR MY BACK PROBLEMS NOT A PAIN SPECIALIST”

 We realized that most cases will resolve with conservative therapies, but they have a better chance of resolving your pain if therapies are started early in the course of your pain. This even includes cases where you have herniated disc and even disc fragments that are pinching nerves in your low back or neck.

After your teenage years, many people begin to have degenerated, bulging discs and arthritis in the spine. The good news is that despite these changes occurring in your spine, most of the time, it does not cause any pain. However, what happens when you start having low back and/or neck pain? Once again, the good news is that the vast majority of cases do not need surgery, especially early on during the course of your pain. There are very specific criteria where surgery is necessary on an acute basis, but luckily these are few and far between. At Mission Advanced Pain Management & Spine Center, we can treat your acute pain, allowing you to get back to life as soon as possible. We are your spine pain specialists. We also know when is the appropriate time for further diagnostic studies and direct you to the appropriate providers to take care of your pain quickly and appropriately.

MYTH: “PAIN IS A NORMAL PROCESS OF AGING.”

 Aging does not have to be a painful process.

As we age, pain does become more a prevalent problem. This does not mean we must live with the pain. When pain begins to persist beyond several weeks, consider seeking an evaluation by a pain specialist. Realizing that the best treatment outcomes occur when pain is addressed early, it is recommended to not just “grin and bear it,” but to seek professional care, so that your current pain does not turn into a lifelong problem. At Mission Advanced Pain Management & Spine Center we offer treatment options that can help alleviate pain by at least 50% without needing to take medications.

If you are currently in pain and have some concerns about addressing your problem by a pain specialist, give us a call today to schedule an appointment and we will discuss your case in more details and direct you in the right direction.

MYTH:“PAIN MANAGEMENT INTERVENTIONAL PROCEDURES FOR MY BACK PAIN ARE ONLY A TEMPORARY FIX LIKE A BAND-AID ”

Well that is not accurate, the vast majority of cases can be treated, especially early on during the course of your pain. Like any other tissue in your body, it has the natural ability to heal itself on its own without surgical intervention. And what pain interventional procedure does is helping you not to be in pain by controlling the damaging inflammatory process, which in turn accelerates healing.

MYTH:“EPIDURAL STEROID INJECTIONS WILL MAKE ME GAIN WEIGHT”

Did you know that, single pain management injection dose of steroid is equivalent to far less dose than what normal body produces on daily basis from your suprarenal glands? Steroids and weight gain are of a concern mainly with Systemic (Oral or Intravenous) Steroids for systemic diseases e.g. Rheumatoid Arthritis, and is not expected to happen with Pain Management injections. We sure look into all possible side effects, but luckily weight gain is not one of them.

What should I look for in a pain management specialist? 

The most important consideration in looking for a pain management specialist is to find someone who has the training and experience to help you with your particular pain problem and with whom you feel a comfortable rapport. Since many types of chronic pain may require a complex treatment plan as well as specialized interventional techniques, pain specialists today must have more training than in the past, and you should learn about how / where your pain physician was trained and whether he or she has board certification in pain management.

The widely accepted standard for pain management education today is a fellowship (additional training beyond residency which occurs after graduating from medical school) in pain management. Most fellowship programs are associated with Anesthesiology residency training programs. There are also fellowship programs associated with neurology and physical medicine and rehabilitation residency programs. The fellowship consists of at least one year of training in all aspects of pain management after completion residency training. When a physician has become board certified in their primary specialty and has completed an accredited fellowship, they become eligible for subspecialty board certification in pain management by the American Board of Anesthesiology, The American Board of Psychiatry and The American Board of Neurology, or the American Board of Physical Medicine and Rehabilitation. These three are the only board certifications in pain management recognized by the American College of Graduate Medical Education.

In addition to learning about your pain physician’s training and board certification, you also should ask whether they have experience with your specific pain condition and what types of treatments they offer. Do they only perform procedures or do they use a multidisciplinary approach to manage and control your Pain? Who do they refer to for other treatment options such as surgery, psychological support or alternative therapies? How can they be reached if questions or problems arise? What is their overall philosophy of pain management?

Important things to look for in a pain management clinic:

• The Doctor had his training in an ACGME accredited Pain Fellowship Program http://www.acme.org
• The Doctor is Board Certified with a degree that is recognized by the American Board of Medical Specialties www.abms.org , which is the highest accreditation a physician may receive in the field of pain medicine.
• A clinic which practices a multidisciplinary approach through a comprehensive plan consisting of different treatments models.
• A clinic that can safely offer interventional as well as non-interventional treatment.
• A clinic that focuses on specific goals to control your pain, and its effects on your life.

When it comes to pain management, are you part of the problem?

Ask physicians what worries them about managing patients’ pain, and you’ll likely hear a long list of fears about choosing the right drug and dose, anxieties over potential legal hassles, and concerns about dependence and addiction.

But according to Steven Pantilat, MD, physicians face a more insidious barrier to good pain control: a reluctance to trust patients’ perceptions about pain. Dr. Pantilat, a hospitalist who is widely recognized as a guru of pain management, recalled one liver transplant patient who, post-transplant, complained of pain “only to have a nurse roll her eyes in disbelief.

That kind of response not only presents a barrier to adequate pain treatment, but it’s more common than most physicians would care to admit. “The major issue is to believe that patients have pain,” said Dr. Pantilat, who is director of the palliative care service at the University of California, San Francisco. “The good news is that the patient will tell you.”

During a presentation last spring at the annual meeting of the Society of Hospital Medicine (SHM), and in a follow-up interview with Today’s Hospitalist, Dr. Pantilat acknowledged that physicians have legitimate concerns about pain management, particularly when prescribing narcotics. But he also said that pain management, if done correctly, puts most of those concerns to rest.

Assessing pain

One of the major problems with pain treatment today, Dr. Pantilat said, is that physicians create their own barriers to adequate pain control. They may be too cautious, for example, and spend time trying to identify the source of patients’ pain, when they should be focused on getting the pain under control.

At the SHM meeting, Dr. Pantilat said that insights into physicians’ attitudes toward pain management can be found in a survey of medical oncologists published in the July 15, 1993, issue of Annals of Internal Medicine. While oncologists should be highly skilled in pain management, many said that they were concerned about their ability to make sure that patients were really in pain. They also said they worried about the potential for legal action from over-treating patients for their pain.

While physicians may be concerned about over-treating pain, Dr. Pantilat told the audience that under-treatment may be just as big a problem. He noted that states like California have addressed the issue by legislating pain-management training for providers.

It’s only natural that physicians are more comfortable treating pain that has an obvious source “think end-stage cancer “and can be stymied by chronic pain and “less directed” pain such as abdominal distress. That’s why they need to take a few simple steps to assess patients’ reports of pain severity.

For starters, Dr. Pantilat urged physicians to consider using the traditional zero-to-10 pain scale. It’s neither perfect nor highly scientific, he admitted, “but it works.”

If possible, you should also classify your patient’s pain so you know what you’re dealing with. Dr. Pantilat said that treating neuropathic pain “associated with such conditions as diabetes, HIV, alcoholism and stroke “may require a different approach and algorithm than treating muscle, bone or visceral pain. And treating pain in patients who are experiencing spiritual or somatic pain or depression will also be challenging.

Open communication

To successfully manage severe pain and keep on top of possible side effects, hospitalists need to work closely with nurses and assess patients’ response frequently. Dr. Pantilat said that ideally means every 15 minutes for the first two hours and every four hours if the management strategy appears to be working. Even patients in moderate pain should be checked every few hours, he added, to avoid breakthrough situations.

He also urged physicians to talk to patients directly about their pain treatment plan. That not only sends the message that you believe they have pain, but it gives patients in severe pain some hope that relief is on the way.

Dr. Pantilat tells patients what medicine he is prescribing and the dose they will be given. He then stresses that they must tell him how much pain they’re having- “and let him know if the dosage isn’t high enough, so he can prescribe more. He also assures them that both he and the nursing staff will respond if the plan doesn’t work.

And hospitalists who find themselves beyond their comfort zone in treating severe pain should enlist a pain management team, if one is available, or contact a pharmacist and nurses experienced in palliative care.

Therapeutic approaches: the pre-opioid approach

Another frequently cited concern is the potential for side effects from drugs like morphine. But those concerns, Dr. Pantilat said, are “typically overblown” and can lead to inadequate control.

The safe use of opioids “isn’t all that difficult,” he added, if hospitalists follow these basic principles: Start with a low dose, increase dose in response to pain, assess pain using a scale, and then increase dose by percentages if patients are having moderate to severe pain.

“You do have to start slow, and go slow [with titration],” he said, “but serious side effects and true anaphylaxis to opioids is rare.”

But before you even think about opioids, Dr. Pantilat said, here are other effective therapies you should consider. He suggested starting patients with mild to moderate pain on nonopioid medications, such as acetaminophen or nonsteroidal anti-inflammatory drugs.

For moderate to severe neuropathic pain, first-line medications include opioids, along with tricyclic antidepressants, gabapentin, tramadol hydrochloride and, as indicated, a 5 percent lidocaine patch.

“These first-line medications have shown at least a 30 percent reduction in pain intensity scores in 30 percent of patients studied,” Dr. Pantilat said. He cautioned, however, that managing neuropathic pain can be extremely challenging. “It is difficult to get them to zero [percent pain] “and often you have to combine multiple drugs.”

Opioids: How much should you prescribe?

When treating severe pain, the key with opioids is to start with a dose that’s likely to bring near-term relief of severe pain. In an opioid naive patient, start with 2-4 mg IV.

For oxycodone, the starting dose is 5-10 mg. For patients with renal disease or failure, Dr. Pantilat prefers using Dilaudid at starting doses of 0.4-1 mg IV.

Patients at the end of life may require and can tolerate 40 mg to 50 mg an hour of morphine, and a bolus dose of up to 100 mg is not out of the question for patients who have already been on high-dose morphine.

“If the patient is in severe pain, I might repeat the morphine 4 mg IV every 15 minutes,” he said. “By 15 minutes, you’ll have a good sense of how people are reacting to the dose. By 30 minutes, you’ll have seen the maximum effect.” If the patient is still in severe pain at 45 minutes, he added, “double the dose again.”

As a rule of thumb, opioids can be titrated up by 25 percent to 50 percent for moderate pain, and 50 percent to 100 percent for severe pain, Dr. Pantilat said.

“It gets more difficult for hospitalists with the higher doses,” he said. But even so, the dose-doubling principles apply. “A 100 mg morphine bolus seems huge,” Dr. Pantilat explained. “It is big, but not for the patient who’s been working up to it.”

Physicians treating post-operative patients likewise worry about high doses, but they tend to forget that pain severity will typically decrease substantially over a few days. At that point, the dose can be reduced in tandem, and hospitalists should avoid basal rate continuous infusion in these patients.

Non-opioid options

When prescribing tricyclic antidepressants, Dr. Pantilat recommended starting with a very lose dose “about 10 mg “at night, and then increasing the dose very slowly, especially with elderly patients.

“The challenge here is that in any one hospitalization you are unlikely to realize the benefits of starting that drug,” he said. “But you will at least have a few days to see what the side effects are going to be.” He noted that he prefers nortriptyline to amitriptyline because nortriptyline has fewer side effects.

Lidocaine patches are the most straightforward pain management approach, but even with patches, physicians may “under-dose.” Up to three 5 percent patches can be used simultaneously for a 12-hour period, ideally on a 12-hours-on, 12-off schedule.

Then there is meperidine, which Dr. Pantilat advised against using altogether. The drug has a short half-life, is neurotoxic and can cause seizure at doses as low as 600 mg in a 24-hour period.

“Why give someone who is in pain and is already irritable something that’s neurotoxic,” he asked, “especially when there’s a risk of seizure after repeated doses?”

Additional strategies
Dr. Pantilat also offered the following strategies for better pain control:

• Adjust dose and frequency. “We adjust dose to provide adequate pain control, so giving the same dose more frequently won’t help if someone only goes from 10 to a 7,” he said. “You have to up the dose.”

Likewise, if the patient reports that her pain has gone from a 7 to a 4 but the relief lasted less than six hours, more frequent dosing is in order.

• Use lower doses of multiple medications. Combining lower doses of several drugs may provide better control and minimize the side effects of any single drug.
• Anticipate and treat drug side effects. Common side effects include dry mouth, constipation, nausea and vomiting, and sedation or somnolence. Sedation and somnolence may improve as patients adjust to dosing “or you may need to prescribe a stimulant medication. Anticipate constipation and prescribe stool softeners and laxatives along with opioids.
• Avoid “PRN” prescribing. Don’t treat chronic, severe or anticipated pain “PRN.” That was a major factor in a celebrated 2000 verdict in which an internist was found guilty of elder abuse for under-treating a hospitalized patient’s pain with PRN meperidine. Instead, for opioid naive patients, write a regular schedule of pain medications and work with the nurse to ensure frequent assessment for dose titration.
• Document both response and function. According to Dr. Pantilat, physicians need to do a better job documenting patients’ response to pain treatment.

And even when physicians document pain scores in the chart, they’re less likely to document functional results. Be sure to note when a patient who couldn’t get out of bed is now going to physical therapy and walking because his pain is under control.

• Steroids, non-drug therapies. Other helpful strategies include using steroids intermittently as an add-on for metastatic bone disease, and combining one or more non-pharmacologic approaches with drugs. Heat, ice, massage, physical therapy and acupuncture, among other treatments, can bring relief or help patients cope better with persistent pain.

Heading off fears of addiction

Physicians also need to break down another major barrier to better pain control: their own or their patients’ fears about becoming dependent or addicted to opioids.

Dr. Pantilat cited the case of a 67-year-old woman with metastatic breast cancer admitted to the emergency department for increasing hip pain. She had been taking two tablets of acetaminophen and oxycodone (Percocet-5/325) every four hours. But as the pain increased, she upped the dose herself to two tablets every two to three hours, explaining that she didn’t want to take morphine because “it made her feel like a drug addict.”

Had the patient been adequately educated on the differences among dependence, tolerance and addiction, she might have been more open to a different therapeutic approach, Dr. Pantilat said, especially because the high doses and self-medication with acetaminophen “could have killed her liver.”

When the woman was admitted to the ward and converted to 15 mg IV of morphine every three hours, her pain was much better controlled. She was eventually discharged on 120 mg of oral long-acting morphone three times a day.

Finally, Dr. Pantilat urged hospitalists to always keep this delicate balancing act in mind: the need to weigh pain control and function. Use targeted questions on function, desired function level and pain scores, and then structure dosing to optimally manage patients who choose tolerating some pain over being “knocked out.”

“Some patients will accept a 3 pain level over a 1 level,” he said, as long as they can get some relief, think more clearly and perform daily activities. “What you are trying to do is maximize their function.”

Opioids and the Treatment of Chronic Pain: Controversies, Current Status, and Future Directions

Introduction

Opioids play a unique role in society. They are widely feared compounds, which are associated with abuse, addiction and the dire consequences of diversion; they are also essential medications, the most effective drugs for the relief of pain and suffering. Historically, concerns about addiction have apparently contributed to the undertreatment of disorders widely considered to be appropriate for opioid therapy, including cancer pain, pain at the end-of-life, and acute pain. The use of opioids for chronic non-malignant pain (CNMP) remains controversial. Following publication of reports on the safety and efficacy of opioids prescribed to small numbers of patients with CNMP and the publication of a seminal article entitled “The Tragedy of Needless Pain”, the use of opioids to treat CNMP began to be more widely practiced and incorporated into clinical guidelines. Nevertheless, despite the advances in pain medicine and the wider use of opioids for various chronic pain conditions, there is still considerable controversy surrounding the type of conditions that should be treated, whether the treatment can be generally safe and effective in selected patients, and what the clinical goals should be.

History of Opioids

The Sumerians in Mesopotamia were among the first people identified to have cultivated the poppy plant around 3400 BC. They named it Hul Gil, the “joy plant”. It eventually spread throughout the ancient world to every major civilization in Europe and Asia and was used to treat pain and many other ailments.

Developments in the 19th century transformed the practice of medicine and initiated the tension between the desire to make available the medicinal benefits of these drugs and recognition that the development of abuse and addiction can lead to devastating consequences for individuals and for society at large:

• In 1803 morphine, an opioid analgesic, was extracted from opium by Friedrich Serturner of Germany;
• Dr. Charles Wood, a Scottish physician, invented the hyperdermic needle and used it to inject morphine to relieve pain from neuralgia;
• Dr. Eduard Livenstein, a German physician, produced the first accurate and comprehensive description of addiction to morphine, including the withdrawal syndrome and relapse, and argued that craving for morphine was a physiological response.
• Diacetylmorphine (brand name heroin) was synthesized and briefly promoted as more effective and less addictive than morphine. In the early 20th century, when heroin was legally marketed in pill form, it was used by young Americans to elicit intense euphoria by crushing the heroin pills into powder for inhalation or injection.

Beginning in the twentieth century, there were many research advances and major changes in the way opioids were used for the treatment of pain and addiction. These included attempts among several nations and international organizations to control the distribution and use of opioids; the introduction of opioid maintenance therapy for the treatment of opioid addiction (first with morphine and later with methadone, LAAM and sublingual buprenorphine); the discovery of the endogenous opioids; and the recognition that pain is a debilitating and destructive disease and that opioids are essential for the treatment of many forms of acute and chronic pain.

During most of the twentieth century, the widely held perception among professionals in the United States was that the long-term use of opioid therapy to treat chronic pain was contraindicated by the risk of addiction, increased disability and lack of efficacy over time. During the 1990’s, a major change occurred, driven by a variety of medical and nonmedical factors. The use of opioids for chronic pain began to increase, showing a substantial year-to-year rise that continues today. This increased use of opioids for legitimate medical purposes has been accompanied by a substantial increase in the prevalence of nonmedical use of prescription opioids. The National Survey on Drug Use and Health reported that the number of first time abusers of prescription opioids increased from 628,000 in 1990 to 2.4 million in 2004, that emergency room visits involving prescription opioid abuse increased by 45% from 2000 to 2002, and that treatment admissions for primary abuse of prescription opioids increased by 186% between 1997 and 2002. Opioid abuse indices rose most for two frequently prescribed opioids, hydrocodone and controlled-release (CR) oxycodone. Although the increase in prescription drug abuse is likely to be multifactorial, it is likely to reflect, in part, changes in available drug formulations and prescribing practices of opioid medication. This link between increased medical use and increased abuse has driven some of the re-examination of the medical role of these drugs. The challenge, of course, is to reduce the likelihood of opioid misuse while not imposing barriers on the legitimate use of opioid medications, acknowledging both that increased abuse is probably inevitable when a psychoactive drug becomes more accessible and that attempts to control abuse can have the unintentional effects of discouraging treatment and placing severe restrictions on the medical profession.

Brief Overview of Opioids: Neurobiology and Mechanism of Action

The term opioid refers to all compounds that bind to opiate receptors. Conventionally, the term opiate can be used to describe those opioids that are alkaloids, derived from the opium poppy; these include morphine and codeine. Opioids include semi-synthetic opiates, i.e., drugs that are synthesized from naturally occurring opiates (such as heroin from morphine and oxycodone from thebaine), as well as synthetic opioids such as methadone, fentanyl, and propoxyphene. The term narcotic is a legal designation and should not be used in the clinical setting; it refers to opioids and a few other drugs that are grouped with the opioids by law enforcement.

In the United States, numerous opioids have been commercialized for oral, transdermal and intravenous administration. Oral and transdermal formulations are usually administered for pain in the ambulatory setting. These include combination products, such as those containing hydrocodone and acetaminophen (Vicodin®, Lorset®) or ibuprofen (Vicoprofen®), tramadol and acetaminophen (Ultracet®), oxycodone and acetaminophen or aspirin (Percocet® or Percodan®), and those containing codeine and acetaminophen or aspirin. The single entity formulations on the market include those containing morphine (Avinza®, Kadian®, MS Contin®, MSIR®), oxycodone (OxyContin®), fentanyl (Duragesic®, Actiq®, Fentora®), hydromorphone (Dilaudid®), oxymorphone (Opana®), and methadone.

Opioids act by binding to specific proteins, called opioid receptors. Receptors are widely distributed. Those involved in pain modulation are situated in both the central nervous system and the peripheral nervous system. These receptors also bind endogenous opioid peptides (endorphins), which are involved in pain modulation and numerous other functions in the body. Among these functions are those mediated by deep structures of the brain, which are involved in the modulation of reinforcement and reward mechanisms, mood and stress. Opioid receptors are also found on cells from the immune system. In studies with rats, activation of these receptors with morphine is associated with varied effects, including sensitization of afferent nerves to noxious stimuli.

When an opioid given for pain binds to receptors, analgesia may be accompanied by any of a diverse array of side effects related to the activation of receptors involved in other functions. These may include effects mediated by peripheral or by peripheral and central mechanisms, such as reduced peristalsis (leading to constipation) and itch, or primary central nervous system effects, such as miosis, (pupillary constriction) somnolence, mental clouding, and respiratory depression. Central mechanisms also lead to changes associated with hyperalgesia and decreased responsiveness to opioids (tolerance) and it has been speculated that opioid-induced hyperalgesia may be a clinically-relevant phenomenon leading to increased pain in some situations. Activation of other central nervous system pathways by opioids also may produce mood effects, either dysphoria or euphoria.

Presumably, binding to those receptors involved in reinforcement and reward also occurs whenever an opioid is taken. In most individuals, when opioids are taken to treat pain, there appears to be no overt effect from change in these systems. In some cases, however, powerful reinforcement occurs, expressed as efforts to repeat the administration and these reinforcing outcomes may be associated with craving and with positive mood effects such as euphorigenic or pleasurable effects. These outcomes, which are uncommon but potentially serious when they occur (driving the development of an addictive pattern of use), can occur in the presence or absence of pain. Although these effects could be associated with iatrogenic addiction, they appear to be rare in patients who do not have risk factors suggesting the existence of the biological substrate for opioid-induced craving.

Although several types of opioid receptors exist (e.g., mu, kappa and delta), opioid drugs largely produce their analgesic and reinforcing effects via activation of the mu opioid receptor; thus, opioids used for pain are often described as, “mu agonists”. Mu drugs that have the ability to fully activate opioid receptors (e.g., higher doses produce greater receptor activation in a dose-dependent manner) are referred to as opioid agonists or full mu agonists (such as morphine, oxycodone and methadone). Those opioids that occupy, but do not activate, receptors are referred to as opioid antagonists (e.g., naltrexone, naloxone); they can reverse the effects of mu opioid agonists. Those opioids that either have a low intrinsic activity at the mu receptor, or are agonists at another receptor and antagonists at the mu receptor are called agonist-antagonist drugs. Those with a low intrinsic activity are called partial opioid agonists and are characterized by a ceiling on most agonist activity, such that increases in dose will increase the drug’s physiological and subjective effects only to a certain level and further dose increases produce no additional effects.

These differences in mu receptor interactions are clearly related to the clinical use of opioid drugs and their abuse liability. Agonist-antagonist drugs are less attractive than pure mu agonists to individuals with addiction and no pain. Although other biochemical and molecular processes are presumably relevant to variation in these effects, relatively little is known about the interactions among these processes in humans.

The clinical use of opioid drugs is influenced by a variety of other characteristics, including pharmacokinetics. With the notable exception of methadone and buprenorphine, most opioids have relatively short half-lives and this has necessitated the development of new delivery systems designed to provide prolonged effects and a longer dosing interval.

Clinically-relevant physical dependence and tolerance (see below) may occur with short-term or long-term use of an opioid compound, particularly a pure mu agonist. These phenomena, which vary greatly in the clinical setting, represent neuro-adaptational processes. The neurophysiology of physical dependence and tolerance are closely related to each other and to the phenomenon of opioid-induced hyperalgesia. The possibility that opioid administration, particularly at relatively high doses, may lead to increased pain has contributed to the controversy about opioid therapy for non-cancer pain, notwithstanding the limited evidence that this phenomenon occurs in clinical settings.

Brief Overview of Chronic Pain

Chronic pain has been described as pain that has persisted for at least 1 month following the usual healing time of an acute injury, pain that occurs in association with a nonhealing lesion, or pain that recurs frequently over a period of months. In most clinical and research reports, chronic pain is typically defined as pain that has persisted for at least 3 months.

The prevalence of chronic pain in the general population is believed to be quite high, although published reports have varied greatly. Cautious cross-national estimates of chronic pain range from 10% to close to 20%, which would represent 30 to 60 million Americans. A national survey of 35,000 households in the US, conducted in 1998, estimated that the prevalence among adults of moderate to severe non-cancer chronic pain was 9%. A large survey (N=18,980) of general populations across several European countries reported that the prevalence for chronic painful physical conditions was 17.1%.

Chronic pain is a highly complex phenomenon, which may or may not be primarily driven by tissue injury. Conventionally, the most common forms of chronic pain are divided into those labeled “nociceptive”, or pain caused by ongoing stimulation of pain receptors by tissue damage, and those labeled “neuropathic”, or pain presumed to be related to damage to or dysfunction of the peripheral or central nervous system. These categories of pain simplify a complex reality in which both acute and chronic pain are induced by multiple peripheral and central mechanisms, which continually interact with each other and with numerous pain modulating systems. The perturbations that ultimately results in pain perception are caused by neurophysiological processes and other related systems. For example, recent evidence has begun to highlight the role of neuroimmune activation following a tissue injury as an important mechanism in the development of chronic pain. The role of cytokines and other inflammatory mediators is obvious in inflammatory nociceptive pains, such as some types of arthritis, but new data suggest an equally salient role in the development of chronic neuropathic pain associated with central sensitization of neural pathways following peripheral injury.

All chronic pain is profoundly influenced by psychological processing and responses. Pain severity and pain-related functional impairment are often found to be associated with psychological and social factors, and patients with identical diseases associated with pain, such as degenerative disk disease, may vary greatly in their reports of pain severity and pain behaviors. There is an extensive literature documenting the importance of operant conditioning factors and cognitive-behavioral factors in the maintenance of chronic pain behaviors.

Chronic pain also is influenced by psychosocial and psychiatric disturbances, such as cultural influences, social support, comorbid mood disorder, and drug abuse. Classic studies of pain behavior indicate that cultural differences in the beliefs and attitudes towards pain and the social/environmental context of the pain have a significant impact on pain behaviors.

The contribution of psychological, social and psychiatric factors should not lead to the conclusion that a pain syndrome is primarily psychogenic. Pain related exclusively or primarily to psychological factors occurs, but is far less prevalent than pain associated with organic processes that are powerfully influenced by psychosocial mediators and psychiatric comorbidities.

The “pattern of suffering” or the pain-related disability that often occurs in concert with persistent pain commonly touches on all domains of function. Patients with chronic pain may demonstrate pain-related interference with ability to perform usual activities at home, work, or school; maladaptive or dysfunctional behaviors, social isolation, and poor sleep patterns; and frequent health care utilization. The recognition that acute pain can compromises health has led major medical associations and accreditation committees to designate pain severity as a “fifth vital sign”, along with blood pressure, temperature, heart rate, and respiration. Further recognition of the increased interest in the assessment and management of pain is underscored by the U.S. Federal Law (Pain Relief Promotion Act of 2000) that declared the first decade of the 21^st century as the Decade of Pain Control and Research.

Chronic pain is a major public health problem, which is associated with devastating consequences to patients and families, a high rate of health care utilization, and huge society costs related to lost work productivity. The existing treatments for chronic pain are unable to address the problem and better therapies are urgently needed. The need for these therapies is the backdrop for the expanding use of opioid drugs. An extensive clinical experience indicates that long-term opioid therapy is able to help selected patients have a better quality of life, less use of health care, and improved productivity. The medical community is no longer debating the reality of these outcomes, but rather, is now focused on a more fruitful debate about patient selection and the benefits and burdens of these drugs in varied subpopulations. Whether the frame of reference is the individual patient and family, or society-at-large, the issue is about balancing the potential benefits of these drugs in the large and diverse population with chronic pain with its potential risks.

Terminology of Opioid Abuse: Dependence, Tolerance, Addiction

Concerns that addiction is a frequent iatrogenic consequence of the medical use of opioids may partially be attributed to confusion over terminology, as a well as failure to recognize that both addiction and chronic pain have a multifactorial etiology. In an effort to develop universal agreement on terminology related to addiction, the American Academy of Pain Medicine (AAPM), the American Pain Society (APS), and the American Society of Addiction Medicine (ASAM) approved a consensus document that clarified this terminology.

According to the consensus document, tolerance is defined as a decreased subjective and objective effect of the same amount of opioids used over time, which concomitantly requires an increasing amount of the drug to achieve the same effect. Although tolerance to most of the side effects of opioids (e.g., respiratory depression, sedation, nausea) does appear to occur routinely, there is less evidence for clinically significant tolerance to opioids– analgesic effects. For example, there are numerous studies that have demonstrated stable opioid dosing for the treatment of chronic pain and methadone maintenance for the treatment of opioid dependence (addiction) for extended periods. However, despite the observation that tolerance to the analgesic effects of opioid drugs may be an uncommon primary cause of declining analgesic effects in the clinical setting, there are reports (based on experimental studies) that some patients will experience worsening of their pain in the face of dose escalation. It has been speculated that some of these patients are not experiencing more pain because of changes related to nociception (e.g. progression of a tissue-injuring process), but rather, may be manifesting an increase in pain as a result of the opioid-induced neurophysiological changes associated with central sensitization of neurons that have been demonstrated in preclinical models and designated opioid-induced hyperalgesia. Analgesic tolerance and opioid-induced hyperalgesia are related phenomena, and just as the clinical impact of tolerance remains uncertain in most situations, the extent to which opioid-induced hyperalgesia is the cause of refractory or progressive pain remains to be more fully investigated. Physical dependence represents a characteristic set of signs and symptoms (opioid withdrawal) that occur with the abrupt cessation of an opioid (or rapid dose reduction and/or administration of an opioid antagonist). Physical dependence symptoms typically abate when an opioid is tapered under medical supervision. Unlike tolerance and physical dependence which appear to be predictable time-limited drug effects, addiction is a chronic disease that “represents an idiosyncratic adverse reaction in biologically and psychosocially vulnerable individuals”.

The distinction between physical dependence and addiction is not always made clear in the pain literature. Most patients who are administered opioids for chronic pain behave differently from patients who abuse opioids and do not ever demonstrate behaviors consistent with craving, loss of control or compulsive use. Of course, pain and addiction are not mutually exclusive and some patients who are treated for pain do develop severe behavioral disturbances indicative of a comorbid addictive disorder.

Some patients who are treated with opioids for pain display problematic behaviors that, on careful assessment, do not reflect addiction, but rather, appear to relate to a different process. This may be another psychiatric disorder associated with impulsive drug-taking, an unresolved family issue, a disorder of cognition, or criminal intention. In addition, there appear to be some patients who engage in problematic behaviors related specifically to desperation about unrelieved pain. The term pseudo-addiction was coined to describe the latter phenomenon.

Behaviors that may represent pseudo-addiction and behaviors that reflect addiction or some other serious psychopathology can occur simultaneously, and presumably, one type of phenomenon may incite the others. The diagnosis of these and other conditions may be challenging and requires a careful assessment of clinical phenomenology, specifically a range of drug-related behaviors during treatment with a potentially abusable drug.

The term aberrant drug-related behaviors has been used to indicate the broad array of problematic nonadherence behaviors, the nature of which is uncertain until a diagnosis can be developed based on astute clinical assessment. Some aberrant drug-related behavior strongly suggests the existence of addiction. These may include the use of alternative routes of administration of oral formulations (e.g., injection or sniffing), concurrent use of alcohol or illicit drugs, and repeated resistance to changes in therapy despite evidence of adverse effects; examples of aberrant behavior less suggestive of addiction are drug hoarding during periods of reduced symptoms, occasional unsanctioned dose escalation, and aggressive complaining about the need for more drugs.

Distinction between Withdrawal and Chronic Pain

Because addiction is associated with psychological distress and physical discomfort in the form of opioid withdrawal symptoms, it may be difficult to distinguish primary chronic pain complaints from withdrawal pain. Withdrawal also may have the potential to increase baseline pain related to other processes. For example, based on anecdotal evidence from chronic pain patients, withdrawal from opioids can greatly increase pain in the original pain site. These phenomena suggest the need to carefully assess the potential for withdrawal during long-term opioid therapy (e.g, at the end of a dosing interval or during periods of medically-indicated dose reduction).

These phenomena notwithstanding, there also is evidence that experienced drug abusers are able to distinguish withdrawal pain from chronic pain. For example in studies of methadone maintenance patients, both the phenomenology and correlates of chronic pain were different than for withdrawal pain. Chronic pain is typically localized (e.g., back pain, headache) and persists (although with varying degrees of severity) for long periods of time. Although certain subjective experiences of withdrawal (e.g., muscle ache) are similar to some distinct pain syndromes, other withdrawal experiences such as yawning, sweating and hot and cold flashes are likely to be more commonly associated with subjective drug withdrawal than with primary pain conditions. Moreover, the constellation of words used to describe withdrawal pain is likely to be different than words used to describe other painful disorders. Qualitative studies of addicts going through withdrawal typically refer to the experience as “being sick” (similar to a moderate to severe flu-like illness) and not as representing a distinct pain. The subjective experience of withdrawal can be validly measured with an instrument such as the Subjective Opiate Withdrawal Scale. Withdrawal from short-acting opioids, such as heroin, is typically short-lived; physical symptoms are likely to reach their maximum intensity over a 36–72 hour period and to reduce in intensity after that.

Co-occuring Chronic Pain and Opioid Addiction

The prevalence of addictive disorders among chronic pain patients is difficult to determine. One 1992 literature review found only seven studies that utilized acceptable diagnostic criteria and reported that estimates of substance use disorders among chronic pain patients ranged from 3.2% – 18.9%. A Swedish study of 414 chronic pain patients reported that 32.8% were diagnosed with a substance use disorder. In two US studies, 43 to 45% of chronic pain patients reported aberrant drug-related behavior; the proportion with diagnosable substance use disorder is unknown. All these studies evaluated patients referred to pain clinics and may overstate the prevalence of substance abuse in the overall population with chronic pain.

A relatively high prevalence of substance abuse disorders among persons with chronic pain can also be inferred by the high co-occurrence of these two disorders. There have been several reports that the prevalence of chronic pain among persons with opioid and other substance use disorders is substantially higher than the pain prevalence found in the general population.

Opioid Treatment for Chronic Pain

Opioid therapy is the mainstay approach for the treatment of moderate to severe pain associated with cancer or other serious medical illnesses. Although the use of opioid analgesics for the treatment of CNMP has been increasing in recent years and has been endorsed by numerous professional societies, the use of opioids remains controversial due to concerns about side effects, long-term efficacy, functional outcomes, and the potential for drug abuse and addiction. The latter concerns are especially evident in the treatment of CNMP patients with substance use histories.

Other concerns that may contribute to the hesitancy to prescribe opioids may be related to perceived and real risks associated with regulatory and legal scrutiny during the prescribing of controlled substances. These concerns have propelled extensive work to develop predictors of problematic behaviors or frank substance abuse or addiction during opioid therapy. Questionnaires to assist in this prediction and monitoring have been developed and used in research and field trials. Examples include the Prescription Drug Use Questionnaire; the Pain Assessment and Documentation Tool and the Current Opioid Misuse Measure. These instruments are not used in practice settings at this time.

Narrative reports on the use of opioids for CNMP have underscored the effectiveness of opioid therapy for selected populations of patients and there continues to be a consensus among pain specialists that some patients with CNMP can benefit greatly from long-term therapy. This consensus, however, has received little support in the literature. Systematic reviews on the use of opioids for diverse CNMP disorders report only modest evidence for the efficacy of this treatment. For example, a review of 15 double-blind, randomized placebo-controlled trials reported a mean decrease in pain intensity of approximately 30% and a drop-out rate of 56% only three of eight studies that assessed functional disturbance found improvement. A meta-analysis of 41 randomized trials involving 6,019 patients found reductions in pain severity and improvement in functional outcomes when opioids were compared with placebo. Among the 8 studies that compared opioids with non-opioid pain medication, the six studies that included so-called “weak” opioids (e.g., codeine, tramadol) did not demonstrate efficacy, while the two that included the so-called “strong” opioids (morphine, oxycodone) were associated with significant decreases in pain severity. The standardized mean difference (SMD) between opioid and comparison groups, although statistically significant, tended to be stronger when opioids were compared with placebo (SMD = 0.60) than when strong opioids where compared with non-opioid pain medications (SMD = 0.31). Other reviews have also found favorable evidence that opioid treatment for CNMP leads to reductions in pain severity, although evidence for increase in function is absent or less robust. Little or no support for the efficacy of opioid treatment was reported in two systematic reviews of chronic back pain. Because patients with a history of substance abuse typically are excluded from these studies, they provide no guidance whatsoever about the effectiveness of opioids in these populations.

Adding further to the controversy over the utility of opioid analgesics for CNMP is the absence of epidemiological evidence that an increase in the medical use of opioids has resulted in a lower prevalence of chronic pain. Noteworthy is a Danish study of a national random sample of 10,066 respondents. Denmark is known for having an extremely high national usage of opioids for CNMP and this use has increased by more than 600% during the past two decades. Among respondents reporting pain (1,906), 90% of opioid users reported moderate to very severe pain, compared with 46% of non-opioid users; opioid use was also associated with poor quality of life and functional disturbance.

Although this epidemiological study may be interpreted as demonstrating that opioid treatment for CNMP has little benefit, the authors acknowledge that these disquieting findings do not indicate causality and could be influenced by the possibility of widespread undertreatment, leading to poorly managed pain. This latter interpretation is supported by a commentary on the Ericksen et al. study. Keane notes that among the 228 pain patients receiving opioids only 57 (25%) were using strong opioids, while the remainder was using weak opioids. European (as well as United States) clinical guidelines generally recommend long-acting formulations of strong opioids for the treatment of chronic moderate to severe pain, which may be supplemented with short-acting opioids for breakthrough pain.

The possibility of inappropriate opioid treatment is further supported by another Danish study that assigned pain patients who were on opioid therapy to either a multidisciplinary pain center (MPC) or to general practitioners (GP) who had received initial supervision from the MPC staff. At intake, a substantial number of patients in both groups were apparently receiving inappropriate opioid therapy for chronic pain (60% were being treated with short-acting opioids and 49% were taking opioids on demand). At the 12 month follow-up, 86% of MPC patients were receiving long-acting opioids and 11% took opioids on demand. There was no change in the administration pattern in the GP group. These findings suggest that a significant proportion of opioid-treated CNMP patients may be receiving inappropriate opioid treatment and that educating general practitioners in pain medicine may require more than initial supervision.

It is generally acknowledged that there is a wide degree of variance in the prescribing patterns of opioids for chronic pain. Some opioid treatment practices persist despite evidence that they might be harmful or have little benefit, such as the over-prescribing of propoxyphene among the elderly. Nursing home patients being treated with opioids have been found to be inadequately assessed for pain and to be more likely treated with short-acting rather than long acting opioids. A substantial number of physicians are reluctant or unwilling to prescribe long-acting opioids to treat CNMP, even when it may be medically appropriate.

Controversy about the long-term effectiveness of opioid treatment also has focused on the potential clinical implications of opioid-induced hyperalgesia. As noted earlier, exposure to opioids can result in an increased sensitivity to noxious stimuli in animals, and an increased perception of some types of experimental pain in humans. Anecdotal reports of hyperalgesia occurring with very high or escalating doses of opioids has been viewed as a clinical correlate of these experimental findings. The extent to which this phenomenon is relevant to the long-term opioid therapy administered to most patients with chronic pain is unknown. Although experimental evidence suggests that opioid-induced hyperalgesia might limit the clinical utility of opioids in controlling chronic pain, there have been no reports of observations in the clinical literature to suggest that it should be a prominent problem. More research is needed to determine whether the physiology underlying opioid-induced hyperalgesia may be involved in a subgroup of patients who develop problems during therapy, such as loss of efficacy (tolerance) or progressive pain in the absence of a well defined lesion.

Outcome studies of long term use of opioids are compromised by methodological limitations which make it difficult to acquire evidence of efficacy. Methodological limitations may be unavoidable because of the ethical and practical challenges associated rigorous studies such as randomized controlled trials. Guidelines for opioid therapy must now be based on limited evidence; future evidence may be acquired by utilizing other study designs such as practical clinical trials. These studies should include at least three criteria to reflect a positive treatment response: i.e., reduction of pain severity (derived from subjective reports or scores on pain scales), recovery of function (improved scores on instruments that measure some aspect of function), and quality of life.

Guidelines for the use of opioids for the treatment of chronic pain have been published, and recent guidelines have emphasized the need to initiate, structure and monitor therapy in a manner that both optimizes the positive outcomes of opioid therapy (analgesia and functional restoration) and minimize the risks associated with abuse, addiction and diversion. These guidelines discuss patient selection (highlighting the likelihood of increased risk among patients with prior histories of substance use disorders), the structuring of therapy to provide an appropriate level of monitoring and a presumably lessened risk of aberrant drug-related behavior, the ongoing assessment of drug-related behaviors and the need to reassess and diagnose should these occur, and strategies that might be employed in restructuring therapy should aberrant behaviors occur and the clinician decide to continue treatment. They also note that therapy should be undertaken initially as a trial, which could lead to the decision to forego more therapy, and that an “exit strategy” must be understood to exist should the benefits in the individual be outweighed by the burdens of treatment.

The relatively recent recognition that guidelines for the opioid treatment of chronic pain must incorporate both the principles of prescribing as well as approaches to risk assessment and management may represent an important turning point for this approach to pain management. Acknowledging that prescription drug abuse has increased during the past decade, a period during which the use of opioid therapy by primary care physicians and pain specialists has accelerated, pain specialists and addiction medicine specialists now must collaborate to refine guidelines, help physicians identify the subpopulations that can be managed by primary care providers, and discover safer strategies that may yield treatment opportunities to larger numbers of patients.

Treating Patients with Addictive Disorders

Safe and effective pain treatment is especially important for persons with a drug use history because inadequate treatment or lack of treatment for pain may have problematic consequences, such as illicit drug use (e.g., heroin), misuse of prescription opioids and other pain medications (e.g., benzodiazipines), psychiatric distress, functional impairment and a tendency for health providers to attribute pain complaints and requests for pain medication to an addictive disorder rather than to a pain disorder. Undertreatment of pain among addicted persons may lead to the adverse medical, social and personal consequences associated with continued drug-seeking behavior. Pain complaints may be most problematic among persons with opioid addiction, as this group may have lower tolerance for pain than other addicted populations. Pain and opioid addiction may be further intertwined among persons who have a history of abusing controlled opioid pain medications, such as oxycodone or hydrocodone.

A Possible Role on the use of Buprenorphine for the Treatment of Chronic Pain

Increasing interest in developing clinical protocols for opioid treatment of chronic pain in the population with substance abuse histories has highlighted the role of opioid medications that may have lower abuse potential. One medication that is beginning to be examined is buprenorphine, a partial opioid mu agonist that is well recognized as an analgesic. In 2002, a sublingual tablet (both in mono form – Subutex® – and combined with naloxone – Suboxone®) was approved by the U.S Food and Drug Administration as a Schedule III medication for the treatment of opioid dependence. In numerous controlled clinical trials, it has been demonstrated to be highly efficacious in reducing illicit opioid use and promoting treatment retention among opioid abusers. In opioid addicts, it suppresses the craving and withdrawal symptoms associated with opioid use and also blocks the euphoric effects of subsequent opioid use.

As a partial mu-agonist, buprenorphine has a ceiling effect on its agonist activity. It is less likely than a full agonist to cause respiratory depression in opioid-naïve patients. This property of buprenorphine increases its safety profile by reducing the risk of accidental overdose. The partial agonism of buprenorphine would presumably yield a ceiling effect for analgesia as well, which would limit the clinical use of the drug in pain management, but there is some question about the extent of this ceiling effect in practice.

Although the combination buprenorphine/naloxone tablet (Suboxone) may precipitate withdrawal in opioid-tolerant persons if it is injected, making it relatively unattractive for diversion, there is nevertheless evidence of diversion, as would be expected with any psychoactive drug that has hedonic properties. Rates of abuse are relatively low compared to full mu agonists and buprenorphine rarely is endorsed as a primary drug of abuse.

In Europe, a transdermal formulation of buprenorphine has been approved for the treatment of chronic pain. In post-marketing surveillance studies and in a multicenter randomized controlled clinical trial, the transdermal patches were reported to be effective and well-tolerated in the treatment of cancer and non-cancer chronic pain. A transdermal formulation of buprenorphine is not presently available in the United States.

The off-label use of sublingual buprenorphine tablets to treat chronic pain has been described in two clinical reports, one describing its use in a series of chronic pain patients who were responding poorly to other opioid analgesics and the other describing the response of patients with both pain and addiction. In both of these reports, the authors reported that their patients were successfully treated with buprenorphine, e.g., pain relief and improved mood and functioning.

In a similar manner, two earlier publications describe the open-label use of the parenteral formulation of buprenorphine administered sublingually to treat patients with chronic pain. Although most patients were followed up for less than one month, both studies reported good analgesia and low incidence or time-limited unwanted side effects. There is also evidence from several preclinical studies and one study with human subjects that, in contrast to pure mu-agonists, buprenorphine exerts a lasting anti-hyperalgesic effect. The transdermal trials conducted in Europe, the anecdotal reports of sublingual administration in North America, and buprenorphine’s comparatively high safety profile suggest that it would be valuable to systematically study buprenorphine as a treatment of pain in patients with substance use disorders.

Conclusion

Opioids are among the most effective medications for moderate to severe pain. Although there is a consensus on their utility as a treatment for chronic cancer pain, their long-term use for chronic non-malignant pain remains controversial. Several medical professional organizations acknowledge the utility of opioid therapy and many case series and large surveys report satisfactory reductions in pain, improvement in function and minimal risk of addiction. However, the clinical trials that have been conducted do not provide adequate evidence of long-term effectiveness. Despite the consensus of pain specialists, and the eminently ethical and medically justified commentaries to consider opioid therapy in the armamentarium of treatments for moderate to severe pain, there is concern that the pendulum has swung from undertreatment to overtreatment. This controversy is enhanced by the increased prevalence of prescription opioid abuse, which has developed concomitantly with an increase in opioid administration in the clinic. The resolution of this controversy will require much more research and the acceptance of treatment guidelines that recognize the dual obligations of the prescriber: to optimize the balance between analgesia and side effects, and promote other favorable outcomes, while concurrently assessing and managing the risks associated with abuse, addiction and diversion. At this juncture, it is important that the opioid treatment debate evolve from a discussion focused on “too little” or “too much” to one focused on identification and training of best treatment practices. Improvement in opioid therapy can occur through research and training to aid practitioners to determine the appropriate patient subpopulations and treatment protocols to achieve satisfactory outcomes.

Finally, it is imperative to advance a research agenda that leads to the identification of methods that would enhance pain relief while reducing the likelihood of addiction and other adverse events when opioids are selected for therapy. This should include the testing of novel medications that may be safer or more differentially effective for select treatment populations (as the proposal to test buprenorphine with high risk patients, discussed above) and the evaluation of treatment protocols incorporating risk management techniques.

Resources

todayshospitalist.com, “When it comes to pain management, are you part of the problem?” By  Bonnie Darves; abovepain.com, “PAIN MANAGEMENT SPECIALTY.”; ncbi.nlm.nih.gov, “Opioids and the Treatment of Chronic Pain: Controversies, Current Status, and Future Directions.” By Andrew Rosenblum, Lisa A. Marsch, Herman Joseph, and Russell K. Portenoy;

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