WHAT IS PAIN?

“The art of life is the art of avoiding pain; and he is the best pilot, who steers clearest of the rocks and shoals with which it is beset.”
Thomas Jefferson in a letter to Maria Cosway,
12 October 1786.

You know something is wrong, but you can't quite figure it out. The light is so bright. Even with your eyes closed you can see the nearly blinding light through your eyelids. You try to open your eyes and everything appears blurry. You try to focus, but can't make out the details around you. Lying on your back in this uncomfortable bed you can't even move your arms. You try to speak, but no words come. You see a silhouette moving against the background of the light, but you can't make out who or what it is. You keep trying to make sense out of this and out of the awful feeling coming from your chest. It's like a thousand nails driven into your chest. Every breath you take makes the pain that much worse. You try to move your head and your throat feels like there is a knife stuck into it. The more you try to clear your mind to understand what is occurring, the more you hurt. You feel terrible pain in the center of your chest, in your throat, in your arms, and you realize that your arms are tied to the bed. You want to struggle, to free yourself, but every movement you make intensifies one of the many painful sites. You don't understand why this is happening to you, until the silhouette leans over and says, “Don't struggle, you are doing fine, your surgery went very well.” Then you realize that you have awakened from your coronary bypass surgery. You have survived. You try to get the silhouette's attention. Looking over you, she says, “I can give you some more medicine if you are hurting. Would you like some more medicine?” She smiles, takes some of the IV tubing in her hand and injects something into it. Within a minute you are floating again and the terrible pain is gone. The silhouette must be an angel and this must be heaven.

Many years later, after a long struggle with cancer, you hurt everywhere. It is just an ordeal for you to change position in bed. When the home health nurses come, they do things that cause you to hurt more. They want to change your linen, give you a sponge bath, wash your hair and treat your bedsores. You know they mean well, but the movement, any movement, is so awful. The multiple fractures and the many metastases cause even the slightest movement to feel as if you are being run through a meat grinder and tossed into a furnace. It takes hours after they leave just to get comfortable again. Why won't they just leave you alone and stop doing these things. Why won't they give you enough medicine to get rid of the awful pain? Each time they come, you ask if there is more medicine or better medicine you can take. Most of them let you take a little bit more of the “rescue medicine,” but your physician doesn't want you to get addicted. He doesn't want you to use too much of the medicine now, because the pain might be worse later on. The nurses have to follow your physician's orders. “Besides, aren't you taking enough medicine now? You are already up to 160 mg of the controlled-release medicine twice daily. Most people are very comfortable on that amount,” one nurse says. “You will need the medicine later when the pain gets worse.” You ask, “When will it be late enough to get more medicine to relieve the pain?”

Has it been 5 years and several months since the accident? You try to forget that terrible night when the drunk driver hit your car. There hasn't been a day since then that you haven't been in agony. You can't lift anything more than a few pounds, can't do chores around the house, and can't even dress yourself without great discomfort. You aren't going to learn to live with the pain as the doctors are telling you to do. Why do you want to live with pain anyway? Why can't the doctors give you something strong enough to control the pain? What do they mean about not using narcotics because they could ruin your life? What is so bad about taking narcotics to relieve pain so you can work? So what if you get addicted? What's being addicted anyway? At least the addicts get out of bed and do things–you can't. Who decides that you don't need medication anyway? Why don't your views matter? This has to stop . . . . right now.

PAIN IS UNIQUE AND PERSONAL

No two people experience a similar painful event in the same way. While surgical incisions may be the same in their length, the mass of tumors may be similar, or the number of fractures equal after a traumatic injury, people bring unique personal circumstances to their pain experience. While generalities about pain may be drawn, it is certain that every patient experiences his or her pain differently. There is nothing more untruthful when it comes to understanding pain than the old saying “one size fits all.” It is not true for cars, clothes, or houses and it is certainly not true for patients suffering from painful conditions. Sadly, patients should not want to die because their physicians are reluctant to use adequate amounts of effective opioids to relieve pain.¹

Despite our best efforts to fully understand all of the mechanisms underlying the experience of pain, we often fail to appreciate the duality of it. Pain is not just some isolated sensory event, but always comes richly invested with emotions. The range of these emotions runs from anger to anxiety, depression to despair, and frustration to nihilism. We cannot just focus on the raw intensity of pain. We must see its fuller meaning, especially when pain endures and is part of a larger clinical process, such as cancer, or associated with chronic disability.

We can agree that pain “hurts,” that it is “bothersome,” and that it limits the ability of most people to do the various activities of daily living necessary for productivity. We may use descriptive language to help each other understand what the pain of another person might be like: “The pain is killing me,” “I am being tortured by the pain,” “I can't stand this pain any more.” Language often fails us when we try to describe pain, because the words used do not fully express the horror of the situation. Words such as mild, moderate, and severe give us a broad understanding about pain, but vicious, overwhelming, incapacitating, and soul-stealing tell us even more about the pain experience. The reason we must use language or some other means to evaluate pain complaints is that we have no established chemical markers, imaging methods, or neurophysiological tests to accurately assess or measure pain.²

MEASURING PAIN

For practitioners to objectify pain to make necessary treatment decisions, we must attempt to measure a purely subjective experience. Pain is always subjective by definition and has been defined as an “untestable hypothesis” by Scott Fishman, MD because we can never absolutely measure it objectively. Patients silently tolerate unrelieved pain because we routinely fail to thoroughly assess them. We assess their pain to make decisions about the types of treatment provided.³ Pain scales are useful because they help our patients communicate to us their pain intensity, and ultimately guide our therapy.²

Fig 1.—Analog Pain Scales.

We craft scales to quantify the intensity of pain being experienced, and then plot these derived numbers on graphs to follow trends over time and to decide if improvement is occurring. Using a simple 10 cm line, we anchor one end of the line using the label “no pain” and the other end with the label “the worst pain you could ever imagine.”⁴ Pondering this continuum, most patients quickly locate their pain intensity somewhere on the line (Figure 1). This is the visual analog scale (VAS) frequently mentioned in research protocols and medical reports having to do with pain.⁵ This open-ended scale allows patients to describe their pain in great detail, as there are no clear points along the continuum other than the two anchoring end points. Measuring from the left side (no pain) toward the right side (worst pain imagined), practitioners obtain pain intensity scores between 0 and 100 (if millimeter distances are used).

If the same 10 cm line has anchoring points of 0 and 10, the scale would be a numerical analog scale (Figure 1). While quick to use, patients tend to select the whole integer numbers along the scale and consequently do not provide as much subtle detail about their pain intensity as we often obtain using the visual analog scale. Most adults and children over the age of 7 can have their pain intensity assessed using either the numerical scale or the visual analog scale.²

If we draw a 10 cm line with “no pain” and “worst pain imagined” anchoring terms not just on the ends, but other descriptive terms at several other places along the line using other words to describe pain, we would have a descriptive analog scale (Figure 1). This scale is the more limited in being able to show the variation in pain intensity over time because it usually only has five real choices, but has the advantage of being very quick to administer.

Although completion of pain assessment scales may be viewed as time-consuming by some practitioners, the use of these scales is invaluable clinically.⁶ It does not really matter what system of measurement we use to assess pain intensity, but it does matter that we believe what our patients tell us when they report their pain intensity to us. These scales are useless if we intend to debate with our patients what points they select, or try to talk our patients out of the intensities they report.^2,7

DO WE BELIEVE WHAT WE ARE TOLD ABOUT PAIN?

“Pain is real when you get other people to believe in it. If no one believes in it but you, your pain is madness or hysteria.”
Naomi Wolf in The Beauty Myth, “Violence” (1990).

How do we know if another person is in pain? If the person is overtly grimacing, groaning, moaning, or writhing, does that actually prove the existence of pain or even its intensity? We only know for certain through self-assessment if we are comfortable and relatively pain-free. How do we ultimately know anything clinically about our patients? We obtain a thorough history. We ask specific questions that lead us toward a set of possibilities. We formulate a working hypothesis about the origin of the pain and the perpetuating mechanisms. We perform a careful physical examination looking for signs that there is some anatomical or physiological abnormality. We test our initial hypothesis and reach a judgment about the cause and possible solutions. Finally, we propose a course of action likely to benefit our patients. These same ideas hold true for evaluating pain complaints.

If patients tell us they are hurting, how much are they? Does it do any good to challenge their reports of pain or to second-guess them? Do we expect our patients to change their pain intensity reports because we doubt their initial veracity? Do we have to believe all reports about pain intensity from all of our patients under all circumstances? We must assume that patients are generally truthful to be able to treat their pain or any other medical conditions. If we are left to doubt the truthfulness of patients seeking our assistance, how will we ever be able to relieve any painful disorders? The most probable cause of unrelieved pain and unnecessary suffering is the failure of practitioners to ask patients about their pain and to then accept and act on patients' reports of pain.⁷

Do we ever really know for certain that the pain is whatever the person says it is? We try to determine the degree of interference that the pain causes for the performance of activities of daily living. We attempt to learn from our patients by observing what activities are done more readily, more frequently, or more consistently with some mutually agreed upon change in the pain intensity. We determine the number of hours each day that our patients are out of bed engaged in activities. Rather than debate with our patients their relative pain intensities, it expedites the process if we initially accept at face value whatever our patients say about their intensities and degrees of interference until clear contradictions violate the practitioner-patient relationship. In that way, we focus on improving our patients' function, activities of daily living, and coping skills necessary for living with their chronic pain.

What do clinicians usually do when faced with patients claiming to be in pain, but looking relatively healthy? Sickle cell patients describing terrible pain (an 8 out of 10) yet watching television without overt moaning or groaning, are they really having bothersome pain? We ask lots of questions about pain. We try to see how pain intensity varies over time, and how pain intensity and characteristics vary with specific activities and movements. By doing this we ultimately challenge the reality of the pain itself. We let the patient subtly know we do not fully believe what we are being told. We often suspect that the real goal for our patients may be to obtain opioids under false circumstances. We then react by decreasing the dosages of their medications or widening the intervals between administered doses to see if our patients demonstrate more “pain behavior” in a modern day “trial by fire.” What is the real harm if we just accept the reports about the pain being very high, presumptively treat pain compassionately with analgesic medications or utilize larger dosages of analgesic medications, and our patients subsequently report their pain being better controlled, leading to more activities of daily living being performed? Have we unwittingly been duped and inadvertently contributed to the diversion of medications?

When making rounds or seeing patients in the office, do we give each of our patients the benefit of the doubt? Do we continue to compare one of our patients to another or allow our patients to have whatever levels of pain and degrees of “bothersomeness” that they report? If we do work with our patients to formulate an interdisciplinary care plan, we see better compliance, enhanced trust, and better pain control. These issues are not academic. They represent the fundamental way that pain complaints are evaluated and managed by practitioners.

GUIDELINES TO BEST MANAGE PAIN

Since 1986, the World Health Organization (WHO) has had guidelines for the management of cancer pain. Cancer pain management has not only been a high priority on an international level, but also on a national level in the United States. The Agency for Health Care Policy and Research (AHCPR) published cancer pain guidelines in 1994 utilizing many of the ideas from the WHO guidelines.⁸ These guidelines came just 2 years after the AHCPR released acute pain guidelines.⁹ The American Pain Society has issued four editions of its pain management guidelines, most recently in 1999.² The American Medical Association developed the Education for Physicians on End-of-life Care (EPEC) curriculum with a grant from the Robert Wood Johnson Foundation in 1999 to help US physicians provide better pain management and other needed services for the terminally ill.¹⁰ The Joint Commission for the Accreditation of Healthcare Organizations released new healthcare facility standards concerning pain management in 1999 that took effect on January 1, 2001.³² All of these collective guidelines, recommendations, and evolving standards of care provided for a variety of strategies to manage pain effectively. The range of options proposed acknowledged the variability among patients and the uniqueness of each of their painful conditions.

In the 1980s, the view of pain management for nonmalignant pain was based primarily upon principles of behavioral health psychology. It seemed reasonable to pain practitioners to treat chronic pain sufferers in highly structured behavioral programs, emphasizing the role of function independent of pain intensity. The paradigm addressed function by setting arbitrary quotas that had to be satisfied. Rather than negotiating each activity or medication change, patients agreed to go through systematic detoxification from their prescription medications (generally barbiturates, benzodiazepines, and opioids), offending agents (alcohol, caffeine, and nicotine), and potentially reinforcing patterns of response from family members. Using operant behavioral techniques (modifying the response patterns to emitted pain behaviors by those around the patient), patients learned to do more on their own, stopped receiving rewards for remaining disabled, and in many cases did rid themselves of medications and other substances. These programs were relatively expensive, did not always return patients to gainful employment, and left the field of pain management in a quandary. What was ultimately to be done for those patients who upon completing very thorough programs, often involving a month or more of continuous inpatient treatment, still had significant levels of pain and could not improve their function without the use an analgesic medication?

In the 1990s, the acute and post-procedural pain guidelines came from the AHCPR.⁹ These guidelines pointed out the real cost of not treating acute pain in terms of morbidity and mortality. No longer was it assumed that pain was just an aggravation. Pain was correctly viewed as a clinical problem that could kill our patients. Gone were the days where we could get away with a remark like, “Pain never killed anybody, they just wished they could die.” Instead, pain practitioners began to link pain with altered immune function, compromised pulmonary function, increased cardiovascular work, delayed return of bowel activity, increased risk of deep vein thrombosis and pulmonary embolism, and worsening of sleep with consequent anxiety and depression. For the management of acute pain, there were few concerns raised about the short-term use of opioids or the emerging pre-emptive anesthetic techniques.

In the late 1980s and early 1990s, many of the ideas for cancer pain management paralleled the acute pain management strategies. We assumed that cancer patients could not participate in the operant behavioral rehabilitation programs used for chronic non-cancer pain. We provided cancer pain sufferers with a wide range of therapeutic options, from high dose opioid analgesics to specialized anesthetic blocks. As long as the patients were determined by their physicians to be terminally ill, with less than a year of life expected, a “no holds barred” approach to controlling pain was taken. In doing so, a great many Americans died far better in the last decade than in previous modern decades. The addition of hospice end-of-life care permitted the exploration of the role of anticipatory bereavement, spiritual needs, and psychosocial support for the terminally ill and their family members. These philosophical changes did much to benefit many Americans, but never became part of the standard curriculum in American health education. In 1998, only four of 126 US medical schools offered any formal curriculum in end-of-life care during medical training.¹⁰

After years of benefiting cancer pain sufferers with the use of opioid medications, selective anesthetic blocks, and numerous behavioral interventions, these and other techniques were tried for nonmalignant pain in the mid-1990s. There was initially much concern that non-cancer patients using open-ended opioid analgesics might develop out-of-control medication abuse. Combined position statements by the American Pain Society and the American Academy of Pain Medicine in 1997, along with statements made by the Pain and Policy Studies Group at the University of Wisconsin School of Medicine, helped to rapidly move the process of utilizing opioids for non-cancer pain.³³ In 1998, the Federation of State Medical Boards of the United States released a position statement concerning the role of long-term opioids in the management of pain.³⁴ By the end of the 1990s, most of the state medical boards had developed policy statements regarding the use of long-term opioid analgesics. What was interesting about this policy shift was the adaptation of the successful cancer pain management techniques to treatment of non-cancer pain.

In the most interesting twist of borrowing technology, by the late 1990s there was recognition in the acute pain management community that ideas used to control long-standing pain for the terminally ill and those having chronic nonmalignant pain could also be effective for improving the post-operative pain period. Beyond pre-emptive analgesia and anesthetic techniques came the understanding that controlled-release opioid medications for post-operative pain might lower the overall use of medication, improve the quality of sleep, decrease the intensity of pain, lessen unpleasant side effects, and stabilize the patient for rehabilitation.¹¹

THE EVALUATION OF PAIN

Putting things together clinically is what pain management is about. Clinicians must begin each pain assessment with attention to many issues. At the very least, we need to take the time to carefully consider what could be the underlying cause for the pain. We must construct a very thorough history.¹² To do this we need to have adequate time and an environment conducive to conversation. Patients must be allowed to tell us their unique stories. Pain management is not something that just happens; it must be orchestrated.

We need to inquire about all possible initiating and perpetuating factors.¹² Has there been a recent traumatization? What was the nature of the injury? Has there been recent surgery? What complications were encountered? Reviewing the operative report may prove very enlightening. Is there some unrecognized and untreated medical condition that is perpetuating the pain process? What is the patient's overall health status? Does the patient exercise regularly? Is the patient using significant amounts of alcohol, caffeine-containing beverages, or tobacco products? What about the unauthorized use of medication from friends and family members? Is there any use of illicit substances?

What about the intensity of the pain over time? From the onset of the painful condition has the pain been getting better, worse, or staying about the same? Does the pain intensity vary over the course of the day, week, or month? What is the highest level of pain during the past day, week, or month? What is the lowest level during the same time? What predictably makes the pain worsen? What makes the pain lessen? What activities can the patient still do despite the pain? What activities have been abandoned because of pain's interference?

What medications have already been tried? Which ones were effective in any way? For those medications that seemed less than effective, was the problem really that the pain was never satisfactorily controlled or was it that the pain returned too soon after taking the medication (before the next dose was scheduled to be taken)? For patients who never got relief, perhaps their medications were ineffective or their dosages were never large enough to make any difference. For patients who had their pain return too soon, the doses may have needed to be closer together or the controlled-release medication dose may have needed to be raised.

Does the quality of the pain matter? It does if we are trying to decide if the patient has neuropathic pain (pain resulting from an abnormality of the nervous system) or nociceptive pain (pain resulting from processing by an intact nervous system). Burning, tingling, and electrical shock-like pain is more suggestive of neuropathic processes than the sharp, cutting, tearing, stabbing, and gnawing pain experienced by those with nociceptive tissue damage. If the pain is neuropathic in origin, what doses of opioid analgesics should be used? Should opioids be used at all? Must we focus our pharmaceutical attention only on the adjuvant medications (antidepressants, anticonvulsants, and antipsychotics)? Opioid analgesics may be far more useful for neuropathic pain than previously thought and should be considered for neuropathic pain, especially when caused by cancer.¹³

What about screening for depression and anxiety? Do these emotions negatively impact the experience of pain? Can we treat pain in seriously depressed or anxious patients as easily as we can in those who do not suffer from such maladies? We could spend a few minutes determining the emotional status and level of well being of our patients. What coping skills do our patients currently use to manage their pain and other problems? How have our patients handled their illnesses, stresses, and pain problems in the past? Are there previously learned skills that can be utilized now? What do we need to do to help our patients adapt and function better? Do we really know, or are we going to tell our patients to “just learn to live with the pain”?

How anxiety and depression influence pain intensity is a complicated issue. The cause and effect relationship is not clear. Some studies show a relationship and others do not. Anxiety and depression may be the consequences of unrelieved pain. However, no doubt exists that pain results in considerable distress for many patients, causing anxiety, depression, and hostility, and interfering with all domains of quality of life. When patients are anxious or depressed and in pain, the initial intervention should be aimed at reducing the pain. If anxiety and depression persist after the pain is relieved, other interventions are indicated.⁷

The role of physical and sexual abuse cannot be ignored. At the University of Michigan Multidisciplinary Pain Center, 48% of women reported a history of physical abuse or sexual abuse. These unfortunate women reported more pain, physical symptoms, anxiety, and mental health care utilization compared to women who were not abused.¹⁴

Turning to the physical examination of the patient, what does the clinician observe when entering the exam room? What body position has the patient assumed? What is their facial expression? What is observed about the use of proper body mechanics and posture? Upon examination, what body parts are instinctively “guarded”? Is the examination just problem-focused and limited to the overt area of discomfort or more general in scope to determine what else may be contributing to the total pain experience? How far are we prepared to look for a cause of the pain?

Since pain arises from abnormalities in muscle, nervous, and skeletal structures, these must be carefully examined. Starting from the head and working to the toes, check the range of motion at major joints and in the spine, determine the muscle strength for major muscle groups in the affected area, evaluate sensation for pinprick versus light touch discrimination, and compare the deep tendon reflexes from side to side. Imaging studies, electrophysiological tests, body fluid analyses, and other data may be needed to complete the examination.

MANAGING PAIN

Assuming that we have tentative explanations for the pain, what are we going to do for our patients? What can we utilize from the various proposed guidelines for the control of pain? We could start by classifying pain according to the length of time experienced.¹⁵ If only present for hours to weeks, we could utilize the acute pain management guidelines. If present for months to years, we would have to use the strategies for chronic pain management, regardless of the underlying cause.

To control acute pain, we might initially consider anti-inflammatory agents and opioid analgesics. To decrease the discomfort of any underlying inflammatory process, anti-inflammatory agents would prove very useful, whether non-steroidal or steroidal in their composition. The use of these medications would allow us to control the toxic chemical events leading to the sensitization of the nervous system and the further experience of pain in response to injury. Opioid analgesics could then be added upon this base of inflammation control to maximize comfort.

Which nonsteroidal anti-inflammatory to use is not as important as using some agent. While the toxicity profiles of the nonsteroidal anti-inflammatory agents vary from medication to medication, the ability of these agents to relieve inflammation and pain is clear. When inflammation plays a role in the development and experience of pain, relieving the inflammation is very likely to improve the pain. Unfortunately, NSAID use may lead to potentially serious complications such as bleeding, gastric ulceration, hepatic dysfunction, and renal failure.⁸

What about opioid analgesics? Should they be used for acute pain? Certainly they are used in the acute setting.² Opioid analgesics have actually become the standard of care for post-procedural pain management. Common opioid side effects, including sedation, constipation, nausea, vomiting, itching, and respiratory depression, should be anticipated and addressed early in treatment. We must be aware that optimal analgesic dosages vary widely among patients. In all age groups, there is great variability in opioid doses required to provide pain relief, even among opioid-naive patients having identical surgical lesions.² This variability supports the necessity to write analgesic orders that include provisions for supplementary doses.²

The factors that limit our use of opioid medications usually involve patient and professional barriers. Patients are concerned that they might get “hooked” on the medication, or might appear weak if they cannot handle the pain that others can. Practitioners, especially those who prescribe opioid analgesics, worry that too much medication could cause respiratory depression, that controlling the pain might mask emerging problems, or that patients might not want the side effects associated with starting opioid medications. Due to misconceptions about opioids, there is still a belief that a very narrow divide exists between the benefits and risks of prescribing opioids.⁹ There are certain patient populations that can be identified as being at higher risk of respiratory depression, including elderly or debilitated patients, following large initial doses in opioid-naive patients or when opioids are given in conjunction with other agents that depress respiration.

What opioid we often prescribe involves elements of folklore and tradition. Commonly used opioid analgesics are listed in Table 1. In my own medical training it was simple: one or two tablets of Darvocet N 100® every 4 to 6 hours for mild to moderate pain or Demerol® 50 mg to 75 mg intramuscularly every 4 hours for moderate to severe pain. Why was I taught to use Demerol®? Because it spared the Sphincter of Oddi, of course! At least that is what I thought whenever I took an examination. Today there is interest in a variety of different opioid agents. Why do we need these other medications? Meperidine has not treated our patients so well. Higher doses of meperidine have caused confusion, delirium, hallucinations, and seizures due to the accumulation of its metabolite normeperidine.² Although oral doses of meperidine are only 25% as effective as similar parenteral doses, they produce just as much of this toxic metabolite. Patients with compromised renal function are particularly at risk of having side effects due to normeperidine accumulation. Naloxone does not reverse this hyperexcitability, and may even exacerbate it. For these reasons, meperidine should not be prescribed for more than 48 hours in acute pain patients without renal or CNS disease, or at doses greater than 600 mg/24 hours, and should not be prescribed for chronic pain.²

Mixed agonist-antagonist medications like pentazocine (Talwin®), nalbuphine (Nubain®), and butorphanol (Stadol®) produce analgesia by binding to the kappa opioid receptors while antagonizing the action of traditional opioid agonists at the mu receptors.² Both the analgesic and respiratory depressant effects seen at higher doses are decreased due to their antagonistic actions. There is no compelling evidence that agonist-antagonist medications offer any advantage over the pure opioid agonists, and they should be used with caution due to their propensity to cause confusion and hallucinations.²

Neuropathic pain has been thought to be relatively less responsive to opioids than other types of pain. Methadone is believed to be a N-methyl-D-aspartate (NMDA) receptor antagonist and might be more effective in controlling neuropathic pain. Pain intensity was not different in advanced cancer patients with neuropathic pain when compared to patients with non-neuropathic pain before and after methadone administration.¹⁶

The speed of absorption is the main difference among various oral morphine preparations. The maximum plasma concentration and the time to peak are most significant. Subjects used, duration of treatment, type of preparation, doses administered, co-administration with food, and method of analysis have much to do with the substantial variability noted in medical reports. Examining 69 studies of peak plasma concentration and time to peak plasma concentration for different morphine preparations, data from healthy volunteers mirrored that seen for patients, but with less variability. There was little difference between single and multiple doses; no difference between forms of immediate-release products; and little difference between specific brands of controlled-release medications. For once-daily preparations, there were differences in absorption that were evident when comparing fed and fasted patients.¹⁷

The oral route is generally preferred for most patients. When oral analgesics cannot be tolerated or when the onset of the pain is rapid, alternative routes like parenteral, rectal, buccal, and sublingual are often considered. The sublingual route has been used successfully with fentanyl and buprenorphine products, but has not been well documented for morphine. The nonlipophilic and highly ionized properties of morphine limit its sublingual effectiveness for most patients.¹⁸

What is the right dose of analgesic medication for patients after surgery? The appropriate dose would be the amount needed to alleviate pain and not result in intolerable side effects. How is the right dose determined? Not from reading the PDR® or the package insert! The proper dose is determined by continual patient assessment and the active involvement of both the patient and the practitioner(s). The ultimate goal should be using the least amount of medication possible to keep our patients comfortable.

Patients not only require a basal level of medication but must also be provided with extra immediate-release medication to meet their moment-to-moment demands known as “breakthrough pain” or “incident pain” (transitory flares of pain). The dose of this extra medication for incident or breakthrough pain should be about 5% to 15% of the total 24-hour amount of medication and can be administered every hour if PO, every 30 minutes if SC or IM, and every 10 to 15 minutes if IV.¹⁰ Patients must be encouraged to use this extra medication if needed. There won't be just one fixed dose of medication to meet the needs of all patients.² There will be ranges of medication doses for our patients. We will need to frequently check back with the patients to obtain their degree of satisfaction. Despite all of our best intentions, only the patients know the extent of effectiveness.

Can a surgical patient go straight from the operating room to oral medication? That depends on the patient. Once patients are alert enough to swallow, oral controlled-release opioid medications like MS Contin® and OxyContin® would allow for the establishment of stable blood levels and adequate onset of analgesia. While MS Contin® might have a slower onset of analgesia, OxyContin's® analgesic effects are seen in 1 or 2 hours. With blood levels stable and no peaks or troughs to worry about over the next 8 to 12 hours (depending upon the medication selected), practitioners could make fairly accurate assessments about the need for breakthrough medication. More importantly, as reported in one study, patients taking controlled-release medications, compared with immediate-release or as needed medications, experienced a lower incidence of itching, the quality of sleep was better, the overall pain level was lower beyond 12 hours after their surgery, and global satisfaction was better.¹¹ Controlled-release opioids are now being considered by some practitioners for the control of post-procedural pain. It settles many patients' minds to know that their pain is under continuous control and that they may still have additional breakthrough medication if needed for their incident pain.

COST OF TREATING PAIN

What are the costs associated with the management of pain? It obviously depends on the type of pain experienced and the context in which pain arises. Surveying outpatients with cancer about their direct costs due to their pain-related hospitalizations, emergency room visits, physician office visits, and use of analgesic medications along with their indirect costs from money spent for pain-related transportation, complimentary methods to improve pain, educational materials, over-the-counter medications, domestic help, and childcare found that three-fourths of patients had direct pain-related costs averaging $891/month. Higher levels of pain intensity, resulting in greater interference with activities of daily living and the presence of incident pain predicted higher direct and indirect costs for medical care.⁴³

What about costs associated with newer medications compared to older medications? Cost may not be as simple as we might think. Only by knowing the total impact of pain on a larger system's budget do we really know true costs. Trying to use a less expensive “generic” medication may result in more money being spent on nursing administration time, more frequent emergency room visits, longer hospitalization, and less overall patient satisfaction leading to complaints.

In one study comparing patients taking controlled-release oxycodone to patients taking time-contingent scheduled doses of immediate-release oxycodone and as needed doses of immediate-release oxycodone, those taking the fixed-doses of immediate-release oxycodone often failed to take their medication in the manner prescribed. Some patients failed to take the medication during the night while they slept, so they awakened in pain. In addition to having improved analgesia and better sleep, patients taking controlled-release oxycodone had less sedation and postoperative vomiting. The institutional prices charged for 20 mg OxyContin® twice daily was $5.34 a day compared to immediate-release oxycodone given at a dose of 10 mg every 4 hours in generic ($5.16/day) and brand name ($8.40/day) forms. Keep in mind, these direct pharmaceutical costs did not take into account the adverse effects that uncontrolled pain might have on overall medical costs.¹¹

When considering opioids for chronic pain of non-cancer origin, many practitioners develop “cold feet.” Ytterberg et al writing about opioids for non-cancer pain concluded that the use of opioids to control chronic pain associated with musculoskeletal disorders might be controversial despite the knowledge that long-term opioid studies for the control of non-cancer pain demonstrated low risk of addiction or abuse behavior.¹⁹ During their study period of 9 months, 290 patients enrolled in the Rheumatology Clinics at the Minneapolis Veterans Affairs Medical Center received at least one opioid prescription in the previous 3 years. One hundred fifty-three of these patients used opioids for less than 3 consecutive months, and 137 used opioids for 3 consecutive months and more. Seventy percent of patients using opioids less than 3 months and 81% of the patients using opioids for 3 months or more reported that the medications helped their pain “a lot” or “some.” Crucially, there were no generalized mean dose increases in the patients taking opioids for longer than 3 months, and 78% reported that the opioid medication (codeine and oxycodone) maintained its effectiveness over time. Thirty-two patients experienced dosage increases, but only four had escalations not attributable to worsening changes in the underlying pathology or to another medical complication. This study established significant improvement in qualitative and quantitative measures of arthritis pain with opioids and refuted the past doubts/concerns about the use of opioids for the treatment of arthritic pain.¹⁹

While uncontrolled studies show that opioids could be given chronically to patients with persistent low back pain without significant abuse, addiction, or side effects, one controlled study found that pain, anxiety, depression, and irritability were lower in patients receiving opioids (morphine plus oxycodone or oxycodone) than those receiving the non-steroidal anti-inflammatory medication naproxen.²⁰ An open-label and nonrandomized study demonstrated that continuous intrathecal morphine could reduce pain and improve function on a long-term basis for patients with failed back surgery syndrome.²⁰

THE END OF LIFE AND CANCER PAIN

What can be done to make end of life more tolerable? Pain control could help, along with the management of bothersome symptoms such as dyspnea, nausea, constipation, and fatigue. In the American Medical Association's EPEC curriculum, pain management is repeatedly addressed as the means to better manage depression–one of the issues to be addressed when responding to requests for assistance with suicide–and the action taken to make the last hours of life qualitatively better and to assist in planning the overall goals of care.¹⁰

Why not focus on pain management near the end of life? Why not utilize every medication available, including opioid analgesics, to reduce or eliminate pain? Is there a runaway drug problem coming from giving prescription opioid medications to terminally ill people in pain? Why do we ever ration opioid analgesics for terminally ill patients? Perhaps the war on drugs is off target and our patients are now the unintended victims.

Does addiction directly occur as a result of using opioids for pain relief? One chart review study of nearly 12,000 hospitalized patients with supposedly no histories of drug abuse who received opioid analgesics during their hospitalizations showed that only four of them developed an addictive disorder and only one of these was defined as major.⁴⁴ Further, retrospective reviews of more than 24,000 patients who received opioids for pain relief revealed only seven as developing an addictive disorder, indicating that using opioid medications for pain relief is rarely associated with addiction development.²¹ So rare is the occurrence of iatrogenic addiction from the use of appropriately prescribed opioids to treat pain in the absence of prior drug abuse that the AHCPR guidelines defined the risk as “extremely unlikely.”^8,9

Making cancer patients comfortable is not difficult. It is more likely that cancer patients are going to eventually die from their underlying disease, not because of the analgesics we offer. Our task with palliative care is not to unnecessarily prolong life at any cost, but to improve the quality of the days remaining. We are not withdrawing all support, only changing the focus of the care provided.¹⁰ When our intent is the relief of pain and suffering, then we are justified in offering whatever amount of analgesic medications necessary to modify the pain experienced. Giving enough medication to make our patients comfortable is not considered to be passive euthanasia, but appropriate medical care. Giving enough medication to relieve pain is the physician's duty and one of the noblest acts that any physician can perform.

In caring for cancer patients, there really are no upper limits on the amount of single-entity pure opioid agonists given. We can continue to escalate the dosages of these opioid analgesics until comfort and satisfaction occur, or until our patients are limited by intolerable side effects. Our patients need to be our guides. Unlike the nonsteroidal and steroid medications that are used to control cancer-associated inflammation and have specific dose limitations due to their side-effect profiles, opioids should be uniquely adjusted based on patients' needs.²¹

INTERPATIENT VARIABILITY

Why do some patients with cancer need more medication than others to be comfortable? Just as pain intensities vary from patient to patient in response to some injury or illness, the amount of medication needed to provide cancer pain relief also varies. It means nothing that one patient requires twice as much medication as another patient with a similar cancer burden. Patients need whatever is the amount of medication necessary to control the pain associated with their cancer.

When caring for epileptics, we never hear neurologists use language to describe any of their patients as being “out of control” with their medications. If epileptics are continuing to have seizures, their medications are continuously raised until the seizures stop or the patients become intolerant to side effects. Why are these endpoints helpful? There is no economic reason to give more medication after seizures are under good control and it is bad medicine to impart undue harm to patients. The same holds true for the management of diabetes mellitus. When do we hold back insulin because patients are “overusing it” if blood glucose levels are still elevated? Do we stop treating hypertension when we get to a certain number of milligrams of a given medication or when the blood pressure is adequately controlled and the associated risks lowered? When we talk about milligrams of some controlled substance becoming grams per day we suddenly develop selective myopia. We describe our patients as being out of control because they use their medications as we told them to do.

The amount of an opioid analgesic medication needed to relieve pain is the amount that actually relieves the pain and is tolerated by the patient. That is all that matters. Having said that, we again need to consider the management of diabetes, hypertension, and coronary artery disease to have a working model for the management of cancer pain. When don't we want blood sugar or blood pressure to be normal? When don't we want blood flowing to the myocardium? When don't we want pain well controlled?

WORLD HEALTH ORGANIZATION GUIDELINES

To control cancer pain we could look to the wisdom of the World Health Organization and the Agency for Health Care Policy and Research.⁸ Start with a non-opioid medication (acetaminophen, aspirin, or an NSAID). If pain is mild (less than 4 on a 0-10 scale) to begin with, this may be all that is needed initially. Within 1 or 2 days patients will tell us if this approach is enough. If patients are still uncomfortable or their pain is moderate (4-7 on a 0-10 scale) to severe (7-10 on a 0-10 scale), then add a full agonist opioid analgesic. Why not add a pure opioid agonist in addition to the anti-inflammatory medication? Our patients are already taking an anti-inflammatory, aren't they? We do want to provide an anti-inflammatory agent. Is the acetaminophen going to help inflammation in any way? Not likely, according to its proposed mechanism of action.²

What else must be considered when prescribing opioids? Be sure to add a stimulant laxative and a stool softener when starting opioid analgesics because opioid-induced constipation occurs with all opioids, regardless of the route of administration. Constipation is the most common opioid side effect and the only one for which individuals can never develop tolerance. Thus constipation requires a preventive approach, regular assessment, and aggressive management if symptoms are reported. Fiber-containing products may not be helpful for opioid-induced constipation, and if given to patients not consuming sufficient amounts of water, may lead to worsening of the situation. Starting patients on a combination stool softener and mild peristaltic stimulant is therefore recommended.^21,35

While the reference “gold standard” for pure opioids is thought to be morphine, many other pure opioid analgesics are available. The accumulation of morphine metabolites, morphine-3-glucuronide and morphine-6-glucuronide, may lead to significant problems with long-term and high dose oral morphine, as well as in renal impairment.^1,45 We continue to look for alternatives to morphine. Although historically not thought to be a potent analgesic, oxycodone has been available without acetaminophen and aspirin for the past decade and has proven to be an excellent analgesic with an acceptable side effect profile. Oxycodone in a variety of preparations allows the continued use of the same opioid analgesic for moderate to severe pain as our patients clinically evolve over the course of their illnesses.²²

BREAKTHROUGH PAIN

Since we want around-the-clock pain relief, what options do we have? Controlled-release medication will establish a base of analgesia that can be backed up with breakthrough immediate-release forms of the same medication. There are several forms of long-acting opioids including: controlled-release morphine sulfate (Avinza®, Kadian®, MS Contin®, Oramorph SR®), controlled-release oxycodone (OxyContin®), and transdermal fentanyl (Duragesic®). All of these controlled-release opioid medications are also available in immediate-release forms to allow our patients to titrate their medication to pain relief.

What sort of breakthrough doses should we recommend for our pain patients? One approach is to start with 1/4 to 1/3 of the 12-hour controlled-release medication dose. If our patients are taking 90 mg of MS Contin® twice daily (180 mg daily) they would need 30 mg of an immediate-release formulation of morphine for their breakthrough medication. For those taking 320 mg of OxyContin® twice daily (640 mg daily) they must receive 80 mg of immediate-release OxyIR® or OxyFast®. While capsules and tablets might take an hour to fully dissolve and be absorbed, the liquid concentrates of these opioids would be available to relieve pain much more rapidly. As a rule, once patients have to take more than two rescue doses of additional medication in a 24-hour period, it is time to increase the base dose of the controlled-release medication. This technique of regulating medication allows for the rapid control of pain and provides for a strategy to keep up with the extension of the underlying disease.

ROUTES OF ADMINISTRATION

Transdermal fentanyl (Duragesic®) is a useful alternative when oral medications cannot be used due to swallowing difficulties, if patients are intolerant to other analgesics, and if the patient's pain is stabilized and frequent dose titration is not needed.²³ While fentanyl is readily absorbed through the skin, there are a few caveats to recall when selecting this “pain patch.” The transdermal delivery system only works when the patch is firmly in contact with the patient's skin. No special skin preparation other than clipping the hair and placing the patch on a flat surface area is required. If the patient is extremely cachectic, the absorption characteristic may become erratic. Diffusion principle drives the fentanyl into the body from a rate-controlling release membrane. When the temperature is not normal, delivery is altered. During episodes of fever (temperature >104°F) or exposure to direct external temperature sources (heating pads, heated water beds, electric blankets, and car seats in the summer), the dose delivered may exceed the dose printed on the patch and lead to potential increases in serum fentanyl levels.²⁴ Duragesic's® onset of action is about 12-24 hours after the initial application and steady state is achieved after several sequential applications (in about 5 days). The American Pain Society guidelines recommend that patients are first titrated to pain relief with short-acting opioids before being switched to transdermal fentanyl.²

Notice that throughout this discussion milligrams and grams no longer matter. We continue to increase the opioid analgesic medication dose higher until patients are comfortable or limited by toxicity. If higher doses produce excessive sedation, then we can reduce the overall dosage, rotate to a different opioid analgesic, or add a stimulant medication like dextroamphetamine (Dexedrine®) or methylphenidate (Ritalin®). We could even add adjuvant medications such as antidepressants, anticonvulsants, anxiolytics, and antipsychotics to modify the pain experience and “buy back” some of the opioid dose being given.

Our goal with adjuvant medication is to modify neurotransmitter activity that is thought to participate in the processing of pain within the nervous system. The dosages for these adjuvant medications for pain management are usually lower than the dosages used to treat major depression, psychotic illnesses, and significant anxiety disorders. Interestingly, the dosages of the anticonvulsants for pain relief approximates the dosages used for the treatment of seizure disorders.

OPIOIDS AND REGULATORY BODIES

Our misunderstanding about addiction fueled by our fears of regulatory action bodies causes many patients to remain in pain unnecessarily. One retrospective survey conducted by Joranson et al evaluated trends in the medical use and abuse of opioid analgesics. Between 1990 and 1996, there were increases in medicinal use of fentanyl (1168%), morphine (59%), oxycodone (23%), and hydromorphone (19%) with a decrease in meperidine (35%). Between those same years, the proportion of mentions for opioid abuse relative to total drug abuse mentions to the Drug Abuse Warning Network decreased from 5.1% to 3.8%. Specifically, reports of abuse decreased for fentanyl (59%), meperidine (39%), oxycodone (29%), and hydromorphone (15%), with only a slight increase for morphine (3%). Despite the increasing medicinal use of opioids to control pain, there was no contribution to opioid abuse during the time period studied.²⁵

More recently the abuse of prescription opioid analgesics has made national headlines and has served as grist for all of the major networks, news magazines, major newspapers and congressional hearings. This has been very unfortunate for the field of pain management and has reopened the same confusing dialogue about the role of opioids for chronic non-cancer pain that we had in the past. The tragic abuse of opioids, most notably OxyContin®, now makes many practitioners think twice about wanting to even care for patients suffering with pain. While the number of abusers who have come to harm or died from their misuse of opioids is fortunately limited, it has not been insignificant. Trying to better understand this new abuse of prescription opioids has not been easy for pain practitioners who worry that they too may become targets for deception by unscrupulous individuals impersonating patients with pain. The most recent Drug Abuse Warning Network data through 2001 has sadly demonstrated that some Americans are quite willing to die to get high. Emergency room mentions for fentanyl, hydrocodone, hydromorphone, morphine, methadone, and oxycodone have all increased over the past few years (Table 2)³⁸.

Many physicians believe that they risk disciplinary action if they use high doses of opioid analgesics or other controlled substances to manage pain. They also believe that if they under-treat pain, they risk no professional consequences. Patients have the right to adequate pain management. In the past, physicians might have successfully defended a stance of withholding medication by asserting that there was no medical consensus about how to provide adequate pain care. With the emergence of national, state, and medical board guidelines concerning the relief of pain, this is no longer a viable strategy. There is now a developing consensus that not properly managing the pain of our patients is a legal and ethical failure, not just a clinical failure.⁴⁶ It is only a matter of time until patients with inadequate pain control look for more professional accountability and initiate complaints against their practitioners leading to disciplinary actions by medical boards.²⁶ Already, some physicians (in CA and OR) have been disciplined by their medical boards for the undertreatment of pain.

It has actually been found that less than 5% of the disciplinary actions taken for over-prescribing opioids by state medical boards in any given year directly concern the treatment of chronic pain.²⁷ While even though 33 states have enacted intractable pain treatment acts between 1988 and 1997, and many medical boards have adopted their own administrative rules and/or established guidelines for opioid analgesics in the treatment of chronic pain, physicians still fear the threat of regulatory action. This may be due to the perception that there is some risk of being disciplined by a state medical board for over-prescribing and no risk at all for under-prescribing. In 1997, Kirk Robinson and Kathryn Tucker, representatives of the organization of Compassion in Dying, sent a memorandum to all medical boards in the United States that argued receiving adequate pain medication was a right accorded to dying patients. Additionally, Compassion in Dying gave notice of its willingness to assist chronic pain patients and their families in making complaints and/or in filing suits against practitioners who under-prescribe rather than provide adequate pain relief.²⁷ This organization's involvement lead to the successful lawsuit against a CA physician for the undertreatment of pain in one of his terminally patients.

In trying to stay clear of the regulators, the careful physician must be prepared to prescribe opioid analgesics using a consistent methodology. I proposed such a schema in 1998 and again revised this in 2002. “Ten Tips” for prescribing opioids includes:

• Obtain a thorough history and perform a first-rate physical examination;
  
• Chart everything you see, think, feel, and hear about the patient;
  
• Obtain informed consent for long-term opioid therapy;
  
• Obtain a second opinion from a colleague to verify the plan of care if you are not a pain practitioner;
  
• Get the patient to agree to use only one pharmacy and to obtain opioids only from you;
  
• See the patient regularly (at least every 30 to 90 days);
  
• Prescribe controlled-release medications to stabilize the blood levels to limit the “buzz” associated with immediate-release medications;
  
• Keep the dosages controlled to the amount necessary to provide comfort;
  
• Check the urine drug screen (understanding the methodological limits of the test being used) to make certain what you are prescribing is being taken and that illicit substances are not being used; and
  
• Obtain additional education related to the current practices of pain management and the use of opioid analgesics.^28,39
  

It is less likely that practitioners would ever be accused of improper behavior if all of these steps were routinely followed.

MANAGING PAIN AND MANAGING CARE

The introduction of managed care has led to the end of lengthy behaviorally oriented pain management programs. There has also been a shift to outpatient services unless there is a clear need for some technology only available in a hospital environment. The boundary between hospital and home-based care has become more blurred every day as we send more seriously ill patients home with visiting nurses, durable medical equipment, hospice support, and everything else we can imagine. How long will it be before coronary artery bypass patients will be sent home from the operating room with a lightweight portable ventilator and a syringe to deflate the cuff on their endotracheal tubes when they are ready to remove their own tubes? Other than a few “technical problems” to be resolved relating to managing one's own cardiovascular stability, pain management may be the single best reason to want to stay in the hospital after coronary bypass surgery.

It is our obligation to do a better job at managing pain in America. We must get past the barriers that prevent us from really making patients comfortable. We should educate our patients and their families to request adequate pain management services, to utilize these techniques and services without fear, shame, or guilt, and work with health care educators and policy makers to provide regulatory relief.

The Joint Commission for the Accreditation of Healthcare Organizations now demands that we establish prospectively developed policies and procedures regarding pain assessment and education for patients and their family members, provide pain relieving treatments, and measure outcomes starting in 2001.³² The Centers for Medicare & Medicaid Services plan to use the annual Medicare survey process in California to ensure compliance under the Patient Self-Determination Act of 1990 with the 1997 California Pain Patients Bill of Rights.³⁶ The State of Nevada amended the Physician Practice Act on March 15, 1999, to make pain management the duty of Nevada physicians.³⁷ State medical boards will increasingly have to take action against professionals who can't or won't manage pain. Failure to relieve pain will eventually jeopardize professional licensure, impugn reputations, and cause litigation.

ARE YOU A PART OF THE PROBLEM OR A PART OF THE SOLUTION?

It is unfortunate that too few of us actually learned how to manage pain, even though care has become “managed.” We were not taught how to manage pain in our professional schools. We were given “one size fits all” strategies for pain management. These simple rules that supposedly made most patients comfortable most of the time also led patients to believe that they were “good patients” if they never touched the call bell, if they never complained, of if they never challenged our “expertise,” and ultimately these patients were forced to live with their pain. Our response to pain patients was predictable and patterned: “You'd better not take too much of this stuff, or you might get into trouble,” “I'm sorry but I can't give you any more of this, you're already at the limit,” and “What's wrong with you? You're taking too much of this.” At no time did most of us realize that receiving optimal pain management was the most appreciated experience by our patients. We could make our patients very comfortable as the rule, if we just had the will to do so.

We have to get past our “two-step goose-step” to use the complexity and talents of the mind and nervous system to relieve pain. If you believe that the relief of pain and suffering is the highest purpose of a healthcare practitioner, bless you. If you still believe that pain medications must be used with extreme caution and as infrequently as possible, consider yourself to be on notice. Pain management may become a new, potentially lucrative area of tort law.²⁹ Nurses and physicians should expect to be liable for the undertreatment of pain.³⁰ At the very least we must be prepared for civil negligence litigation or medical disciplinary action, not to just enrich lawyers, but to promote increased attention by physicians who are providing adequate care to patients in pain.³¹ The recent adverse ruling and monetary judgment against Dr. Wing Chin in CA for the undertreatment of William Bergman's cancer-related pain should now be our call to arms in the fight against unnecessary pain and suffering.^{40, 41}

Chronic pain remains too common and costs our society directly for the health care services provided, for the welfare and disability payments made to sufferers, for the lost tax revenue and lost productivity. Despite all of the progress made managing pain over the past 25 years, pain is still a tremendous burden for too many people.⁴² It is now the responsibility of all practitioners to do something about pain and to move past simple cost-benefit analyses to recapture the soul of healthcare. Every practitioner must make a commitment to relieve pain. How we treat pain and the people who suffer with it today is the best predictor of how we may one day be treated in our own future. Doing more to relieve pain now will make our own lives more comfortable in the years ahead.

 REFERENCES 

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