In this section, I want to talk with you about the core concepts of chronic pain and how to use opioids in its management. To be prepared to adequately address the clinical area, clinicians need two overlapping sets of knowledge and skills, how to identify and manage particular pain syndromes, and how to, if needed, safely use opioids as a tool in their management. This seminar focuses primarily on the second of these domains. A detailed presentation on even the most common pain syndromes is obviously far beyond the scope of time available. However, it will be useful to spend at least some time talking about the nature of chronic pain, how it is different from most acute pain, and the role opioids may play in its management, including their potential utility as well as limitations. We all hear about acute and chronic pain, but what do we mean by these terms? Acute is usually pain that is from an obvious source, resolves as the tissue damage resolves, and is seen as protective in function. Chronic pain, however, on the other hand, is pain that has been present for at least three months, does not necessarily correlate with tissue damage, has lasted longer than clinically expected, and eventually really has no protective function. How, why, and in whom acute pain transitions into chronic pain is under very intense study with many opinions as to the mechanism for these transitions. At this point, it looks like a variety of neuroimmune modulations acting both in peripheral and centrally areas lead to the chronic pain transition. What is well known is that once a transition to chronic pain has occurred, then the ongoing pain is reinforced as a disease unto itself. This is a central concept today, that pain becomes a disease unto itself. It does not depend on continued tissue damage. It is self-supporting and progressive. Truthfully, I think this is one of the most important charts in this training. It is simple, direct, and obvious in how it outlines why pain is so difficult to treat, why some of the patients are so difficult to contain, and why the culture at large, and medicine in specific, are finding pain management such a hot button. On the left, we see the cost associated with pain, at least $650 billion a year. As we move into new models of care, soon to be mostly population-based, we need to optimize pain management for cost containment and better outcomes. When we realize pain is more prevalent and costly than heart disease, cancer, stroke, and diabetes combined, then we begin to realize how important it is to treat in a proactive and systematic way. For the patients that we see daily, impact of this disease in the blue bubbles towards the bottom of the slide, this is a disease that disrupts every moment of the day. Chronic pain is actually felt constantly, unlike any other disease. Heart disease, diabetes, even cancer are not impinging on your every move, nor felt so intrusively and persistently. Pain is a constant, averse reminder that never turns itself off, constantly limiting most everything a patient does every moment they are awake. This supports the formation and progression of the more psychiatric elements seen in the yellow towards the upper right. Depression, anxiety, sleep disturbance, these are present in the majority of pain patients, compounding the impact of pain as a disease. These become independent risk factors related to the severity and outcomes in chronic pain. As can be seen intuitively, all these factors feed back into the complex whole. Not treating them in unison leads to poor resolution of chronic pain as a disease. Treating all of these elements makes treatment of chronic pain highly challenging, yet incredibly rewarding when successful. How we treat this population is becoming more important, not just due to the concern for bad outcomes in the 15,000 people dying every year from prescription drugs, but also due to the magnitude of the pain population and the cost. As the healthcare system changes in the next few years, we will have to manage this pain population with a chronic care model. Instead of a fee-for-service approach, we will be incentivized to use a population approach. This will require clinical information systems that can identify patients with chronic diseases and track the care through a complex and, at time, intensive treatment. Access to competent patient care simplifies and optimizes decision making. This access to information permits formation of an efficient health delivery system and identification of chronic pain patients as a group will permit clarification of the most common difficulties and potential services in the community. This will permit the organization of community services that can actually fit these needs. On the level of the individual and the clinical team, this disease awareness and preparedness will lead to improved outcomes, clinically and financially. We will have to see chronic disease as entities that need an organized and reproducible team approach to have optimal outcomes in populations. I will be approaching pain as a biopsychosocial event, so let's start with the biological. I want to spend a few minutes talking about the different types of chronic pain. My purpose is to take this enormous topic and make it simpler and more manageable, clinically, by breaking it down into smaller pieces. Clarifying some of the subtypes makes the whole more understandable and eventually more approachable in terms of what to do for treatment. With this hope for simplicity in mind, let's just look at these questions. Is all chronic pain the same? Is it all equal? Is it right to talk in general terms about treating chronic pain? Are there different types of chronic pain? This image is a bit busy, but it nicely pulls apart the different categories of chronic pain. First, nociceptive pain, seen on the left, is the classic pain we all understand from our experiences on a daily basis. This is the pain that comes from tissue damage of some type. In nociceptive pain, the nervous system is intact, doing what it is supposed to do and nothing more. It is clearly protective in function, helping us stay safe and informed about our surroundings. This is the most common type of acute pain, and nociceptive pain also occurs most commonly in chronic pain. It is still the system at work in rheumatoid or osteoarthritis and many other chronic pain conditions. It is commonly the largest contributor to chronic pain of the low back. It is also involved in most chronic pain conditions in general. The quality of this pain is commonly aching or throbbing. It can be sharp at times. Neuropathic pain is pain caused by damage to or dysfunction of the nervous system. This is most commonly seen in post-herpetic neuralgia, diabetic peripheral neuropathic pain, and other chronic conditions such as HIV, post-stroke pain, spinal cord injury, phantom limb pain, complex regional pain syndrome, even chemotherapy-induced pain. This pain is harder to localize and tends to be more burning or electrical. It also has the capacity to show up as allodynia. Allodynia is the presence of severe pain caused by a non-painful stimuli, such as pain felt just by touching the skin of a complex regional pain syndrome patient. Sensory hypersensitivity is the pain of the nervous system that has become sensitized to pain inputs. This is at times referred to as wind-up or central sensitization. This type of pain usually follows chronic pain inputs that, due to neuroplasticity, transform and enhance CNS neurochemical response to pain. This neuroplastic change, commonly neurochemical, but at times can even be anatomic. This type of process, in particular, is why pain becomes a disease. So what is central sensitization? As noted briefly in the last slide, this is a very important pain entity, the central reason for pain becoming a disease into itself. There is substantial research in animals and humans that document the neurophysiologic changes occurring due to chronic pain inputs. We've all heard about neuroplasticity, the capacity for the brain to continue to change in response to the environment. Pain is a hallmark disease model for neuroplasticity with a large number of changes in both the spinal cord and the brain that occur with ongoing pain inputs. Research indicates that the spinal cord and brain both adapt. In the spinal cord, there are cells between the first and second order neuron called wide dynamic range neurons. These are part of a pain modulating system. Following chronic pain inputs, they actually begin to enhance the reception and transmission of pain to the brain. In addition, there are changes in the opioid receptors and the glial cell function at the cord level. In the brain, there are so many sites of potential sensitization that it would take days of lectures to present. These changes are too numerous to discuss, but involve changes in glial cell function, in MDA receptor function, opioid receptors, and many more. These changes can lead to independent pain in diseases such as fibromyalgia, complex regional pain syndrome, interstitial cystitis, irritable bowel, and others of which I'm sure you've heard of. We also know that stress increases the release of activating neuromodulators, and these themselves interact with the central sensitization system to further enhance pain levels. These stressors can be emotional or physical, and this leads to clinical confusion. The practitioner can be left with the feeling that the stressors are the cause of the pain, rather than a factor that stimulates the response to the pain. Treating the stressors then will improve pain response, though the stressor itself is not the central etiology of the pain. One of the other confusing aspects of central sensitization is that it is co-occurring with other chronic pain conditions. It becomes a part of the pain picture of other more mechanical pain generators. I like this Venn diagram because it represents more accurately the three types of pain and how they relate clinically. It is believed that many patients with chronic pain have more than one type of pathophysiology contributing to their pain. Even though we can identify a pain pathology as having a primary physiologic pain type, there is commonly overlap with other pain physiologies. These are not just comorbid pain conditions like low back pain and fibromyalgia, but syndromes that are causative of each other, like spinal pain with a radiculopathy. The most underdiagnosed and hard to determine is a level of hypersensitivity that is contributing to a chronic pain of another type. How much of low back pain, for instance, is driven by central sensitization? This could rise to the level of fibromyalgia and full body pain following the onset of a back pain condition, or just augment the low back pain itself due to increased pain reception at the primary low back pain site. I believe these mixed pain states are very common as clinicians. We need to consider them when we are confused about the level of pain reported by the individuals. Now that we have briefly covered the biology of pain, let's take a look at the psychology of pain. We will take some time and look at the contribution of mood disorders, the complication of personality disorders, and the reality of the substance use disorders in addition. As you can see, depression occurs at a predictable rate in humans. This applies to all cultures at about the same rate, though there is a gender bias of women having higher rates diagnosed than men. In the U.S., the depression rate is about 5% currently, 7-10% yearly, 17-20% lifetime. In pain patients, though, the depression rate is 30-54% currently, up to 65% lifetime, and for low back pain, up to 80% lifetime, sometimes for upper extremity pain. This can include increased suicidal thought, with rates are up to three-fold greater than average population. Obviously, this is a substantial increase. This is likely due not only to the constant pain limitations and the loss of social function that may well be partially a neurochemical process in addition. Anxiety is also substantially increased in the pain-free U.S. population. There's a rate of 10.6 to 13.3 for yearly. In pain patients, overall prevalence is 16-50%. This contributes to the difficulties in pain coping, catastrophizing, sleep disturbance, irritability, and enhances pain responses in some individuals due to catecholamine activation of the CNS. As we all know, personality disorders certainly occur in chronic pain. The compositive studies indicates that 31, maybe even up to 81% of patients with pain may well have personality disorders. This is higher than the average population, but there's some contention about these numbers and how much that they actually may differ from most other standard medical clinics. Historically, there has been a kind of medical lore that assumes some types of personalities would be more likely to develop chronic pain. For instance, borderline personality or histrionic personality might be more prone. Interestingly, that has not been supported by the majority of the literature. There is no pain-prone patient. There is actually a nonspecific relationship between personality, psychological problems, and pain and its ability to predict who will become a chronic pain patient. It appears that the majority of psychopathology actually appears to develop after the pain condition. There is even some evidence that personality, which is not supposed to change, may actually improve following more optimal management of the pain. Newer evidence in 2017 suggests that there may be a cohort that they call global symptom cluster that may have some predictive quality for quantification of pain, but more research is needed. In the current environment of pain management, the issue of substance abuse has become large. Epidemiology indicates that the rate of substance abuse in the population has a total lifetime prevalence of 16.7% with alcohol at 13.5%. Another drug use, illicit drug use, at 7%. In pain patients, recent meta-analysis indicates illicit substance use at 8 to 12% in the pain clinics. Of additional interest is the rate of comorbid pain in opioid addiction is 29 to 60%. I think it's important to remember this point when in the clinic, that pain patients have some slight increase in substance use rate, but not dramatically so, unlike what we fear or are led to believe culturally. The social element of the disease of pain is just as extensive and complicated as the biological and psychiatric. For years, we did not recognize the impact of pain in the culture. Part of this likely arose from not having good options for pain control, even in surgery. We were left with alcohol, distraction, and a bite block. We did slowly advance our options, but our belief tended to move more slowly. This is seen in things like our assumptions historically that babies did not feel pain during procedures. We certainly progressed and in the 80s and 90s started recognizing the need for a more compassionate view of pain. This led to changes such as pain is the fifth vital sign and increased use of opioids for chronic pain control. As a treatment of pain was more culturally supported for the use of opiates, they increased and the death rate started to climb. What has followed is old news now. The death rate climbed precipitously, heroin use exploded, and then fentanyl came in for the final punch, with nearly 60,000 opioid deaths a year over the last few years. This death rate is the face of the opioid crisis, and the response has been substantial within institutions, states, the federal legislative groups, and the North Carolina Medical Board all working towards a solution. New guidelines like CME requirements, STOP Act, SOPI, CSRS screening, and institutional changes have all worked towards managing the impact of opioids in our communities. The addiction community has stepped up outreach and treatment in addition. The losses in our communities have been catastrophic and will not be forgotten. There has also been collateral damage that is difficult to address due to the passionate reactions related to the opioid crisis, and that is the drop in the access to pain management. This presents its own dangers, unnecessary death included, and as a pain practitioner, I've been compelled to assess my role in these crises. I live in both of these dangerous worlds, too many opioids and also too little pain management for broken and suicidal individuals. I've spent a substantial amount of time trying to sort out the different elements so as to find the optimal middle path. To sort this out, I will start by using this slide. This shows the three stages of the opioid crisis, starting with the increase in opioid prescription writing. This is clearly physician-related and was in response to pain as the fifth vital sign. This arose from the understanding pain was undertreated along with mistaken belief that opioids for pain had low addiction-generating potential. Interestingly, prescription writing peaked in 2012 and has since dropped 33%, not its lowest rate in 13 years, but notice that the death rate has continued to climb. The second and third waves of the opioid crisis have been the deadliest and directly related to significant increases in heroin and fentanyl deaths, the latter keeping us at very high rates to this day. The intuitive assumption is that this must be addicts that are dying. However, when looking at the rate of opioid or heroin use disorder, we find that the rates increase somewhat but not nearly as much as the death rate. Opioid use disorder rates have been dropping for four to five years, but the death rate continued to climb and continues to linger at these higher rates. As noted previously, the rate of substance use disorder in pain clinics is eight to twelve percent and the normal background rate is seven to eight percent, again not a dramatic difference. So what is my point? Why am I appearing to minimize in some ways this horrible wave of death from the opioid crisis? My concern is that as humans, we make assumptions constantly that are commonly based on incomplete or sensational or fear-inducing information. When this happens, unintended consequences occur that can have just as devastating an outcome as those we were trying to manage initially. I fear that currently increasing rate of depression and suicide across all age groups and suicide appears to be threefold higher in pain patients. Pain management has contracted substantially in the last four years, with over 25 to 30 percent of primary care practitioners in North Carolina refusing to treat pain of any type. I want us to be very careful in prescribing opioids, taking all the precautions we can, keeping the doses as low as possible and using safer meds, but remember that pain management is not feeding an out-of-control mass of addicts that are dying due to exposure to opioids. It is not an accurate assessment and if it is believed, it just increases our risks in other ways that are parallel. So who is dying? About 15 to 16 thousand are dying from prescription medications each year and half of them were not seen by an MD. Getting those medications, about 65 percent, from friend, neighbor or relative. The rest are overdosing on illicit opioids substantially due to the increase and variability of the heroin potency along with the presence of fentanyl. Illicit opioids are vastly more potent than they were before 2009, driven by changes in production. The level of addiction has not increased substantially as commonly assumed. The data does not support this belief, but that belief infuses the decisions of practitioners and legislators and the general public and unintentionally increases other life-threatening risks. How does this impact you in your clinic? Avoid the assumption that all opioids lead to addiction, that pain patients are commonly addicts, that the best option is not treating pain at all due to the hassle and risk. Pain has an enormous presence in our world and will not be avoided without consequences. Now that we have seen the biopsychosocial sides of pain, how do we approach treating them? First of all, treat the biological. We can approach the pain generator, the primary lesion, with surgery or their interventional procedures such as epidurals or facet injections. We can target the pain symptoms alone with pharmacology or interventional tools. We can try to rehabilitate with physical therapy through exercise, massage, gait and posture training or thermal therapies. Complementary treatments are popular and effective, employing yoga, guided imagery, acupuncture, etc. The psychological needs can be addressed through therapies employing cognitive behavioral therapy, biofeedback, relaxation, problem-solving, addiction treatment, guided imagery, hypnosis, there's many. The patient can work with self-management techniques like pacing, activity, planned rest, etc. The social elements may be accessed through risk assessment, social support, collateral data, treatment protocols, NCS, CSRS and naloxone kits. We have seen the outline of the disease of pain and the treatment of all the components. We'll be hearing more about many of these in later modules in more detail. For a moment, I want to suggest an approach to the patient sitting in your room. How do you work with potentially difficult patients using potentially dangerous medications? We know that patients worry that we will not believe them when they discuss their pain or that we will not understand when they use their meds too quickly during a pain flare or fear we will judge them because they are not functioning like the rest of society. They fear exposing their mistakes, their hidden behaviors and parts of their personalities that make their life difficult. This is natural human behavior that we would all display in similar situations. The problem is that as a practitioners form the perception that the patient may be hiding something or that the patient shows any concern about their own behavior, then the practitioner gets anxious, worried, self-protective. When we add dangerous medications and the fear of legal consequences to the mix, then the wattage of this fear within the practitioner gets even higher. If we as practitioners then come from a place of catching them in these normal behaviors, we risk setting up a dynamic that is counterproductive to our own intentions. If we take on the role of playing gotcha, they will naturally, just as we would in that same situation, take the role of hiding. In addition, if your task is to catch them at something, then you are done with your assigned task once you have caught them. You are not clinically treating them, you're just catching them. Commonly the treatment then stops after the catch. At that point the patient loses, it can feel like you win, but there's no treatment after the catch and the situation starts again somewhere else after you kick the patient out or they leave or worse yet turn to illicit opioids for pain control. In the coming population care environments where we will be responsible for groups of people, this will be a small catastrophe since a patient will not be able to be discharged from your groups. You're still going to be responsible for the patient and the bottom line. Quickly discharging these patients has become a workable and in some ways appropriate approach to the patients in a fee-for-service world, but in the likely future of population care we have to find a different way out of this conundrum. I suggest a different approach, which some of you may already apply. I suggest that as much as possible we practice an approach that is curious but not right. In general, it is easy to be right. Being right just simply requires ignoring the input from other people, other inconvenient facts, other viewpoints, and that you can win by just getting louder and larger. It is much harder to be curious, to ask more questions, to actually ask to be taught something you may not know or fully understand. This encourages a patient to have a response less about hiding and more about educating the practitioner sitting in front of them that appears to be curious. It naturally opens the channel with the patient that we need access to so that we can get the information required for us to make an optimal medical decision. What may be surprising to some is that I'm not suggesting you become touchy-feely. I'm not asking you to just understand everybody, be a bleeding heart or a full-time patient advocate. My purpose is to help you find a way to get the information you need to prepare the safest optimal course of treatment in what is usually a very complex case. I'm suggesting this approach is a way to be tactical. The sole purpose of this is to optimize treatment and improve the patient's long-term function. Another element of an optimized approach is to share control with the patient. This is derived from an axiom I picked up which says the best way to gain power is to give it away. Consider sharing control and power. If the dynamic is to keep power for yourself and then the other person in the relationship will tend to fight you as to retain some of that power. This is normal human tendency. This fight and natural type of human aggression can be passive or active, both of which can show up in surprising ways. The final leg of this approach is to have clear limits with plenty of warning about when they're pushing too far. I use a football field metaphor that goes like this when talking to my patients. I want you to have some control in here. I want to metaphorically make you a football field to play on. I will send you fresh players. I'll suggest some calls to make. I'll help you keep your players healthy. You will essentially own the field, but I will own the walls. When you are approaching my walls, I will blow the whistle. It will not be a surprise. I won't suddenly tell you that you have gone too far. I will blow the whistle a number of times to warn you, but if you hit the wall and fall down bleeding, I will not come to your rescue. I will not let the wall break, and this is not meant to be mean. This is to keep you safe and help your long-term function. Once this is stated, then it is up to the practitioner to ensure that it's actually true, that the limits stay clear and strong. I would now like to talk about opioids and their effectiveness in chronic pain. One of the issues related to opioids and chronic non-cancer pain is that the data is not very robust in support of opioids. Most articles are literature surveys and uncontrolled case series. The limited number of randomized controls tends to be of short duration with a few up to 24 months. The sample sizes tend to be less than 300 patients and many are pharmaceutical companies sponsored. The responses tend to be limited with pain relief being modest. Some studies are statistically significant. Others can trend towards some benefit. A recent Cochrane review discusses issues related to side effects that can be substantial versus placebo and high rates of cessation, complete lack of any research on high-dose opioids over 200 mg of morphine, and lack of benefit greater than NSAIDs, right? One point of interest is that the pain literature is not substantially different than the cancer pain literature. A recent Cochrane study of opioids and cancer pain showed low quality and minimal evidence for efficacy in cancer pain. Some of the recent studies still cite a Cochrane review from 2010 that discussed opioid efficacy most directly. This was called long-term opioid management for chronic non-cancer pain. That review indicated that there are 44% of the patients showing at least 50% pain relief. This review highlighted that a common problem across most studies is that functional endpoints are few, thus improvement not well demonstrated. The fairly well balanced conclusion reads many patients discontinue long-term opioid therapy, especially oral opioids, due to adverse events or insufficient pain relief. However, weak evidence suggests that patients who are able to continue opioids long-term experience clinically significant pain relief. Whether quality of life or function improves is inconclusive. Many minor adverse events, like nausea, headache, occurred, but serious adverse events, including iatrogenic opioid addiction, were rare. This is not a clear directive, most strongly saying that we don't yet have the data that answers that question about opioids clearly. My concern is that with the opioid crisis, the opioids storyline has been disingenuously skewed. It is true that there is no good evidence for long-term benefit of opioids in pain, but the deeper truth is that there's no good evidence either way. There's just no good evidence available at all, and this includes cancer pain. Oddly, it also includes the lack of long-term evidence for efficacy of every pain treatment available pharmacologically, including anticonvulsants, NSAIDs, etc. I find myself still agreeing with an assessment by Portnoy in 2014, stating although the data are mixed, the systemic reviews generally support the efficacy of opioid therapy for a period of months and suggest that a subpopulation can benefit from long-term treatment, but there's no high-quality evidence about long-term effectiveness. And also, in the absence of adequate evidence, it is wrong to conclude that opioid drugs lack long-term effectiveness. Risks exceed benefits overall in some subpopulations. An alternative conclusion is that some patients benefit, some are harmed. Some subpopulations may be overtreated, and some are undertreated. We are left with knowing that we can't yet know. We have to use our best clinical judgment, make sure about the diagnosis, take an extensive history, start with the least risky intervention, and move up the treatment ladder. As we ascend, we recheck our thinking with newly collected data, make sure that excessive side effects, abuse, or addiction are not occurring, and follow function as the marker for success. You will hear about this in a number of ways and examples. What does this mean for a practicing clinician when considering opioid management? Starting opioids is a trial. Pain treatment does not equal opioids. Opioids are not equally effective for all chronic pain patients. Opioids may be useful in some cases, but are rarely sufficient. The goal is functional, and the function has to improve, and the management of pain is just management, not elimination. Opioids have significant risk, like impairment, dependence, overdose. Therefore, continuing opioid treatment depends on a number of things. Demonstrated efficacy, like improved function and pain management, and demonstrated safety. No aberrant medication behaviors. From here, we will move to a clinical role play on exploring treatment options that will highlight some of the elements we discussed above. Alicia, you came in for help with treating your knee pain, and we've done an evaluation, and I think we have some ideas of things that are contributing to your knee pain, so I think it's time for us to talk about some treatment options. Did you have an idea of what you thought you needed in terms of your knee pain? Yeah, so my last doctor didn't give me any oxycodone, and I never got out of pain the entire time I saw him, so I really think I need to get back on the oxy that I was on before. So you did get relief from the oxycodone? Yes, I did. Okay, well we'll keep that in mind, because I think it may be that that oxycodone will be one of the things we end up using, or something similar to that, an opiate analgesic. But you know, in looking at your record and talking with you about your record, there's some things for your particular kind of pain that really haven't been tried, so I think there's some other treatments that we want to try to make sure that we're doing the right treatment for your particular pain. And I think we'll start out with those, and we'll kind of hold the oxycodone in reserve for the time being. What do you think? I mean, I really think I'm gonna need the oxy somewhere in there. Mm-hmm, and again, you might. I'm not ruling that out at all. But you know, I have to take into consideration that opiates have limited evidence in terms of their use for the long term. We're not really clear that they work well for the kind of chronic pain that you've got. They have some risks associated with them, dependence, overdose, that sort of thing. They tend to work best when used with other treatment modalities anyway, so I think we're gonna want to use a multimodal approach anyway. Okay, so that's what I think makes the most sense. Can you live with that, or go along with that? Yeah, I guess I can. Okay, all right. Well, let's talk about some of the specifics, and we'll get started. Okay. Thank you for your attention, and I hope this has been helpful.

chronic pain

opioids

pain management

acute pain

neuroimmune modulations

psychological issues

patient-centered approach