Hello, welcome to the next lecture as part of the PCSSO core pain curriculum training. This lecture is entitled Understanding and Assessing Opioid Use Disorder in Patients with Chronic Pain. Our objectives today are to describe a neurobiological framework explanatory model for patients with chronic pain and opioid use disorder, recognize that differentiating opioid use disorder from pain is a complex task, identify key features of opioid use disorder, and describe how to perform an opioid use disorder evaluation in primary care. Let's start with a case. This is a 35-year-old female with chronic daily migraine and diffuse myofascial pain who's been prescribed opioids for five years after the birth of her daughter. The patient has severe depression and anxiety, chronic nausea, history of adverse childhood experience, neglect as a child, and obesity. She's a stay-at-home mother for two children but frequently has to put the children in daycare because she cannot care for them when she has a severe migraine. She's also prescribed chronic high-dose benzodiazepines by her psychiatrist. The patient has a history of losing her opioid prescriptions, obtaining opioids from other providers, being allergic to most other pain medication options that are non-opioid, missing appointments, and frequently asking for opioid dose increases. The questions that I want you to think about for that particular case are, does this patient have pain? Does this patient have an opioid use disorder? What factors place this patient at risk for an opioid use disorder? And what can you do to help this patient? We're going to talk about the biological underpinnings of many of these questions, and hopefully at the end of this lecture, you'll be able to answer these questions. So whatever its cause, when pain persists, it often causes secondary problems that can in turn facilitate distress and pain. So persistent pain, we know, causes sleep disturbances, other secondary problems such as obesity, anxiety, depression, PTSD. You can get cognitive distortions, increased stresses. All of these can lead to functional disabilities. So these are many of the things that are a part of a persistent pain process. Substance use or misuse can be another part of that process in patients who are at risk. As a chronic condition, opioid use disorder shares similar challenges as persistent pain. It causes many of the same issues that we just mentioned. And all of these can actually potentiate the use disorder itself. So these two processes have many of the same underpinnings as well as secondary challenges. And as shown here, you can see that they can feed on each other as well. When opioid use disorder and pain co-occur, they really can reinforce one another. And in order to effectively address one or the other, we really need to address them. And when we do, we can more effectively treat both pain and opioid use disorder. And as you can see here, not only do pain and opioid use disorder reinforce themselves, but many of the secondary consequences of pain and opioid use disorder reinforce themselves as well. So what is the underlying neurobiological mechanism we can use to explain this complex interaction between pain and opioid use disorder? This is actually, there's actually a lot that we are now starting to know about this process. So I'm going to spend the next several slides talking about some of the neurobiological basis that we now have come to understand and are understanding more and more over time. So for a long time, pain research really focused on how sensory systems change, how signals get amplified over time, these sensory signals get amplified over time. And that's still true and that still occurs, but growing research is that maybe that isn't true for patients who have persistent pain. In cases of persistent pain, sensory changes may become less important and the modifications and emotions and reward processing systems may actually take on more importance. And as this slide illustrates in fMRI data, at the beginning of an injury, so for subacute back pain, we really do see that this is a pain problem, this is a sensory problem. But after three months or as pain becomes more chronic, which we typically say is after three months of ongoing pain, persistent pain, the brain regions that are activated start to change. We start to see that parts of the limbic emotional system and the reward systems are really actually having a big impact on the pain and the pain experience. So what causes this shift? In order to understand this, it's helpful to actually talk a little bit about the neurobiology of reward and emotion and this is very elegantly described by Dr. Koob and Vilkoff in the Neurobiology of Addiction. And this is really Koob's life work. Things sort of you need to know about addiction. And as he says, thankfully addiction is sort of color coded for you. So you'll see that there are three different parts or stages of addiction that promote drug seeking. And the first part is this, the blue part or the basal ganglia and this is the binge intoxication system. And this affects motivation for a substance by changes in dopamine and opioid peptides. And we see that this also can play a key role in pain relief seeking and we'll talk a little bit more about that. So that's the actual, these are the systems that are involved in sort of drug use. The second system involved is the system of withdrawal and negative affect stage and this is the nucleus accumbens and the amygdala. And in this system we see that you get over time unfortunately loss of reward, dysphoria, pain and anxiety as it progresses and we start to withdraw from the substance and this causes this negative affective stage which is really in the nucleus accumbens and the amygdala. And the reward transmitters that we find are implicated in this, so in drug use we're getting positive hedonic effects from, as we talked about, increases in dopamine, opioid peptides, serotonin and GABA receptors. With ongoing use, which could be several months, which has been described by Dr. Volkow in fMRI data showing that after four months of repeated cocaine use we're seeing real huge changes in reward transmitters and reward transmitter helpers. So that over time you're getting negative hedonic effects of withdrawal and this is causing decreases of dopamine which can be felt as dysphoria, decreases of opioid peptides which can be felt as pain, decrease of serotonin which causes additional dysphoria, decrease of the GABA receptor causing anxiety and panic attacks. And so really what you're getting with this increasing system of this negative hedonic effects of withdrawal is you're getting a compromised reward system. But we also unfortunately know that it's not just the reward system that's compromised. There's also an opponent process that's going on and there are actually anti-reward transmitters that are facilitated in this process or recruited in this process. And these neurotransmitters are dynorphin which additionally causes dysphoria, the corticotropin releasing factor which causes stress, increases in norepinephrine which additionally cause stress. So these are really activated in the amygdala and the ventral striatum during withdrawal states and these can promote all of the symptoms that patients are having when they go into withdrawal. The third stage of addiction that promotes drug seeking is preoccupation or craving and this is really held in the basolateral amygdala and hippocampus. So in this system you're seeing there's a loss of executive functioning and decision making. This is leading to more impulsivity, compulsivity and sleep disturbance. So this is making drug use a more impulsive or compulsive behavior as opposed to something where there's a decision of whether to use or not. It actually takes over drug use so there really is lack of decision making and more activity on impulsive use. So how does this actually relate to pain? Because what we just talked about was really about substance use and what we're trying to understand is how we might see this type of process and how that relates to rewards and pain. And so there's a pain substance use researcher at Stanford named Jodi Trafton and she's helped to illuminate how closely intertwined the reward system that we just described is with pain. So let's look at it from her perspective. She boils it down to a three neuron circuit, the core of our reward learning circuit. And this system helps to predict opportunities for reward that tell us how we might be better in the next ten minutes than we are right now. And this system helps us find rewarding situations and then drags us into those situations. This system does not notice if our life will be better in ten minutes and worse tomorrow. It really doesn't have that type of decision making. It really is looking for a kind of immediate reward. And all of the neurons implicated in this system release dopamine. So the three neurons we're seeing is that there are dopamine neurons in the ventral tegmental area and this is part of our very primitive midbrain. And this helps detect opportunities that make our life better. Finding opportunities, making a guess of how much reward we would receive if we were acting. So it's really estimating the value of reward and really seeking opportunity. The nucleus accumbens pays a lot of attention to the ventral tegmental area and really listens to that area. And as it's receiving information from the VTA, it makes a decision of whether to do it or not. And when it makes the decision to act on a reward or act towards a reward, it tells the ventral striatum to go for that reward, that it's a worthwhile opportunity to take. The VTA also sends this information to the frontal cortex, which really helps determine long-term goals, not short-term goals. And because it's looking more towards the future, it processes things and it makes its own decision, but it does this in a relatively slow fashion. So in order for the ventral cortex to have control, the nucleus accumbens has to be really nice and slow. Also the ventral cortex can override the systems within the nucleus accumbens. This is actually very hard to do because really the nucleus accumbens is telling you to go for a reward right away, and the frontal cortex is not able to react soon enough. And the larger the dopamine input is in the system, the more likely you are to do the faster reward behavior. So what's the problem? Well, the reward system is crucial for survival. If it gets out of balance and starts to take over, it over-influences decisions. You can wind up in a behavioral state where you appear impulsive or driven by immediate gratification and unable to tolerate distress. And addictive drugs can put a lot of dopamine in the system, either by prolonging activity of neurotransmitters or increasing activity in these neurons. And so the search for quick pain relief can do the same thing. It actually puts a lot of dopamine into these circuits and ultimately can drive habitual compulsive relief seeking. So this is how we see that there could be a very clear relationship between drug seeking, which also dumps a lot of dopamine into these systems, as well as pain relief seeking. So let's think about this, if we were to think about an example of how you might see this in a patient who has pain. And we're going to use the example of the couch. So think about your back really hurting and the ventral tegmental area sees the couch and predicts that there's an opportunity for relief. And when it sees this opportunity, it sends a lot of dopamine into the nucleus accumbens area. And the nucleus accumbens says, this sounds really great. We should really go for it. We should go for that reward. And when you do that, your back pain immediately feels better and your brain recognizes that reward. It says, I got a reward. Your reward systems learn this and recognize that the couch, it's really a new context for pain relief. But in the same way with addiction, your next event laying down on the couch may not produce the same level of reward. So you seek something with higher immediate reward, maybe taking your patient's pain medication that can dump more dopamine in the system. So patients with pain and injury are going to start getting attracted to situations where they can get relief. The longer you have pain, the more you will get attracted to the things that give you quick relief, such as lying down, guarding, self-medication. This means that after injury, it's really a vulnerable time. People will start to orient to things that cause quick relief, but not necessarily recovery. And this is unfortunately a relatively unconscious reinforcing process. So if we have this, so what's happening over time? With time, we can see that there's this chronic dopamine firing that is actually reshaping many of our neurotransmitter circuits and making them very fast and hard to control. So just as we said that nucleus accumbens was working really quickly to be able to sense a reward and seek a reward, we know that that system is implicated by D1 receptors. And these are the receptors, the dopamine receptors in the nucleus accumbens that are telling it to act on reward, to decide to do behavior. And over time, with a large enough impulse, they will more continually fire. We also have D2 receptors, which you should sort of think of as the brakes in our system. And they are inhibited by dopamine. So increases in the level of activation, however, in order to, excuse me, however, in order to activate these, you really need to have a higher level of activation in order to have these dopamine receptors fire. So essentially, the D2 receptors are pushing back on the starting line so that it makes activation harder once you have the system, the high inputs into the D1 system. And in so doing, you can actually allow the frontal cortex time to step in and make a different decision. So ultimately, too much of this accelerator is a bad thing. When the dopamine receptors are chronically overactive, they can activate these D1 receptors and the D1 receptors become more efficient. They speed up decisions to seek quick relief. And you also get these activation of the anti-reward circuits, the dynorphin, the cortico-releasing factor, the norepinephrine. And this can increase our stress response, worsen our mood, amplify pain signals. And then in this way, pain severity can increase and relief-seeking behaviors can become impulsive and part of a vicious cycle. So what happened to the brakes or the D2 receptors, the inhibitory pathway? Well, these big spikes of dopamine that were exciting the D1 receptors caused these D2 receptors to be desynthetized and internalized. And they can't really work again until they're recycled and then we get new receptors synthesized. So you're ultimately sort of winding up a system that has no brakes. So what you're seeing is immediate relief-seeking, immediate pain relief-seeking, immediate potentially drug-seeking. So in summary, what we start to see is that pain relief-seeking can be an addiction-like state. So coupled with complex social, psychological, and biological stresses, certain people can become primed for the development of severe chronic complex pain and opioid use disorder. In both substance use disorder and pain relief seeking behaviors, can activate and overstress the reward system. So in both substance use disorder and pain, when the reward system is over activated, we get this anti-reward neurotransmitters in the limbic system, they get enhanced, they can cause stress, negative affect, impulsivity, they can induce compulsive behaviors that alleviate us feeling poorly. In both substance use and chronic pain, the executive function of the prefrontal cortex becomes impaired, unable to exert control over the ventral striatum and limbic systems, and can prevent activities that promote recovery. So what does this mean for chronic pain? Well, it kind of boils down in some ways to dysregulated dopamine. And we see that in rats, if you reduce dopamine receptors, rats will prefer opioids, they will look for more rapid ways to alleviate that, they will have more rapid withdrawal from noxious stimuli, more anxiety, they will have greater consumption of sugar water, going after rewards, any of the rewards that you would give them. And so this abnormally elevated dopamine levels may increase the likelihood that acute injury can lead to chronic pain in people who have these dysregulated dopamine systems. So as we're seeing the higher reward pathway with the abnormal reward pathway, we can see that in certain patients, they become in some way primed to develop or at more risk to develop chronic pain. We see that along with people who are using drugs that increase dopamine, their reward pathway is already dysregulated, and this can similarly lead to chronic pain or chronic pain relief seeking. People who are also activating the reward system, or patients who are using high doses of opioids, similarly can develop more or be at more risk to develop pain after an injury heal. Other implications, the addicted brain can amplify pain to justify a substance it craves. There can be alternating withdrawal and intoxication that can actually drive pain as well. So you get sympathetic and psychomotor activation that can worsen pain. Drug intoxication can mask pain and permit recurrent injury or overuse. And intoxication can impair adherence to pain treatment. So as you can see here, there are lots of different neurobiological processes going on in the brain that can actually make this so difficult to treat, and clinically is a lot of what we're seeing and why we struggle with patients who have both disorders. So which of our patients are with chronic pain or at most risk to develop an opioid use disorder? Well, we know that there are certain risk factors that have been established. And published rates of abuse or addiction in chronic pain populations range from four to 26%, though there's some argument that this may be higher in certain populations. And there are some known risk factors for opioid use disorder in the general population that we could use as pretty good predictors for patients who may develop problematic prescription opioid use. And these would be patients with any lifetime history of substance use disorder, which could include alcohol, tobacco, cocaine, or cannabis use. And we also know that genetic factors can play a role in putting a person at more risk for substance use. And so family history of substance use can also be a strong factor, as well as a history of legal problems, which could signify that the person has had a problem with their substance in the past. Heavy tobacco use also is a risk factor. So a patient who may have started smoking at a very young age or have a very heavy tobacco use history, history of severe depression, anxiety, or PTSD, all of these factors can lead to risks for development of opioid use disorder. Other principal risk factors we know are younger age. So people who are at younger age and develop pain are at more risk, as we said, previous substance use disorder. Certain pain conditions seem to be more primed for the development of an opioid use disorder, such as back pain, headache. And then as we spoke about, high use of chronic opioids, doses greater than 90 milligrams of morphine equivalents may also be a risk factor. We also know there are certain individuals that are more likely to be prescribed opioids. And these are patients who have a greater number of pain diagnoses, those with mental health and substance use disorders. And so in this way, you actually are getting an adverse selection. Those patients who are receiving opioids are actually those who are at more risk to develop a problem. And this is why we may be seeing so many problems in patients who are prescribed opioids because those who are receiving them are at the most, at the highest risk. And the concentration of opioid use among patients with chronic pain is quite concentrated. So about 5% of chronic non-cancer patients, excuse me, 5% of patients who have chronic non-cancer pain are using 70% of the total opioids that are prescribed. So there's really no other type of prescription medication that shows this degree of concentration among recipients. So again, this is another risk or sort of this adverse selection can be occurring. So why does it occur? Well, providers wanna help patients in pain and unfortunately, up until now, there have been few tools other than the prescription pad to help patients with pain. And patients with mental health and substance use disorders and multiple pain problems may be more distressed, have more pain and psychological symptoms as we described earlier. And they may more persistently demand opioid initiative dose increases to help avoid some of the symptoms they're having. And providers may write an opioid prescription sort of as a ticket out of the exam room to get out of the person with distress. But here we are again, sort of thinking about this population and thinking about what's going on and how do we determine if a person with pain has developed an opioid use disorder. And I think this situation brings up this clear question for us. How we think about addiction is this question or this picture on the left of someone using heroin or injecting heroin. And this is the picture on the right is how we think of dependence on pain medication. But are they really biologically any different? Is there really anything differently going on as we talked about before? And what we're starting to understand more based on all of the neurobiological information that we're now receiving and starting to know and understand is that really most likely most patients who are developing problems with opioids exist in this gray zone. It's probably not just addicted or not addicted. There are probably many of our patients who are prescribed opioids who actually exist on this continuum in this gray zone. And this slide sort of shows how the problem can also be on a continuum and how there can be different layers. So you can have your total pain population and within that population of patients you can have those who are having aberrant drug-relating behaviors. This may reflect what we previously called the misuse or abuse of a substance. And then there are your patients who may be misusing more or doing other behaviors. We would call this prescription drug misuse or misuse disorder and then you have your more severe opioid use disorder where you're really seeing the more severe consequences. But all of these behaviors really exist on a spectrum. So you may have patients who are self-medicating as we're calling chemically coping in order to treat symptoms of mood, sleep disturbance, traumatic memories. You can have patients who are using to prevent opioid withdrawal, patients using to receive a reward to get high, patients using because they have an addiction or patients using for diversion or for profit. And so medication or substance misuse by people with pain may occur for a lot of diverse reasons. It helps to identify if we can to address the driver of the misuse and then treat it. And we may be uncovering an opioid use disorder in some of these patients. This shows again just how problematic opioid use can exist on a continuum where a patient may first initially start having some mild indiscretion with their medication which may lead to some reward for the patient and this can then progress to potential repeated misuse which can then progress to opioid use disorder and then severe opioid use disorder over time. So what may start out as taking their medication slightly more as prescribed can sort of start this vicious cycle or perpetuate a cycle where patients can quickly develop more severe use disorders. And thinking about this, how this is different between people who are prescribed medication for pain treatment versus people who are prescribed for, or excuse me, people who are using recreationally. For a patient with pain who is dependent on the medication that's prescribed to them, the types of behaviors you might see in that patient are pestering or continually calling for early refills. Their narrative is that they are using this opioid to treat pain and the predominant symptom they have is pain and the predominant symptom of withdrawal they have is pain. A patient who is using heroin or another substance illegally, they're doing a lot of their behaviors are procuring opioids. So going to find an opioid, stealing to obtain opioids, those sorts of things. They're using paraphernalia, they have other behaviors that you're seeing and their predominant symptom of withdrawal is anhedonia. But ultimately, the same process goes on. You see social disruption, loss of control over use of the substance, controlled use despite, knowledge of harm and then craving. But for a patient who's prescribed pain medication, it's hard for them to understand that anything is wrong other than pain. They may have difficulty understanding because their symptom, the thing that they're feeling is pain, they may not be able to understand that they've developed a problem, may not have insight into that. The person who's using illicitly, using a substance that's illegal, typically has a bit more ability to accept that they may have a problem. And so although there are two different processes here, one person getting from a physician and another person not, ultimately, kind of they're leading to the same thing. And so ultimately, they're maybe not as different as we thought. But it's complex in opioid use disorder when we're talking about prescription opioid use disorder and that's because the patient is prescribed. Jane Ballantyne describes this in Archives of Internal Medicine saying that dependence on opioid pain treatment is not, as we once believed, easily reversible. It is a complex physical and psychological state that may require therapy similar to addiction treatment. Whether or not it is called addiction, complex persistent opioid dependence is a serious consequence of long-term pain therapy. And she describes in this graphic here how pain can increase over time based on distress and changes in tolerance and dependence and how this is all very interconnected, similar to the way it's interconnected for a patient with substance use disorder from an illegal substance. And so really, we've got these complex interactions going on which I think are made more complex because the patient has a belief and is using the substance for a symptom of pain relief seeking. But unfortunately, over time, what can happen, as we've been describing, is a different disorder can take over and that's the disorder of substance use or opioid use disorder. Which the diagnosis of which is actually here, listed here with the DSM-5 criteria which shows that, so this graphic shows how we used to call this or used to identify in the DSM-4 abuse versus dependence and we really made those two distinctions. But with the DSM-5, what we now have done is looked at this as a use disorder with different criteria, mild, moderate, or severe. And so as a patient, as we said, this sort of continuum or this gray zone, a patient having more than two criteria can actually fit a substance use disorder. It is important to note that for a patient prescribed opioids, withdrawal intolerance do not count for our DSM-5 criteria. However, the other types of factors you'll see are listed here and again, now they are listed as mild, moderate, or severe as opposed to differentiating them between abuse and dependence. In clinical practice, what you might see is what we call the four C's, loss of control, compulsive use, continued use despite harms, and craving. So as we just discussed, we no longer use abuse and dependence to diagnose an opioid problem. We now use what we consider to be the gold standard DSM-5 criteria. And this is as of 2013. So let's drill down a little bit about what we mean for this diagnostic criteria and what you would see in a typical patient. So what you would see are any of these 11 criteria, remembering that you're looking for two or more of these criteria in a 12-month period of time in order to make this diagnosis. Things you might see are opioids taken in larger amounts and over a longer period of time than intended. The patient may have a persistent desire or unsuccessful efforts to cut down or control their use. They will spend a great deal of time in activities necessary to obtain the opioid, use the opioid, or recover from the opioid effects. For patients who are struggling with a prescription opioid, this may be seen as multiple trips to an emergency department or other medical providers to obtain an opioid, potentially by legal or illegal means. Next, you might see craving, which we think of as a strong desire or need to use opioids. For patients who have pain, this is sometimes seen as increasing serious pain that is thought of more as like a pain craving. So a need to, a strong desire or need to treat that painful issue, but is really kind of thought of as more of a serious pain problem than a need specifically for opioids. Finally, you will see the other criteria listed here, which is the recurrent use resulting in failure to fulfill major role obligations at work, school, or home. Patients are probably not working. They may not be parenting. They may not be engaged in other functional activities in their life. Typically, they're continuing to use opioids despite having persistent or recurrent social or interpersonal problems caused or exacerbated by opioids. They're having important social, occupational, or recreational activities that are given up or reduced because of their opioid use. Again, a lot of lack of role fulfillment and functional activities. They might be using opioids in hazardous situations, such as driving under the influence of opioids, putting themselves in harm's way, being in an unsafe situation, prostituting themselves in order to obtain opioids. These would all be examples of hazardous situations. They may be continuing to use despite knowing that it's causing persistent or recurrent physical or psychological problems. This could be seen as a desire to continue taking an opioid despite having a serious opioid overdose or having worsening of anxiety or depression that was caused by the opioid. And then finally, you would see the two criteria of tolerance and withdrawal. Now, as I said before, it is important to recognize that if a patient is taking or is prescribed an opioid, taking that opioid as prescribed, no more, no less, then we actually do not count these criteria for a patient who is prescribed an opioid because we know that these factors are side effects of long-term prescription opioid use. However, if the patient is prescribed the opioid but they're taking the opioid more than prescribed, they're obtaining from multiple different prescribers, they're really using outside of the bounds of what is prescribed to them, we would count these criteria within our diagnosis of an opioid use disorder. So Tolerance is the idea that a patient is needing to take markedly increased amounts of opioids to achieve either intoxication or the desired effect. Really, they're having a markedly diminished effect with continued use of the same amount of opioids. In order to treat that, typically you're seeing the patient use more and more opioids over time to achieve a desired effect. Then finally, opioid withdrawal, which many of you probably have an understanding of what that is, which is marked by criteria that are on the clinical opioid withdrawal scale. Typically, we see patients are quite restless, irritable, anxious. They're typically diaphoretic. Their pupils are enlarged. They might have loose bowels or feel very nauseous or be vomiting. These are all signs of opioid withdrawal. It is very important that you as a provider, as well as your patients, understand that having opioid withdrawal in and of itself is not synonymous with having an opioid use disorder. Many patients and providers alike get confused by this point, which is that if you're taking an opioid for a long enough period of time at enough of a dose, say two weeks of oxycodone at 30 milligrams per day, if you abruptly stop that opioid, you may potentially go into opioid withdrawal. That's not because you've done something wrong or you haven't followed the prescription. It's because this is a known side effect, adverse effect of the medication that it can quickly develop physiologic dependence. The abrupt cessation can be experienced as opioid withdrawal. It's really important that you and your patients understand that just having opioid withdrawal in and of itself is not diagnostic of an opioid use disorder and doesn't mean that the patient needs to be treated with, say, certain treatments that we have for opioid use disorder. Clinical features that you would see would be potentially inconsistent healthcare use patterns, missed appointments, lack of engagement with non-medication treatment, signs or symptoms of drug use, either intoxication, overdose, track marks, emotional problems, psychiatric issues, potentially illicit drug use of other substances, problematic medication behavior, escalating doses, early refills, family concerns about use, functional stagnation or loss of functional roles, extreme difficulty with even a very slow opioid taper. The implications is that this is coming in a pattern or developing in a severity. You have to really determine the severity, determine the differential before you can give this diagnosis, but there are some features that make us concerned. This slide shows that there are certain behaviors that we think are less concerning than others. Requests for increased opioid dose is less concerning to us than other illegal activities such as forging prescriptions or selling an opioid prescription. That doesn't mean that the patient doesn't have opioid use disorder if they request an increase for an opioid dose, but we think that there's a differential associated with that. That that could be the patient is having increased pain from an acute pain process. You can see here that there are sort of yellow flags going to red flags where non-adherence with monitoring, not coming in for urine drug testing pill counts is a serious issue along with multiple lost or stolen opioid prescriptions and the illegal activities. These can be more indicative of a potential underlying opioid use disorder other than sort of non-adherence with recommended therapies such as physical therapy. If we think back about the patient that we described earlier, and remember this was a 35-year-old woman with chronic daily headaches and myofascial pain, severe depression, anxiety. She's been prescribed opioids for five years and she's really not been able to take care of her children and had worsening anxiety and function. She's also had a lot of history of some aberrant drug-related behavior. If we think about her and we think about does the patient, does this potential patient have, with chronic pain, have an opioid use disorder and well, does she meet the criteria? Well, has she been unable to fulfill major role obligations? Well, she actually hasn't been able to take care of her children at times so maybe, maybe that's a problem for her. Has she had social or interpersonal problems due to her use? Well, her family is concerned about her. She hasn't been able to work so again, a maybe. Has there been hazardous use? Is she using while driving, things like that? Another maybe. Again, tolerance and withdrawal do not apply in this situation because we've been prescribing the medication to her. Has she been taking the medication in larger amounts over a longer period of time than you'd hoped? Have you attempted to take her? Unsuccessful efforts to cut down or control the use, both maybes there. Is she spending a great deal of time to obtain the substance? She is calling you repeatedly, calling your office several times so that's a maybe or yes. Is she giving up important activities due to her use and has she reduced these activities? She's stating that she's not doing as much with her family, has lower quality of life. Is she continuing to use despite these harms? Potentially some of the harms that she's experiencing are due to her drug use and it's hard to know. Again, this complex interaction between pain relief seeking and drug seeking, there could potentially be some craving there. So for this, being able to apply the DSM-5 criteria to a patient such as this is complex and really kind of raises a lot of questions but in many ways you can actually see that we're not seeing symptoms we see for a patient who uses heroin but at the same time we're still seeing many of the same behaviors just in a slightly lesser extent. So if you were to evaluate this patient in your office to determine if potentially there was an opioid use disorder, what are you going to do or how are you going to approach this? Well, the first thing you're going to do is really normalize the process and as we've talked about in previous lectures, we're going to make this a part of universal precautions. So normalizing and saying, I evaluate the risks and benefits of these medications for all of my patients. I ask all of my patients to do urine drug testing and pill counts and things like that. I want to make sure none of my patients are being harmed by this medication. So really, this is a normal process, a normal thing that you are doing to make sure that your treatment is safe and effective. It's also important to appreciate that there can be a lot of fear and stigma associated with opioid use disorder, particularly for patients who have chronic pain. Recognize that the patient may come to you being quite fearful that you're going to abruptly stop their opioids, that you're going to tell them they need to taper, they might have a lot of anxiety and fear associated with that. So it's important to appreciate and empathize with that. So part of the evaluation first is to confirm and describe the chronic pain condition. What are you actually treating? Is there a diagnosis that's possible? Is there further evaluation that would potentially be beneficial or change the course? Is there worsening pain that you could potentially treat with medication or therapies that would be effective? You want to confirm if there has been any functional improvement with pain medication at all. If there's been no functional improvement, the patient is probably experiencing therapeutic failure of opioids. And if there's been no functional benefit and there's lack of opioid benefit, why would we continue opioids? You want to confirm and describe that appropriate treatment has been offered or failed. Are there treatments that can be optimized? Have non-medication options been tried or failed? You want to evaluate all of these things. You want to describe the patient's side effects from the medication, describe their relationship with their healthcare provider and any concerning behaviors. You want to describe their early refills, the refills from other physicians, describe their history, the lost medication, stolen medications, frequent ED visits. Certainly if their loved ones are concerned, you want to talk to them. Describe their substance use disorder history or current substance use history, if any. Patient may not be fully upfront with you about this, but it's important to ask. Describe any concomitant psychosocial factors, depression, sexual use history, adverse childhood experiences, marital financial job loss. You may consider checking a PHQ-9, a generalized anxiety disorder scale, pain catastrophizing scale, chronic pain self-efficacy scale. All of these can sort of help contribute to look at how has pain and potentially a use disorder affected this person's life. Diagnostically, it's important that you're obtaining a urine drug test. This would include an evaluation for alcohol use. You could consider getting an ethylglucuronide, which will tell you if the patient has used alcohol up to 92, or excuse me, 96 hours prior to coming in. We do have an entire lecture, part of a lecture that talks about urine drug testing in our risk assessment mitigation and management lecture, and I would encourage you to look into that. You may consider doing random pill counts, prescription drug monitoring, review of medical records, discussing the case with other prescribers or family members. There are some questionnaires you can use. None have necessarily been super well validated for this, but it can help identify patients who are at high risk for current barren drug-related behavior. So the current opioid misuse measure, a high score on this would raise concern for an opioid use disorder, but it's not diagnostic. There's also the screening tool for addiction risk, which is based on self-report and does correspond with the DSM-IV criteria. Both of these may be helpful if you're not sure exactly how to approach the situation or to get further information. But unfortunately, there's not one test or questionnaire that can confirm whether a prescription opioid use disorder is there or not. And so the initial PCP evaluation can provide more of a basis of the risk-benefit determination. And this initial evaluation will place the focus not only on concerning behavior, but also on pain and pain care. And it's important to recognize that you can have pain and an opioid use disorder, but that treating pain with opioids in the setting of an opioid use disorder can be very risky and potentially harmful. And that treating opioid use disorder without treating pain is also not likely to be very effective. So based on your initial evaluation, if you're concerned that both are occurring, you may consider referral for diagnosis if you don't feel comfortable making the diagnosis, or ultimately you could make the diagnosis yourself based on that DSM-V criteria that we talked about before. So what next? Well, you're making ultimately a risk-benefit ratio judgment of the treatment, not of the patient. Do the benefits of prescribing this patient opioids outweigh the risks? That's the question you're asking yourself. If the risks outweigh the benefit, you're referring the patient and stopping or tapering opioids. You certainly want to continue to treat the person's pain with non-opioid treatments, which may also be non-medication treatments. And if you do undercover, the patient has an opioid use disorder, it's important to help them seek effective treatment, such as medication-assisted treatment. A quick word about that. So there are three FDA-approved medications for the treatment of opioid use disorder, naltrexone, methadone, and buprenorphine. Naltrexone is an opioid antagonist, possible pain relief at very, very low doses. There's new emerging data about that, but it probably will not work very well for patients who have chronic pain because you're basically blocking the opioid receptors. Methadone is a full opioid agonist with analgesia list lasting about four to six hours. Its treatment of opioid use disorder lasts 24 hours. It can only legally be dispensed through a federally qualified opioid treatment program for the treatment of opioid use disorder. Buprenorphine is a partial opioid agonist. Its analgesic properties last about four to six hours. It can be dosed twice a day or three times a day if you're hoping to improve pain. And it can be utilized to help patients taper off of opioids as well. You do need to have a DEA waiver or an X license in order to prescribe this in the office. It can also be dispensed through a federally qualified opioid treatment program. You can absolutely find more information about this through the PCSS MAT program, and I encourage you to look into that if you have any questions. So back to this case. This patient that we were talking about before, she undergoes a full opioid use disorder assessment, and she is determined based on the assessment to have moderate opioid use disorder based on her failure to fulfill roles in her life, continued use despite harms, time spent patient and craving. She is reluctant and scared to consider alternative treatments or seek opioid use disorder treatment, but she's appreciative of the honest assessment of her condition, and she would like to think about the idea. Two weeks later, she makes an appointment to see you and seeks treatment for her opioid use disorder. Three months after stabilizing and starting buprenorphine naloxone along with cognitive behavioral therapy, she says, thank you so much for helping me. I am myself again. I am finally enjoying my life with my kids, and I'm thinking about starting a small business. So this is a patient who was clearly suffering not only from pain, but from an opioid use disorder, and treatment for her was remarkable and life-changing. So this was a patient where it was the most compassionate thing you could do to diagnose her with this condition and treat her condition in order to help her have a better quality of life. So if we think about those questions, does this patient have pain? Yes, she absolutely has pain. She has migraines, and she has other myofascial pain disorder. Does she have an opioid use disorder? Yes, she does based on our evaluation of the DSM-5 criteria, giving her a diagnosis of a moderate opioid use disorder. What factors place this patient at risk for an opioid use disorder? Well, there were certain personality traits she had that placed her at risk, her younger age and her young age of an opioid initiation, her concomitant use of benzodiazepines, which could potentially be somewhat synergistic or lead to cross-addiction and dependency. There was mental illness, which was placing her at a greater vulnerability for chemical coping or using the substance to treat something other than pain. She had very severe adverse childhood experiences, which made her very vulnerable. She had a history of medication non-adherence. She was losing prescriptions, and so that signified that she was potentially having some compulsive use, seeking those very quick rewards. There were possible frequent bouts of opioid withdrawal from overuse of opioids, and this could have been leading to that negative affective state that was changing her motivation and causing drug craving. What can you do to help this patient? Well, identifying those underlying biopsychosocial factors that were contributing to her pain were important. Identifying the neural processes that were potentially contributing to her behavior, again, that potential for withdrawal, causing changes in motivation and craving, guiding her towards activities and treatment modalities that are kind of resetting her neurobiological, the changes that are occurring in her brain. So how can we increase those D2 receptors, those receptors that help put on the brakes so that we can change the reward seeking? The way that we can do that is with lower levels of dopamine input, so limiting the use of addictive drugs or medication, tobacco, fast-acting analgesics, having social reinforcement, getting her reengaged with her family, getting her back into the workforce, doing things like that, helping her be more effective in her problem solving, helping improve her effective emotional coping through cognitive behavioral therapy and other types of therapy, small goal achievement, her being able to now care for her children again, to be able to care for herself, are all reinforcing in a positive way, and improving her quality of life or engagement with life. All of these things will help guide her more towards the safer, more effective forms of pain treatment that ultimately will serve her lifelong. Part of getting her out of that cycle was really offering her safe and effective treatment of her condition, which was both pain and opioid use disorder. So in conclusion, chronic pain and substance use disorder share many common features that can motivate behaviors. Diagnosing opioid use disorder during pain treatment is difficult and requires a thorough evaluation. Typical substance abuse risk factors probably apply to prescription opioid use disorder, and we know that higher risk groups are those who are younger, using tobacco with comorbid psychiatric conditions, or using higher doses of opioids. Managing opioid use disorder by referring to substance use treatment and considering medication-assisted treatment like buprenorphine or methadone is absolutely safe and appropriate. Our references are listed here, along with some information about the PCSSO Colleague Support Program and LISTSERV, and some information about PCSSO. Thank you so much for your attention. Have a great day.

opioid use disorder

chronic pain

assessment

neurobiological framework

risk factors

reward and emotion processing systems

comprehensive evaluation

medication-assisted treatment

buprenorphine

methadone